Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Wounds and Injuries

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasm Metastasis

Fractures, Bone

Bone Marrow Diseases

Spinal Fractures

Fractures, Compression

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Neoplastic Processes

Spinal Injuries

Back Injuries

A bilateral approach is chosen to insert working cannulas into the posterior part of the vertebral body through a posterior transpedicular approach.Once inserted, the balloons are inflated using visual, volume and pressure control to create a cavity.The balloons are then deflated and removed. The Bone Filler Device is then advanced through the working cannula towards the anterior part of the cavity and cement is slowly extruded by a stainless steel stylet, acting as a plunger. When the amount of cement from the first Bone Filler Device is delivered in the cavity, it is removed and another Bone Filler Device is advanced through the working cannula.

balloon kyphoplasty

Jean-Denis LAREDO, M.D.,PR.

Antoine FEYDY, M.D., PhD

Balloon Kyphoplasty is an alternative to vertebroplasty in the treatment of painful malignant vertebral fractures. This is a mini-invasive percutaneous treatment, aiming to stabilize the vertebral fracture, decrease of pain. This technique also improves patient function. Namely, bedridden patients are often able to resume walking in the days following vertebral cement injection. Advantage of Balloon Kyphoplasty as compared to vertebroplasty is the ability to inject the cement into the diseased vertebral body which shows cortical destruction with lower pressure, thereby possibly reducing cement leakage and related complications.

This is a multicentric, observational prospective study. Patients are evaluated before and after the procedure.

Sixty women or men older than 18 years, with 1 to 3 painful vertebral fracture(s) of malignant origin (due to multiple myeloma or osteolytic vertebral metastasis) will be enrolled. Each patient will be followed during 1 year after the procedure with 7 visits at D-8, D-1, D1, D15, D90, D180, and D360 or until the death of the patient.

The main evaluation outcome is patient self-global satisfaction regarding the procedure on a semi-quantitative satisfaction scale, 15 days after the Balloon Kyphoplasty.

Vertebral compression fractures (VCF) represent an important source of morbidity in patients presenting osteolytic metastatic or myelomatous vertebral involvement. In addition, cancer treatments may induce osteoporosis with an additional risk of vertebral fractures.

* Current medical treatments are symptomatic. They do not treat the fracture itself.
* Vertebroplasty is an interventional radiological technique that consists of injecting, percutaneously, acrylic cement into the fractured vertebra under radiological guidance and local or general anaesthesia, in order to combine two effects: stabilization of the vertebral body fracture and pain reduction.
* Balloon Kyphoplasty is a variant of vertebroplasty which is performed using the KyphX® System (Medtronic., Sunnyvale, California). Balloon kyphoplasty aims at restore vertebral height of the fractured vertebra using an inflatable balloon prior to inject surgical polymethylmetacrylate (PMMA)cement,into the vertebral body to fix the fracture. It is an expensive technique costing around 4,000 euros for up to 2 vertebrae in the same patient. The surgical technique for the procedure has been described by LIBERMEAN et al: A bilateral approach is usually chosen to insert working cannulas into the posterior part of the vertebral body through a posterior transpedicular approach. In case of limited and asymmetric vertebral destruction, a single unilateral approach may be preferred. Fluoroscopy is used to insert the tools and control the procedure. With reaming tools, two working channels are created and the balloons are inserted. The balloons are available in lengths of 10, 15 and 20 mm.

The two balloons (one on each side) should ideally be centered at middle height between the superior and inferior endplates and in the anterior two-thirds of the vertebral body. Balloon placement into the vertebral body is checked using radiopaque markers at the two extremities of the balloon. Once inserted, the balloons are inflated using visual, volume and pressure control to create a cavity. Inflation is stopped when one of the following inflation endpoints is reached: pressure raised over 400 psi, balloon contacts one of the cortical bone of the vertebra or reaching maximal balloon inflation volume. The balloons are then deflated and removed. The mean balloon inflation volume is 2 to 3ml. The Bone Filler Device, filled before with 1.5 ml of PMMA, is then advanced through the working cannula towards the anterior part of the cavity and cement is slowly extruded by a stainless steel stylet, acting as a plunger. When the amount of cement from the first Bone Filler Device is delivered in the cavity, it is removed and another Bone Filler Device is advanced through the working cannula. This step is repeated till a complete fill of the cavity is obtained. The same procedure is repeated through the other working cannula at the contra-lateral pedicle. Filling of the cavity with highly viscous PMMA is performed under continuous fluoroscopic control.

The aim of this study is to quantify the analgesic and patient function improvement of Balloon Kyphoplasty together with complication types and rate in patients with malignant vertebral fractures due to metastatic disease or multiple myeloma.

Treatment of Malignant Vertebral Fractures With Percutaneous Balloon Kyphoplasty.

Assessment of Percutaneous Balloon Kyphoplasty in the Treatment of Malignant Vertebral Fractures (Multiple Myeloma and Osteolytic Metastases) : "Observational Study"

Assistance Publique - Hôpitaux de Paris

Musculoskeletal Diseases

Spinal Diseases

Central Nervous System Depressants

All Drugs and Chemicals

Bone Density Conservation Agents

Anesthetics

Anesthetics, General

Diphosphonates

Sham Procedure \& Conservative Treatment

Subjects will be blinded and randomised to Arm 1 and will undergo a general anaesthetic and undergo a sham procedure. They will also be treated under conservative management alone.

Below is a list of the conservative management they will be managed by their Doctor:

1. Bisphosphonates
2. Pain relief
3. Systemic chemotherapy for Myeloma disease
4. Bed rest
5. Radiotherapy
6. Physiotherapy

This is a non interventional as conservative treatment (standard of care for multiple myeloma patients) is used.

Balloon Kyphoplasty \& Conservative Treatment - Interventional Arm

Subjects will be blinded and randomised to Arm 2 (balloon kyphoplasty) and will undergo a general anaesthetic and undergo a balloon kyphoplasty surgical procedure. They will also be treated with conservative management.

Below is a list of the conservative management they will be managed by their Doctor:

1. Bisphosphonates
2. Pain relief
3. Systemic chemotherapy for Myeloma disease
4. Bed rest
5. Radiotherapy
6. Physiotherapy

This is a interventional arm (balloon kyphoplasty procedure) and the patient will receive conservative treatment (standard of multiple myeloma patients) is used.

Arm 2 Balloon Kyphoplasty (Medtronic LCC) and Conservative Treatment

Subjects will be blinded and randomised to Arm 2 and will undergo a general anaesthetic and undergo a balloon kyphoplasty surgical procedure. They will also be treated with conservative management.

Below is a list of the conservative management they will be managed by their Doctor:

1. Bisphosphonates
2. Pain relief
3. Systemic chemotherapy for Myeloma disease
4. Bed rest
5. Radiotherapy
6. Physiotherapy

Arm 2 Balloon Kyphoplasty

Patients recruited to Arm 1 and Arm 2 will undergo conservative management for Multiple Myeloma recommended by their Consultant Hematologist.

* Concomitant treatment with bisphosphonates
* Pain relief as required
* Systemic chemotherapy for Myeloma disease
* Bed rest
* Radiotherapy
* Physiotherapy

Conservative Management

Chara Kyriakou, MD PhD

Sean Molloy, FRCS MSc

The purpose of this study is to determine whether surgical treatment, balloon kyphoplasty is more effective compared to conservative treatment alone (sham procedure) when assessing clinical, translational, radiological \& patient outcomes in patients with multiple myeloma.

Subjects will be recruited to the study if they have VAS score ≥ 6 and has given informed consent to participate in the Melody Study will be randomised to Arm 1 Sham Procedure and Conservative treatment or Arm 2 Balloon Kyphoplasty and Conservative treatment. Subjects recruited to Arm 1 (Sham Procedure and Conservative treatment) can cross over into Arm 2 (Balloon Kyphoplasty and Conservative Treatment) if they have a VAS score ≥ 6 between 8-12 weeks.

Multiple myeloma (MM) accounts for 10% of the malignant haematological diseases and approximately 1% of all cancer-related deaths in Western countries. MM is characterised by the accumulation of malignant plasma cells in the bone marrow leading to impaired haematopoiesis and the highest incidence of bone involvement among the malignant diseases. MM bone disease is the result of increased destruction of bone that cannot be compensated for by new bone formation. Approximately 80% of patients with MM develop skeletal complications including bone pain, hypercalcemia, osteoporosis, osteolytic lesions and pathologic fractures. Vertebral fractures may be associated with spinal cord compression and neurological complications requiring surgery and/or radiotherapy. Osteolytic bone destruction is the most debilitating manifestation of MM, has a severe impact on patients' quality of life and is responsible for increased morbidity and mortality. Furthermore, bone resorption activity has been shown to be an independent risk factor for overall survival in patients with symptomatic MM. Moreover, myeloma-associated lytic bone lesions do not repair, even in patients who are disease free for years.

More than 50% of patients develop vertebral compression fractures (VCFs) either by the time of diagnosis or during the course of the diagnosed disease. These fractures can compromise the spinal cord and patients' height and stature, cause angulation of the spine, increasing sternum pressure, eventually resulting in sternal fractures and compromising the pulmonary capacity. 9% loss in predicted forced vital capacity is associated with each vertebral fracture. Deformity, Insomnia, depression, substantial physical, functional and psychological impairment and ultimately disability can be the result of severe vertebral compression fractures poorly managed at presentation.

Management of spinal MM bone disease

1. Bisphosphonates he use of bisphosphonates, which inhibit bone reabsorption, for the treatment of MM bone disease has led to an improvement in the quality of life for patients with MM.
2. Conservative (non-surgical) management (this is standard of care management for patients with multiple myeloma)

   1. Pain relief
   2. Systemic chemotherapy for Myeloma disease
   3. Bed rest
   4. Radiotherapy
   5. Physiotherapy
3. Standard surgical procedures

A. Open surgical decompression Anterior or posterior decompression and stabilisation through internal fixation hardware and bone grafting (in \<0.5% with gross spinal deformity or neurologic impairment). Higher morbidity and mortality in MM patients because of comorbid conditions related to age, disease associated end-organ damage and immunosuppression B. Minimally invasive - Cement Augmentation

1. Percutaneous Vertebroplasty
2. Percutaneous Kyphoplasty (i.e. Balloon Kyphoplasty)

COST BURDEN, HEALTH ECONOMIC IMPACT AND COST UTILITY ANALYSIS There is little evidence on differences across health systems in choice and outcome of multiple myeloma being treated with conservative treatment, chemotherapy and spinal surgery are three of many treatment options for managing multiple myeloma. The true cost associated with current therapies in addition to supportive care, is significant and poses a tremendous financial burden to both patient and health care providers.

There is therefore a need to begin to systematically optimise the guidance for treatment for this subgroup of patients especially when comparing the two treatment arms in this study, conservative treatment alone versus surgical treatment, balloon kyphoplasty.

This study will determine the cost burden, health economic impact and cost utility analysis by combining the quality of life measurements, the cost analysis will allow a calculation of the relative cost-effectiveness of conservative treatment standard of care versus standard of care plus balloon kyphoplasty.17

RATIONALE FOR CURRENT STUDY

Osteolytic lesions of vertebral bodies are frequent problems in multiple myeloma patients predisposing to severe pain, vertebral fractures and consequent neurological complications.Open surgical procedures to stabilise or correct deformed vertebral bodies are associated with major complications in this group of immunocompromised patients. In addition, open procedures are often not possible, due to a severely impaired strength of the bone tissue, which does not allow the safe application of screws and plates. As a result the standard management to reduce the local pain secondary to vertebral compression fracture has for many years been with pain relief, radiotherapy and the other elements of conservative management listed above. The development of minimally invasive procedures such as kyphoplasty and vertebroplasty has been demonstrated to be an additional effective treatment option to improve mobility and quality of life and to reduce pain.

Percutaneous vertebroplasty involves the injection of acrylic bone cement into the vertebral body in order to relieve pain and/or stabilise the fractured vertebrae and in some cases, restore vertebral height.

Percutaneous Kyphoplasty (or Balloon Kyphoplasty) is performed by inserting a balloon-like device (inflatable bone tamp) through a channel created by a hand drill in the fractured vertebrae. The tamp is positioned and inserted into the vertebral body. The balloon is then inflated slowly until normal height of the vertebral body is restored or the balloon reaches its maximum volume. The procedure is intended to restore vertebral height and correct kyphosis. It may also help to improve pulmonary and gastrointestinal function and reduce the likelihood of subsequent vertebral compression fractures. The inflation of the balloon tamp creates a cavity in the vertebral body so that when the bone tamp is withdrawn, bone cement can be injected into the cavity at a lower pressure, potentially reducing the risk of cement leakage. The cement increases the strength of the vertebra and is intended to provide pain relief.

To Compare Conservative Management Vs. Balloon Kyphoplasty in the Treatment of VCFs in Patients With Multiple Myeloma

Multiple Myeloma Spinal Disease Study; A Multi-centre, Prospective, Single Blinded, Randomized, Controlled Study to Compare Conservative Management Alone Vs. Balloon Kyphoplasty With the Treatment of VCFs in Patients With Multiple Myeloma

Data collected for all intervention groups from the study will be assessed to compare the overall cost of care for conservative management vs. kyphoplasty

Royal National Orthopaedic Hospital NHS Trust

Head of Research Innovation Centre

Nervous System Diseases

Syndrome

Low Back Pain

Back Pain

Pain

Failed Back Surgery Syndrome

Neurologic Manifestations

Postoperative Complications

Chronic Graft Versus Host Disease

Oculocerebral Syndrome With Hypopigmentation

Adjuvants, Anesthesia

Analgesics

Pharmaceutical Solutions

Bupivacaine

Fentanyl

Anesthetics, Local

Analgesics, Opioid

Narcotics

Anesthetics, Intravenous

Continuous intrathecal prognostic infusion test of active solution: intrathecal bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml

6 hour washout followed by

Continuous intrathecal prognostic infusion test of inactive placebo solution: preservative-free normal saline

Continuous intrathecal prognostic infusion test of inactive placebo solution: preservative-free normal saline

6 hour washout followed by

Continuous intrathecal prognostic infusion test of active solution: intrathecal bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml

The patient is infused with solution through the percutaneous intrathecal catheter at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours

Continuous intrathecal prognostic infusion test

Bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml continuous infusion at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours

Intrathecal infusion of normal saline at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours

Placebo

40-mL IDDS containing a solution of fentanyl 50 mcg/mL with bupivacaine 30 mg/mL

Intrathecal Drug Delivery System (IDDS)

Salim Hayek, MD

The purpose of this study will be to determine the efficacy and the prognostic value of a continuous intrathecal prognostic infusion test in an in-hospital setting for selecting patients who would have better long term outcomes for treatment with intrathecal implantable devices. The investigators will compare the primary outcomes \[changes in pain intensity score (NRS), patient global impression of change (PGIC)\] before and after intrathecal infusion of an admixture of bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml versus normal saline.

The study will include 36 patients with intractable chronic low back pain in the setting of lumbar post-laminectomy syndrome or vertebral compression fracture who failed conservative management and are considered candidates for IDDS.

Prior to the implant, the patients will undergo an intrathecal prognostic infusion test with an externalized catheter. Baseline NRS pain scores will be assessed and documented on all patients upon admission to the preoperative area. An intrathecal catheter will be placed in the outpatient procedure suite at the appropriate level for target dermatomes. The needle entry point will occur in the upper lumbar spine and catheter tip will be placed in the lower thoracic spine, under local anesthesia with the patient awake and with minimal or no sedation. The intrathecal infusion will be started using an external pump once patient is in the PACU. The research component is to perform the intrathecal test with normal saline (inactive placebo solution) in addition to a test with fentanyl and bupivacaine (active solution). Patients will be randomly assigned to either Group I (continuous infusion of bupivacaine and fentanyl followed by saline) or Group II (continuous infusion of saline followed by bupivacaine and fentanyl).

In PACU, patients will be started on an infusion rate of 0.5 ml/hr and titrated to pain relief greater than 50% of baseline or up to 0.8-1.0 ml/hr within 6-8 hrs after start of the infusion. A clinician blinded to the treatment arm will assess NRS and PGIC on the patients after approximately 12 hours. Assessment will include changes in pain intensity score at rest and upon ambulating or performing maneuvers that normally elicit patient's low back pain. A 4-6-hour washout period will be allotted with infusion of preservative-free normal saline at a rate of 0.2 ml/hr, after which the physician will document a return of the NRS to baseline before switching therapies.

Recruitment: Subjects will be recruited from patients seen at the University Hospitals Pain Medicine clinics by attending physicians. Screening will be done before obtaining consent by an investigator. If patients are deemed appropriate for an intrathecal device they will undergo normal procedures and guidelines in place prior to being considered candidates for an implantable device. No subject will be compensated for participation.

Consent Process: Subjects will be consented by one of the investigators. An explanation in lay terms for the reasons of the study and the proposed prognostic benefits will be used to promote patient understanding. If interested, eligible individuals will be given the opportunity to ask and have all questions addressed before signing the informed consent document. The procedure will occur at their next visit, and continued consent of study participation will be confirmed.

Study Design: This is a randomized, double-blind, placebo controlled cross over study comparing prognostic intrathecal testing with an admixture of bupivacaine and fentanyl versus saline. None of the procedures in this study deviate from usual clinical care that patients receive at UHCMC or nationally. Baseline scores using the numerical rating scale (NRS) for pain (a scale form 0-10, where 0 signifies no pain at all, and 10 the worst possible pain) will be recorded, both in the sitting or supine position (least pain) and with ambulation or standing (worst pain). Patients will be given weight based cefazolin (or vancomycin if indicated) prior to placing the externalized intrathecal catheter. Placement of the percutaneous intrathecal catheter will be done in the operating room with minimal or no sedation in the prone or lateral decubitus position under fluoroscopic guidance. Needle entry will occur in the mid-upper lumbar spine and through the needle an intrathecal catheter will be advanced until its tip is positioned in the posterior intrathecal space in the lower thoracic spine. The needle is then removed and the catheter is secured in place with steri-strips and a clear sterile bio-occlusive dressing will be placed. Patients will then be transferred to the PACU where they will be initiated on one of two solutions that will be prepared for each patient by the investigational pharmacy staff at UHCMC. The solutions will be labeled as "Intrathecal solution 1" and "Intrathecal solution 2" and will be contained in a sterile 50 ml bag. Solution 1 and 2 may contain either:

1. Preservative-free normal saline
2. Fentanyl 1 mcg/ml and bupivacaine 0.625 mg/ml

The content of Intrathecal solution 1 and 2 will be unknown to all investigators and participants in the study with the exception of the investigational pharmacy. The order of the Intrathecal solution (1 or 2) will be determined by pharmacy using a computer generated random sequence allocation. The intrathecal catheter will be attached to a pump delivering solution 1 or 2 at around noon time, in the recovery area on the day the catheter is placed. A bolus of 1cc will be given through the infusion pump at initiation of therapy and the patient will then be started on an infusion rate of 0.5 ml/hr. After 3-4 hours (around 3-4 pm) and similarly around 6-7 pm the rate will be titrated depending on patient's response up to a maximum of 0.8-1.0 ml/hr. If the patient has achieved \> 50% pain relief compared to baseline, no up-titration will occur; i.e. the rate will be increased only if the patient has not had 50% or more reduction in baseline pain on the NRS. The intrathecal rate will be kept the same provided the patient had 50% or greater decrease in pain scores or has reached the 1.0 ml/hr rate (whichever comes first). The rate will be unchanged from 6-7 pm until around 6-7 am the next morning when the infusion will be stopped and the patient will be assessed for pain relief. In the morning, the patient will be asked to rate the pain score at rest (in bed or chair) and with ambulation/standing. The pain scores will be recorded and the catheter will be aspirated at the hub to ensure continued cerebrospinal fluid flow and the patient will be started on a solution of preservative-free normal saline at 0.2 ml/hr to keep the catheter patent. After 6 hours, around noon time, the patient will be crossed over to Intrathecal solution 1 or 2, depending on what she/he had the day before, given 1.0 ml of that solution as a bolus and then infusion will be started at 0.5 ml/hr and the same protocol as the day before will be repeated with the patient discharged the next morning. Patients who experience greater than 50% pain relief (relative to baseline) with either intrathecal solution will be offered the implant of a permanent IDDS that will deliver a combination of bupivacaine and low-dose fentanyl. Patients not responding to both solutions with greater than 50% pain relief will be considered to have failed the intrathecal test and would not proceed to implant. The patients will be asked to pick which solution provided better pain relief: solution 1 or solution 2 and responses will be recorded. Additionally, pain scores obtained periodically as part of patients' usual clinical care vital signs and recorded by the nursing staff on the hospital ward will be collected throughout the study. Un-blinding for patients who had a successful intrathecal prognostic infusion test with greater than 50% pain relief will not occur until 12 months have elapsed since the pump implant.

Outcome measures will include:

1. Baseline prior to commencement of the prognostic infusion test: Pain intensity using the Numerical Rating Scale \[NRS\], patient global impression of change \[PGIC\], Oswestry disability index \[ODI\] and painDETECT.
2. At 14-18 hours: Pain intensity in Numerical Rating Scale \[NRS\], patient global impression of change \[PGIC\], complications and side effects.
3. Prior to second infusion: Pain intensity in Numerical Rating Scale \[NRS\], patient global impression of change \[PGIC\], complications and side effects.
4. At prognostic infusion test completion: Pain intensity in Numerical Rating Scale \[NRS\], patient global impression of change \[PGIC\], complications and side effects, Oswestry disability index \[ODI\] and painDETECT.
5. At 6 and 12 months post-implant for implanted patients Pain intensity in Numerical Rating Scale \[NRS\], patient global impression of change \[PGIC\], Oswestry disability index \[ODI\] and painDETECT.

Study Methodology/Procedures: The study will include 36 patients with intractable chronic low or mid back pain due to failed back surgery syndrome or vertebral fracture who failed conservative management including epidural steroid injection and medical therapy and were referred to our practice for pain management.

Patient will undergo the usual psychological and medical evaluations before the initiation of the prognostic infusion test. Patients who are considered candidates for intrathecal pump implant fulfilling the inclusion/exclusion criteria above and who elect to participate in the study will be randomly assigned to two groups.

Group I tested with continuous infusion of intrathecal bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml for 14-18 hours followed by a trial with normal saline for another 14-18 hours.

Group II tested with intrathecal normal saline for 14-18 hours followed by intrathecal Bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml for another 14-18 hours.

Note that drugs will be delivered by the pharmacy to a blinded physician and labeled as Intrathecal solution 1 and Intrathecal solution 2 to be administered sequentially, separated by a 4-6-hr infusion of preservative-free saline.

Outcomes will be assessed and documented on all patients upon admission to the preoperative area. The patients will be taken then to the procedure room and a standardized intrathecal catheter will be placed under fluoroscopic guidance where the tip of the catheter will be placed at the T7-T11 posterior intrathecal interspace. Patients will be discharged to the PACU where they will be started on a rate of 0.5 ml/hr.

Six to eight hours following initiation of the infusion, all the patients will be titrated to 0.8-1.0 ml/hr, provided less \< 50% improvement in pain scores occurs. A physician who is blinded to the treatment will assess NRS after approximately 12 hrs (around 6-7 am of the following day). A 4-6 hours washout period will ensue with infusion of preservative-free normal saline at a rate of 0.2 ml/hr after which the physician will document a return of the NRS to baseline before switching therapies or record the value at 6 hrs after infusing normal saline and switch then to solution 2. NRS will be reassessed around 6 am the following morning. Additionally, pain scores documented with usual clinical care vital signs will be captured. All reported adverse events will be recorded.

No pain medications will be prescribed during the admission. If such medications are needed, the patient will be excluded from continuing on with the study and will be recorded as a prognostic-infusion-test failure.

The intrathecal catheter will be aspirated for confirmation of free cerebrospinal fluid flow (about 1 ml) between all solution changes and at the end of the prognostic infusion test.

After the completion of the prognostic infusion test, the catheter will be removed and patients will be discharged home.

Only patients who report \>50% reduction from baseline NRS while receiving either intrathecal solution will be considered for intrathecal drug delivery system implant. It is conceivable that some patients may get \>50% reduction in pain scores with both the active solution and saline or have better outcome with the saline solution. The patients will be asked to answer a binary question rating preference to solution 1 vs. solution 2. Patients with pain relief greater than 50% will be implanted with an IDDS and will receive an intrathecal solution of fentanyl and bupivacaine. All subjects with \>50% pain relief with either or both intrathecal solutions will be implanted. Even if the patient gets \>50% pain relief only from the saline solution, or the patient chooses the saline solution over the active solution (when asked if #1 vs. #2 was better relief) each patient will receive active drug after being implanted. All patients will be compared in long-term outcome (secondary outcome measures) at 6 months and 12 months versus the response to the prognostic test solutions.

Unblinding of solution 1 and 2 will not occur until 12 months have elapsed since pump implant. The six and twelve month visits will be coordinated with a pump refill visit.

Data Collection: Randomization will be performed, and baseline data will collect on admission to the preoperative area. A physician or physician assistant will obtain all data.

Baseline data collected will include name, last 4 digits of social security number, age, sex, race, duration of pain, treatment group, average 0-10 low back numerical rating scale (NRS) pain scores over the past week and analgesic medication consumption.

The primary outcome variable will be the change in pain intensity score \[NRS\] 0-10 numerical rating scale back pain score at the end of the intrathecal prognostic infusion testing period around 6am between Intrathecal solution 1 and Intrathecal solution 2.

Secondary outcome variables will be Oswestry disability score, changes in painDETECT, Patient Global Impression of Change (PGIC) and side effects (medications) and complications (injections). These variables will be recorded at baseline, at the completion of each phase of the prognostic infusion test, and at 6 and 12 months post-implant.

Patients who are considered candidates for intrathecal pump implant fulfilling the inclusion/exclusion criteria and who elect to participate in the study will be randomly assigned to two groups:

Group A tested with continuous infusion of intrathecal bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml for 14-18 hours followed by a trial with normal saline for another 14-18 hours; separated by a 4-6-hr infusion of preservative-free saline.

Group B tested with intrathecal normal saline for 14-18 hours followed by intrathecal Bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml for another 14-18 hours; separated by a 4-6-hr infusion of preservative-free saline.

The drugs will be delivered by the pharmacy to a blinded physician and labeled as Intrathecal solution 1 and Intrathecal solution 2 to be administered sequentially, separated by a 4-6-hr infusion of preservative-free saline. The content of Intrathecal solution 1 and 2 will be unknown to all investigators and participants in the study with the exception of the investigational pharmacy. The order of the Intrathecal solution (1 or 2) will be determined by pharmacy using a computer generated random sequence allocation.

Determining the Prognostic Value of Continuous Intrathecal Infusion

A Randomized Double Blind Cross-over Trial of Continuous Intrathecal Infusion for Assessing Patients With Chronic Non-cancer Pain Who Would Benefit From Treatment With Intrathecal Drug Delivery System (IDDS) Implant

Numerical Rating Scale is an 11-point pain scale whereby 0 signifies no pain and 10 the worse pain ever

Oswestry Disability Index (ODI) This scale based on a questionnaire of activities measures the impact of pain on multiple factors within a patient's daily life. Higher values represent worse outcomes, or a higher impact from pain on the patient's daily life. The total score range is 0-50. Subcategories include: 0-4: no disability. 5-14: mild disability. 15-24: moderate disability. 25-34: sever disability. 35-50: completely disabled.

The painDETECT questionnaire was specifically developed to detect neuropathic pain components in adult patients with low back pain. PainDETECT is a scale of 0 to 35, with 0 being no disability to 35 being max disability.

The painDETECT questionnaire was specifically developed to detect neuropathic pain components in adult patients with low back pain. PainDETECT is a scale 0 to 38, with 0 being no disability to 38 being max disability.

Patient Global Impression of Change (PGIC) scale is a seven-point single-item scale ranging from 7 'very much worse' to 1 'very much improved'.

TSQ is a questionnaire to rate level of satisfaction or dissatisfaction with the Intrathecal Drug Delivery- patients were asked preference for either intrathecal solution. Patient preferences for each solution were measured. This data represents the total number of patient's that received a trial and the total number of patients who preferred each solution. Higher values indicate a greater number of study participants preferred a specific arm. Patients with no preference are listed separately.

AE is any untoward medical occurrence in the patient which does not necessarily have a causal relationship with this infusion treatment

Number of participants that had increases or decreases in the dose or frequency of pain medication

University Hospitals Cleveland Medical Center

Professor, Department of Anesthesiology/Chief, Division of Pain Medicine

Deaths and Adverse Events were not collected per intervention. All participants participated in all interventions. All participants were combined into one group for the adverse event tracking.

All Study Participants

All participants participated in all interventions so for the baseline characteristics all participants were combined into one arm/group.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Dr. Salim Hayek

Baseline

End of intrathecal infusion of solution (Day 2)

End of intrathecal infusion of solution (Day 3)

Continuous intrathecal prognostic infusion test of active solution: intrathecal bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml

6 hour washout followed by

Continuous intrathecal prognostic infusion test of inactive placebo solution: preservative-free normal saline

Continuous intrathecal prognostic infusion test: The patient is infused with solution through the percutaneous intrathecal catheter at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours

Bupivacaine: Bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml continuous infusion at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours

Fentanyl: Bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml continuous infusion at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours

Placebo: Intrathecal infusion of normal saline at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours

Intrathecal Drug Delivery System (IDDS): 40-mL IDDS containing a solution of fentanyl 50 mcg/mL with bupivacaine 30 mg/mL

Active Solution Followed by Inactive Placebo Solution

First Intervention: Continuous infusion of placebo solution: normal saline at a rate of 0.5-1.0mL/hr for another 14-18 hour.

Washout: 4-6 hr washout infusion of preservative-free saline0.2 mL/hr. Second Intervention: Continuous infusion of active solution: intrathecal bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml at a rate of 0.5-1.0 mL/hr for 14-18 hours.

Inactive Placebo Solution Followed by Active Solution

Change in Numerical Rating Scale Pain Scores (NRS) With Activity

Change in Numerical Rating Scale Pain Scores (NRS) at Rest

Continuous intrathecal prognostic infusion test of inactive placebo solution: preservative-free normal saline

6 hour washout followed by

Continuous intrathecal prognostic infusion test of active solution: intrathecal bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml

Continuous intrathecal prognostic infusion test: The patient is infused with solution through the percutaneous intrathecal catheter at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours

Bupivacaine: Bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml continuous infusion at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours

Fentanyl: Bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml continuous infusion at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours

Placebo: Intrathecal infusion of normal saline at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours

Intrathecal Drug Delivery System (IDDS): 40-mL IDDS containing a solution of fentanyl 50 mcg/mL with bupivacaine 30 mg/mL

Change in Oswestry Disability Score (ODI)

Change in painDETECT Total

Change in painDETECT Final

Change in Patient Global Impression of Change (PGIC)

Intrathecal Infusion 1- Sequence 1

Intrathecal Infusion 2- Sequence 1

No preference- Sequence1

Intrathecal Infusion 1- Sequence 2

Intrathecal Infusion 2- Sequence 2

No preference- Sequence 2

Intrathecal infusion 1 is the first infusion subjects received in the study. It corresponds to the active agents in Sequence 1 and saline in sequence 2.

Intrathecal infusion 2 is the second infusion subjects received in the study. It corresponds to saline in Sequence 1 and to the active agents in sequence 2.

All participants were analyzed together for this outcome.

Treatment Satisfaction Questionnaire (TSQ)

Deaths and Adverse Events were not collected per intervention

Adverse Event (AE)

Continuous intrathecal prognostic infusion test of active solution: intrathecal bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml 6 hour washout followed by Continuous intrathecal prognostic infusion test of inactive placebo solution: preservative-free normal saline Continuous intrathecal prognostic infusion test: The patient is infused with solution through the percutaneous intrathecal catheter at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours Bupivacaine: Bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml continuous infusion at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours Fentanyl: Bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml continuous infusion at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours Placebo: Intrathecal infusion of normal saline at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours Intrathecal Drug Delivery System (IDDS): 40-mL IDDS containing a solution of fentanyl 50 mcg/mL with bupivacaine 30 mg/mL

Active Solution Followed by Inactive Place Solution

Continuous intrathecal prognostic infusion test of inactive placebo solution: preservative-free normal saline 6 hour washout followed by Continuous intrathecal prognostic infusion test of active solution: intrathecal bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml Continuous intrathecal prognostic infusion test: The patient is infused with solution through the percutaneous intrathecal catheter at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours Bupivacaine: Bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml continuous infusion at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours Fentanyl: Bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml continuous infusion at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours Placebo: Intrathecal infusion of normal saline at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours Intrathecal Drug Delivery System (IDDS): 40-mL IDDS containing a solution of fentanyl 50 mcg/mL with bupivacaine 30 mg/mL

Change in Medication

Overall Study

Behaviors and Mental Disorders

Quality of Life

Radiotherapy dose: 20 Gy/5 fractions/1 week or 8 Gy/1 fraction (at the discretion of the Radiation Oncologist)

Vertebroplasty followed by radiotherapy within 2-3 weeks

Radiotherapy dose: 20 Gy/5 fractions/1 week or 8 Gy/1 fraction (at the discretion of the Radiation Oncologist)

External beam radiation therapy is a type of radiation therapy used for cancer treatment. A machine is used to aim high-energy rays from outside the body into tumor

Radiotherapy

Vertebroplasty is a procedure for stabilizing compression fractures in the spine. Bone cement is injected into vertebrae that have cracked or broken. The cement hardens, stabilizing the fractures and supporting your spine.

Vertebropladty

Since patients with spinal metastases are living longer, durable palliation with long-term tumor control are becoming increasingly important.

EBRT results in durable local control of bone metastasis. However, about 25 % of patients with spinal metastases only achieved complete pain relief following EBRT for a median duration of less than 4 months. This could be partly due to spinal instability. In addition, almost half of the patients who receive EBRT will subsequently develop VCFs . Hence, RT does not stabilize the spine secondary to VCFs and is not effective in preventing imminent VCFs. Vertebroplasty has rapidly reduced pain and improved function in patients with VCFs. However, vertebroplasty does not provide local tumor control similar to EBRT.

It is theorized that combining vertebroplasty with EBRT will stabilize the spine, relieve the pain, prevent imminent VCFs and minimize or avoid the need for opioids. It is hypothesized that combining a spine stabilization procedure such as vertebroplasty with RT will be the most effective management for patients with spinal metastases than RT alone for patients with spinal metastases. Combined vertebroplasty and radiotherapy is not a standard treatment option at present. This study is designed to quantify the advantage of adding vertebroplasty to radiotherapy for patients with spinal metastases. If the study is proven to be significant, it could become the standard of care for patients with spinal metastases.

Trial of Combined Radiotherapy and Vertebroplasty for Patients With Painful Metastatic Spinal Lesions

A Phase II Randomized Trial of Combined Radiotherapy and Vertebroplasty to Improve the Quality of Life of Patients With Painful Metastatic Localized Spinal Lesions

The primary end point is the improvement in pain score of at least 2 points (a decrease of 2 points) on the visual analogue Scale (VAS) without concurrent increase in opioids.

The primary end point is the improvement in pain score of at least 2 points (a decrease of 2 points) on the Brief Pain Inventory (BPI) without concurrent increase in opioids.

The improvement in back-specific physical functioning is evaluated by the change in Roland-Morris disability questionnaire (RDQ) score.

The incidence of vertebral compression fractures will be evaluated by standing lateral spine radiographs of the thoracic and lumbar vertebrae.

Pain response will be assessed by VAS and evaluated using a patient diary based on the International Bone Metastases Working Party Criteria. Based on intake of analgesics, the daily oral morphine equivalent dose (OMED) will be calculated.

Pain response will be assessed by BPI and evaluated using a patient diary based on the International Bone Metastases Working Party Criteria. Based on intake of analgesics, the daily oral morphine equivalent dose (OMED) will be calculated.

Cross Cancer Institute

AHS Cancer Control Alberta

Nutritional and Metabolic Diseases

Osteoporosis

Bone Neoplasms

Bone Diseases

Bone Diseases, Metabolic

Metabolic Diseases

Acute Graft Versus Host Disease

Balloon Kyphoplasty

Prof. Johnell, MD

The primary objective of this study is to compare the effectiveness of standard medical therapy alone to kyphoplasty using the KyphX system for the treatment of acute vertebral body compression fractures.

FREE Study - Fracture Reduction Evaluation

An International Multicentric, Multidisciplinary Prospective and Randomized Study to Compare Minimally Invasive Reduction and Fixation Using the KyphX System and Radiopaque PMMA Cement to Medical Therapy Alone for the Treatment of Painful, Acute Osteopenic Vertebral Body Compression Fractures

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Treatment of Malignant Vertebral Fractures With Percutaneous Balloon Kyphoplasty.	NCT00748631	Vertebral Fract... Multiple Myelom... Osteolytic Meta...	balloon kyphopl...	18 Years -	Assistance Publique - Hôpitaux de Paris
To Compare Conservative Management Vs. Balloon Kyphoplasty in the Treatment of VCFs in Patients With Multiple Myeloma	NCT02732925	Multiple Myelom...	Arm 2 Balloon K... Conservative Ma...	18 Years - 80 Years	Royal National Orthopaedic Hospital NHS Trust
Determining the Prognostic Value of Continuous Intrathecal Infusion	NCT03523000	Lumbar Post-Lam... Chronic Low Bac... Vertebral Compr... Failed Back Sur...	Continuous intr... Bupivacaine Fentanyl Placebo Intrathecal Dru...	30 Years -	University Hospitals Cleveland Medical Center
To Compare Conservative Management Vs. Balloon Kyphoplasty in the Treatment of VCFs in Patients With Multiple Myeloma	NCT02732925	Multiple Myelom...	Arm 2 Balloon K... Conservative Ma...	18 Years - 80 Years	Royal National Orthopaedic Hospital NHS Trust
Trial of Combined Radiotherapy and Vertebroplasty for Patients With Painful Metastatic Spinal Lesions	NCT04242589	Spinal Metastas...	Radiotherapy Vertebropladty	18 Years -	AHS Cancer Control Alberta
FREE Study - Fracture Reduction Evaluation	NCT00211211	Osteopenia Osteoporosis Multiple Myelom... Bone Neoplasms	Balloon Kyphopl...	21 Years -	Medtronic Spinal and Biologics
To Compare Conservative Management Vs. Balloon Kyphoplasty in the Treatment of VCFs in Patients With Multiple Myeloma	NCT02732925	Multiple Myelom...	Arm 2 Balloon K... Conservative Ma...	18 Years - 80 Years	Royal National Orthopaedic Hospital NHS Trust
Trial of Combined Radiotherapy and Vertebroplasty for Patients With Painful Metastatic Spinal Lesions	NCT04242589	Spinal Metastas...	Radiotherapy Vertebropladty	18 Years -	AHS Cancer Control Alberta

Spots Global Cancer Trial Database for vertebral compression fracture