Infections

All Conditions

Symptoms and General Pathology

Wounds and Injuries

Blood and Lymph Conditions

Rare Diseases

Communicable Diseases

Emergencies

Hyperthermia

Neutropenia

Fever

Sepsis

Toxemia

Febrile Neutropenia

Body Temperature Changes

Agranulocytosis

Leukopenia

Cytopenia

Hematologic Diseases

Leukocyte Disorders

Granulocytopenia

Anti-Infective Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Antineoplastic Agents

Anti-Bacterial Agents

Amoxicillin

Meropenem

Clavulanic Acid

Amoxicillin-Potassium Clavulanate Combination

Levofloxacin

Ofloxacin

Penicillins

Lactams

beta-Lactams

Antibiotics, Antitubercular

Clavulanic Acids

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

beta-Lactamase Inhibitors

Patient's blood sample will be expedited for complete blood count with differentials. Intravenous antibiotic is given depending on absolute neutrophil count. If neutropenia is present, broad-spectrum antibiotic (meropenem 1 g or levofloxacin 500 mg) will be given after septic workup within 1 hour of registration in emergency department before transfer to wards. If absent, antibiotic according to "Hospital Authority Interhospital Multi-disciplinary Programme on Antimicrobial ChemoTherapy (IMPACT)" with reference to previous bacterial sensitivity pattern, or amoxiclav 1.2 g if not specified, will be given. Other interventions are given according to clinical needs. The regimen is continued until clinicians recommend an alternative antimicrobial based on clinical grounds, or detection of other pathogens which indicate another antimicrobial.

The control group refers to the existing clinical pathway which guides management of adult patients with suspected NF in ED. Without information of absolute neutrophil count, Meropenem 1 g IV bolus (or Levofloxacin 500 mg IV infusion over 1 hour if Penicillin-allergic) will be given within 1 hour of ED registration after septic workup. Other interventions are given according to clinical needs.

Subsequent treatment in wards will be determined by doctor's clinical judgement, on a personalised basis. Each patient will be assessed by a parent team member. There is no standardised antibiotic de-escalation protocol in place, but it is a usual practice to continue Meropenem or Levofloxacin injections until clinical improvement, rising ANC, and negative culture results. After that it will be replaced with an antibiotic with a narrower spectrum, such as oral Amoxiclav, before discharge.

Given if patient has no known allergies at 1 g IV bolus within 1 hour of ED registration, then every 8 hours

Meropenem Injection

Given if patient is allergic to beta lactam at 500 g IV in 100 mL 0.9% sodium chloride solution, infused over 1 hour started within 1 hour of ED registration, then every 24 hours. If the patient can tolerate oral drugs, 500 mg daily after the first IV dose.

Given if patient has no known allergies at 1.2 g IV bolus within 1 hour of ED registration, then every 8 hours. If the patient can tolerate oral drugs, 1 g twice daily after the first IV bolus.

Amoxicillin Clavulanate

Any antibiotic for empirical therapy of common infections as recommended by the fifth version of "Hospital Authority Interhospital Multi-disciplinary Programme on Antimicrobial ChemoTherapy (IMPACT)" guideline, with reference to previous bacterial sensitivity pattern

Antibiotic

Timothy Hudson Rainer, MBBCh; MRCP

Timothy Hudson Rainer, MBBCh, MRCP

This is a comparative study for adult participants with cancer who are suspected to have neutropenic fever (or fever with low neutrophil count) in emergency department. Neutrophil is a kind of defensive white blood cell combating against infection, especially by bacteria and fungi. Low neutrophil can be part of the disease progress or secondary to some cancer treatment. These participants are at high risk of developing infection-related complications including death.

Currently a dedicated clinical pathway has been in place in emergency department for suspected neutropenic fever, which offers fast-track medical consultation, blood tests and a very strong antibiotic (meropenem) as the first choice within 1 hour of registration. However, majority of such participants' neutrophil counts are not low. Most of them have no bacterial infection in the body, and have unremarkable short hospital stays. Early administration of meropenem in the majority of cases may be unnecessary and imposes risk of developing antibiotic resistance.

This study attempts to answer the question, "In adult participants with cancer presenting to emergency department with suspected neutropenic fever, when compared with conventional treatment, can a new protocol guided by fast-track neutrophil count reduces prescription of meropenem?" Agreed participants will be randomly assigned to the conventional treatment group, or the new treatment group. For those who are assigned to the new treatment group, blood will be taken and sent to the hospital laboratory for urgent analysis of neutrophil count. Participants with proven low neutrophil counts will still receive meropenem, while those without low neutrophil counts will receive less strong antibiotic according to their clinical diagnoses, such as Augmentin. They will be followed up on the first 7 days, and then on the 14th, 30th, 90th, and 180th days after recruitment. Comparisons will be made to see how much less meropenem will be prescribed, and whether more serious adverse events will happen. The study is expected to take 37 months to complete. Duration of data collection, including the day of last follow up, is estimated to be 33 months.

1. Background

1.a. Burden of neutropenic fever Neutropenic fever (NF), or febrile neutropenia, is characterised by high body temperature and low absolute neutrophil count (ANC) following myelosuppressive cancer treatment.\[1\] It occurs in 5 - 10 percent of patients with early-stage solid tumours, 20 - 25 percent with non-leukaemic haematological cancers, 85 - 95 percent with acute leukaemia,\[2\] and 13 - 21 percent with metastatic solid tumours.\[1\] It is more common after the first cycle of chemotherapy. 7.83 per 1,000 cancer patients were hospitalised for NF annually in the United States (US).\[3\] With earlier cancer recognition, and more prescriptions of chemotherapeutic agents and targeted therapies, the figures are expected to rise.

NF is associated with unplanned chemotherapy interruptions and relative dose intensity (RDI) reductions more than 15 percent, which undermine treatment success rates and overall survival.\[2\] When complicated by neutropenic sepsis, a dysregulated host response against infection, NF becomes an oncological emergency. The mortality rate is 3 - 18 percent following complications e.g. hypotension, respiratory failure, encephalopathy, cardiac failure and arrhythmia, renal failure, haemorrhage, and admission to intensive care unit (ICU).\[4\] Risk factors of life-threatening infections are severe neutropenia, protracted neutropenia, and splenectomy.\[5\] Mortality risk increases with advanced age, comorbidities, clinically documented infection, bacteraemia, leukaemia and lung cancer as underlying malignancies.\[4,6\]

The cost of managing NF remains substantial for healthcare systems worldwide. The mean direct hospitalisation costs in the US, Germany, and Singapore were US$19,110 (1995-2000), €3,950 (2005-2006), and US$4,913 (2009-2012) respectively.\[6-8\] Higher costs are associated with inpatient treatment, comorbidities, discharge, deaths, male sex, and infection.\[9\]

1.b. Diagnostic criteria NF is defined by 1) single oral temperature ≥ 38.3 degree Celsius (101ºF), or ≥ 38.0 degree Celsius (100.4ºF) sustained over 1 hour; and 2) ANC \< 1.0 x 109/L ("moderate" neutropenia). Neutropenia becomes "severe", "profound" and "protracted" if ANC \< 0.5 x 109/L, \< 0.1 x 109/L, and lasts for more than one week, respectively.\[10\] This definition applies to oncological and haematological participants only.

1. c. Aetiology Neutrophils are recruited early during the acute phase of bacterial and fungal infections.\[11\] Fever may be the only manifestation of infection during neutropenia because the typical signs of inflammation are obscured. Neutropenia is usually acquired by myelosuppressive cancer treatments, and pre-engraftment phases of haematopoietic stem cell transplantation (HSCT). Bone marrow failure and defective neutrophil maturation are other possible mechanisms.\[12\]

   NF can have infectious and non-infectious causes. Fever of unknown origin, chemotherapy-related oral mucositis, tumour-related cytokine release, transfusion-related reaction, drug reaction, graft-versus-host disease, and thromboembolism are common non-infective causes.\[13\] 30 - 50 percent are infections by clinical presentation or microbiology,\[14\] whilst only 20 - 30 percent are microbiologically documented infections.\[15\] Bloodstream infections, bacterial translocation from respiratory tract and perianal region, and central venous catheter are major sources.

1.d. Situation in Hong Kong Local public emergency departments (EDs) have implemented clinical pathways for suspected NF, which expedite medical consultation, septic workup, and broad-spectrum antibiotics such as Meropenem or Piperacillin/Tazobactam. The target time from ED registration to antibiotic administration, or Door-To-Antibiotic (DTA) time, is within 1 hour disregarding ANC, in line with international guidelines.\[16-18\] DTA times are shortened after implementing clinical pathways in local ED.\[19\] Local epidemiology, antibiotic sensitivity patterns, and healthcare cost in managing NF are understudied. It has been shown that inadequate antibiotic regimen was more significantly associated with ICU admissions and mortality than longer DTA times. Presence of sepsis or septic shock, prior colonisation with drug resistant strains, and risk stratifying indices, are criteria to judge antibiotic adequacy.\[20\]

1. e. Antibiotic stewardship for cancer participants Participants with cancer are frequently exposed to antibiotics for treatment and prophylaxis, therefore they are more vulnerable to multi-drug resistance, and are in special need for antibiotic stewardship.\[21\] Broad-spectrum antibiotics are often started empirically in ED for suspected NF, assuming infection by drug-resistant bacteria. However, clinicians may not proactively de-escalate subsequent antibiotics. Prolonged exposures to parenteral broad-spectrum antibiotic impose risks of nosocomial infection and injection site complications.

   Gram-negative bacilli are more frequent in neutropenia. Staphylococcus aureus, Acinetobacter and Enterobacter species are more frequent in non-neutropenic bloodstream infections.\[22\] More drug resistant (MDR) strains, such as Extended-spectrum Beta-lactamase (ESBL)-producing Enterobacteriaceae, MDR Pseudomonas aeruginosa, and MDR Acinetobacter were isolated from neutropenic patients in a survey in China.\[23\]
2. Research (PICO) question In adult participants with cancer presenting to the ED with suspected NF, can an ED protocol guided by Fast-tRack Absolute Neutrophil Count (FRANC protocol) compared with conventional care guided by clinical suspicion alone improve safe antibiotic stewardship?
3. Objective and purpose

3.a. Objectives

In adult participants presenting to the ED with suspected NF:

* To investigate the effectiveness of the FRANC protocol to improve antibiotic stewardship by restricting meropenem use except for confirmed neutropenic or clinically unstable participants; and
* To investigate the safety of the FRANC protocol. 3.b. Primary hypothesis In participants presenting to ED with suspected NF, the FRANC protocol significantly reduces unnecessary use of Meropenem compared with normal Standard of Care (SoC).

  3.c. Secondary hypothesis In participants presenting to ED with suspected NF, there is no significant difference between those receiving the FRANC protocol and those receiving SoC for serious adverse events including death.

  4. Methods

  4.a. Participants 4.a.1. Target population This trial targets to adult participants attending ED because of fever, who are at risk of neutropenia related to cancer therapies and underlying conditions.

  4.a.2. Study location The trial will be conducted in the ED of Queen Mary Hospital with an average annual attendance of 125,000. The hospital is a tertiary referral centre for HSCT and oncological services which received more than 500 adults with suspected NF via the ED in 2019.

  4.a.3. Recruitment and screening Alert cards are routinely issued to participants at risk of neutropenia during follow-ups in Clinical Oncology and Haematology centres. They are reminded to visit EDs as soon as possible when fever occurs. A neutropenic risk alert is set to pop up in the Clinical Management System (CMS) that is shared among all public medical facilities. It is valid for 6 weeks from the last chemotherapy against solid tumours, or lifelong for haematological malignancies, and HSCT.

When febrile participants with valid alerts attend, the triage nurse will declare "1 - Critical" or "2 - Emergency" categories according to clinical state. Consultations by emergency physician will start within 15 minutes. Participants who receive cancer treatment in other medical facilities will also be included if they meet the same criteria.

Participants will then be screened for eligibility by trained research staff for inclusion and exclusion criteria in the ED. Potential participants will be invited to provide informed consent in written, signed, and dated forms. They can decline at any time.

4.a.4. Sample size For antibiotic stewardship A sample size of 344 participants (172 per group) will achieve 80 percent power to detect a superiority difference between two group rates of meropenem prescription. We set the superiority margin at 10 percent and assume that the control group has Meropenem usage rate of 91.8 percent (based on preliminary data) and 71.8 percent for intervention group. The calculation is based on a one-sided Z test at the significance level of 0.05.

4.a.5. Randomisation \& allocation concealment We aim to achieve balanced treatment assignments in 1:1 ratio with simple randomisation by a computer-generated code list. The code is not broken until the last participant is enrolled and has completed 180 days of follow-up. It will be implemented using independent electronic case data files to ensure allocation concealment.

4.b. Data processing and analysis 4.b.1. Data processing All data will be entered electronically by research staff to password-protected, secured, web-based system with tailor-made recording forms using tablet computers. 5 percent of all data will be checked for accuracy. All hard copies will be restricted and locked in unit cabinets. All prevailing regulations by The University of Hong Kong and the Hospital Authority will be strictly followed. An audit trail will be made to include the number of participants screened, approached, recruited, and excluded (with reasons). Participant and clinical staff responses, and data completeness will be evaluated.

4.b.2. Data analysis 4.b.2.a. Primary analysis Baseline characteristics between two groups will be assessed for potential imbalances, which will be adjusted for when comparing outcomes. Intention-to-treat (ITT) analysis will be used by imputing all non-responses at follow-up with baseline values, which yields more conservative estimates of effect sizes. The missing data for the primary outcome is expected to be \< 1 percent because most data is retrievable from electronic participant records with electronic time stamps. Statistical analysis will be done using Statistical Package of Social Sciences (SPSS) version 26 (IBM SPSS Statistics, New York, US) with biostatistician support.

Main effect: Intervention vs. Control on proportion of participants receiving Meropenem in 7 days using Chi-squared test.

4.b.2.b. Secondary analyses

* All secondary outcomes at different time points using generalised mixed effect model for multiple intra-participant and inter-participant observations. Main and interaction effects will be assessed.
* Subgroup analysis to primary outcome based on age, gender, type of cancer/ conditions, disease status, therapy received, time interval from last chemotherapy or HSCT to ED registration, at 30, 60, 90 days (4) Sensitivity of ITT and per-protocol analyses for pre-defined co-variates, missing data (including participants lost to follow-up), will be done. Imputation method will depend on actual pattern of missing data.
* If the attrition rate is more than 5 percent, risks of attribution bias and influence to statistical power will be assessed.
* Complication rates over time will be compared with Poisson mixed effects models. Uses of inotrope, mechanical ventilation, renal replacement therapy, and ICU are analysed against mortality using appropriate survival analyses with time to event data.

This is a single-center, pragmatic, open-labelled, randomized, controlled trial with 1:1 parallel-group assignment, which aims to establish superiority in antibiotic stewardship.

Fast-track Blood Test for Suspected Fever by Deficiency of a Kind of White Blood Cells As Main Defense Against Infection

Fast-track Absolute Neutrophil Count in Suspected Neutropenic Fever (The FRANCiS-NF Trial): A Single-centre, Pragmatic, Open-label, Randomised, Controlled Trial

Proportion of participants in each group receiving Meropenem

Rate and type of documented infective focus

* Days to defervescence (body temperature less than 38 degree Celsius)
* Days to resolution of symptoms and signs of infection

* Hypotension (systolic blood pressure \< 90 mmHg)
* Respiratory failure (partial pressure of oxygen in arterial blood \< 60 mmHg, or 8 kilopascal, adjusted for hyperventilation)
* Altered mental state (Glasgow Coma Scale \< 15)
* Congestive heart failure documented radiologically
* Acute kidney injury (serum creatinine \> 2x baseline, or estimated glomerular filtration rate (eGFR) \> 50 percent increase from baseline, or urine output \< 0.5 mL/kg/h x 12 h)
* Acute liver failure (International Normalised Ratio (INR) \> 1.5 in non-warfarin user, hepatic encephalopathy, total bilirubin \> 85.5 µmol/L or 5 mg/dL)
* Rate of therapeutic failure (recurrence of fever after defervescence)

* Rate of inotrope/ vasopressor use
* Rate of assisted / mechanical ventilation
* Rate of renal replacement therapy
* Rate of 3 or more units of blood transfusion for haemorrhage
* Rate of additional antimicrobial treatment
* Rate of Intensive Care Unit (ICU) admission

Total in-hospital days from the time of index ED admission

Changes in chemotherapy schedule following index admission (postponement, dose reductions, participant defaults)

Rates of any readmission except for planned chemotherapy

Time from the day of randomisation to the date of death, all-cause or infection-related

Type and route of antibiotics administered, from the time of randomisation to hospital discharge, or from the time of randomisation to the expected date of completion of prescribed antibiotic courses after discharge, whichever the later

Mean total dose of antibiotics used, in milligrams, from the time of randomisation to hospital discharge, or from the time of randomisation to the expected date of completion of prescribed antibiotic courses after discharge, whichever the later

Total days of therapy (DOT) per admission - the unit measure is defined as one day in which a patient is given a drug, regardless of dose per admission.

Defined daily dose (DDD) per admission is the assumed average maintenance dose, in milligrams, per day for a drug used for its main indication.

Development of resistance, defined as clinical isolates resistant to antibiotics previously used in the febrile episode. Surveillance sampling will not be conducted.

Physical, social, emotional and function well being of participants will be evaluated using the standardised 27-item questionnaire, "Functional Assessment of Cancer Therapy - General" (FACT-G).

Physical, social, emotional and function well being of participants will be evaluated using the Functional Assessment of Cancer Therapy - Neutropenia (FACT-N). It is a modified version of the Functional Assessment of Cancer Therapy - General (FACT-G) with the Neutropenia subscale, which is targeted for adult cancer patients with neutropenia.

Financial toxicity is evaluated using the Functional Assessment of Chronic Illness Therapy - COprehensive Score for financial Toxicity (FACIT-COST). The COST is a patient-reported outcome measure that describes the financial distress experienced by cancer patients. The FACIT System screens for financial toxicity and to provide a global summary item for financial toxicity.

Queen Mary Hospital, Hong Kong

The University of Hong Kong

Nervous System Diseases

Behaviors and Mental Disorders

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Heart and Blood Diseases

Immune System Diseases

Digestive System Diseases

Nutritional and Metabolic Diseases

Neoplasms

Skin and Connective Tissue Diseases

Dementia

Kidney Diseases

Critical Illness

Lung Diseases, Obstructive

Pulmonary Disease, Chronic Obstructive

Parkinson Disease

Heart Failure

Sclerosis

Multiple Sclerosis

Heart Arrest

Hepatic Encephalopathy

Multiple Organ Failure

Lung Diseases

Brain Diseases

Renal Insufficiency, Chronic

Renal Insufficiency

Parkinsonian Disorders

Ganglion Cysts

Synovial Cyst

Basal Ganglia Diseases

Central Nervous System Diseases

Movement Disorders

Synucleinopathies

Neurodegenerative Diseases

Autoimmune Diseases

Demyelinating Autoimmune Diseases, CNS

Autoimmune Diseases of the Nervous System

Demyelinating Diseases

Urologic Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Chronic Disease

Disease Attributes

Heart Diseases

Liver Failure

Hepatic Insufficiency

Liver Diseases

Gastrointestinal Diseases

Brain Diseases, Metabolic

Metabolic Diseases

Respiratory Tract Diseases

Shock

Chronic Graft Versus Host Disease

Acute Graft Versus Host Disease

The interventional group (Ig) will have an early palliative care consultation ordered during their stay in the emergency department.

The control group will be treated as standard of care. Palliative care consultations may or may not be ordered at the attending physician's discretion.

Early order of palliative care consultation

Robert Zalenski, M.D., M.A.

A prospective randomized controlled trial studying the ordering of palliative care consultations in the emergency department (Ig) versus later palliative care consultations in the hospital--ICU or hospital ward(Cg). Patients will be randomly allocated to Ig or Cg with a 1:1 ratio.

Timing of Acute Palliative Care Consultation in Critically Ill Patients

A Randomized Allocation of Palliative Care Consultation in the Emergency Department Compared to Usual Practice

The proportion of patients who received an ACP CMS billing codes (which took effect in January 2016), in Ig vs. Cg will be evaluated using one or both of the new CPT codes for Advance care planning (ACP) services...including the explanation and discussion of advance directives such as standard forms (with the completion of such forms, when performed) by the physician or other qualified health profession; first 30 (15-45)minutes, face to face with the patients, family member(s) and/or surrogate Code 99497; and each additional 30 (46-75 minutes)-Code 99498 (Federal Register, 2015).

The investigators will align treatment preferences with medical orders, replicated as reported in the study by Mack et al. Proportions of patients coded as having a match will be compared across the treatment and control groups. For everyone who gets ACP during the study, patients or their surrogates will be asked by a member of the care team-either palliative care if they are consulted, or the hospital based care team if they are not: "If you could choose, would you prefer (a) treatment that focuses on attempting to extend your time as much as possible, even if doing so means more pain and discomfort, or (b) a plan of care that focuses on relieving pain and discomfort and improving quality of life, even though that may mean not living as long.

This outcome will be measured on a continuous scale. The net-promoter score will be measured at baseline (at randomization) and at hospital discharge for a change in value. It is measured on a scale of 1-10. Whoever signs the consent (patient of LAR) will be asked the net promoter score, and that will be reassessed by them at discharge, unless the patient has died-and the variable will then be recorded as missing. The PSQ will be administered by research assistants at the time of the patient's discharge. If the patient is incapacitated, then it will be asked of the patient's closest family caregiver. So PSQ is only at discharge of patient or available, most involved, family caregiver.

Blue Cross Blue Shield of Michigan Foundation

Wayne State University

Principle Investigator

Cancer Pain

Pain

Breakthrough Pain

Adjuvants, Anesthesia

Analgesics

Central Nervous System Depressants

Fentanyl

Hydromorphone

Analgesics, Opioid

Narcotics

Anesthetics

Anesthetics, Intravenous

Anesthetics, General

Fentanyl 100 mcg nasal spray administered plus hydromorphone PCA. All study patients receive demand dosing patient-controlled analgesia (PCA) with intravenous hydromorphone. Initial loading dose 0.2 mg with demand doses of 0.2 mg and lockout interval of 15 minutes. There will be no basal dose and the 8-hour dose limit will be 6.4 mg.

Placebo nasal spray administered plus hydromorphone PCA . All study patients receive demand dosing patient-controlled analgesia (PCA) with intravenous hydromorphone. Initial loading dose 0.2 mg with demand doses of 0.2 mg and lockout interval of 15 minutes. There will be no basal dose and the 8-hour dose limit will be 6.4 mg.

100 mcg nasal spray administered in each nostril.

Fentanyl Nasal Spray

Initial loading dose 0.2 mg with demand doses of 0.2 mg and lockout interval of 15 minutes. There will be no basal dose and the 8-hour dose limit will be 6.4 mg.

Hydromorphone PCA

1 placebo nasal spray administered in each nostril.

Placebo Nasal Spray

Knox H. Todd, MD

The goal of this clinical research study is to learn if fentanyl nasal spray can help decrease pain related to cancer when used with other drugs for pain. Researchers also want to know if this drug can help decrease the length of your stay in the Emergency Department.

In this study, fentanyl nasal spray will be compared to a placebo nasal spray. A placebo is not a drug. It looks like the study drug but it is not designed to treat any disease or illness. It is designed in this study to be compared with the study spray to learn if the study spray has any real effect.

You will also be given intravenous (IV) pain drugs. You will be given these drugs even if you decide not to take part in this study.

Study Groups:

If you agree to take part in this study, you will be randomly assigned (as in the flip of a coin) to receive either fentanyl nasal spray or a placebo nasal spray. You will have an equal chance of being assigned to either group.

Neither you nor the study staff will know if you are receiving the study spray or the placebo. However, if needed for your safety, the study staff will be able to find out what you are receiving.

Study Visit and Study Treatment:

During your stay in the Emergency Department today, the following tests and procedures will be performed:

* Your vital signs (blood pressure, heart rate, temperature, and breathing rate) will be recorded.
* Information from your medical record about your age, sex, race, status of the disease, and any drugs that you may be taking for pain.
* The study nurse will also ask you some questions about your pain. It should take about 5 minutes to answer these questions.

You will then begin study treatment with either the fentanyl nasal spray or placebo nasal spray. The study nurse will help you use the nasal spray.

You will stay in the Emergency Department and will be monitored for up to 8 hours after the treatment has been administered. During this time, you will be asked about your pain and any side effects you may be having. The study nurse will also monitor your IV pain drug levels and other vital signs.

Length of Treatment:

Your active participation in this study will be over after your are monitored for up to 8 hours, at which time you will either be discharged to go home or admitted to the hospital based on your pain response and any other health problems that may be found during your visit to the Emergency Department.

Follow-Up Phone Call:

About 24 hours after your participation is over, the study nurse will call you by phone to ask if you experienced any other side effects since finishing the study treatment. The phone call should only last about 5 minutes. If you are still an inpatient at the hospital, the study nurse may visit you and ask you these questions in person.

This is an investigational study. Fentanyl nasal spray is FDA approved and commercially available for the treatment of pain. It's use to help with cancer pain in the Emergency Department is investigational.

Up to 60 patients will take part in this study. All will be enrolled at MD Anderson.

Fentanyl for Breakthrough Pain in the Emergency Department

A Randomized Controlled Double-Blind Trial of Fentanyl Nasal Spray (Lazanda) Plus Hydromorphone Demand PCA Versus Placebo Nasal Spray Plus Hydromorphone Demand PCA for Treatment of Breakthrough Cancer Pain in the Emergency Department

Primary outcome is total pain relief score (TOTPAR4) at 4 hours after treatment initiation. TOTPAR4 defined as the sum of hourly pain relief scores after baseline to four hours after the first administered dose of Lazanda or placebo. Scores range from -1 (worse pain) to 4 (complete relief). Range of possible TOTPAR4 summed scores is -4 to 16. A TOTPAR4 score greater than or equal to 8 is considered a positive response.

Archimedes Pharma US, Inc.

M.D. Anderson Cancer Center

Placebo nasal spray administered in each nostril plus hydromorphone PCA. Initial PCA loading dose 0.2 mg with demand doses of 0.2 mg and lockout interval of 15 minutes. There was no basal dose and the 8-hour dose limit was 6.4 mg.

Placebo

Fentanyl 100 mcg nasal spray administered in each nostril plus hydromorphone PCA. Initial PCA loading dose 0.2 mg with demand doses of 0.2 mg and lockout interval of 15 minutes. There was no basal dose and the 8-hour dose limit was 6.4 mg.

Intervention

Patient consented but admitted to hospital before medication administered.

No Medication

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Pain Score between 7 and 10 using an 11-point National Rating Scale (NRS).The 11-point numeric scale ranges from '0' representing one pain extreme (e.g. "no pain") to '10' representing the other pain extreme (e.g. "pain as bad as you can imagine" or "worst pain imaginable")

Number of Participants with Pain Score between 7 and 10 using an 11- point (NRS)

Kumar Alagappan,Chair, Emergency Medicine

One participant consented but admitted to hospital before medication administered

Number of Participants With Total Pain Relief Score (TOTPAR4) at Four Hours After Treatment Initiation.

Placebo nasal spray administered in each nostril plus hydromorphone (PCA) Initial Patient Controlled Analgesia. (PCA) loading dose 0.2 mg with demand doses of 0.2 mg and lockout interval of 15 minutes. There was no basal dose and the 8-hour dose limit was 6.4 mg.

Overall Study

Neurologic Manifestations

Experimental group would receive acupuncture at specific acupoints for 15 minutes.

Control group would receive another intervention that we would put Vaccaria seeds near the acupoints but without acupressure for the same period.

Acupuncture in the Hegu (LI4), Shousanli (LI10), Zusanli (ST36), Yanlinquan (GB34), Taichong (LV3) and Ouch point. Needles would be correctly inserted and manually stimulated until the 'De Qi' sensation is elicited. The needles would stay in place for 15 minutes.

acupuncture

We put Vaccaria seeds near the acupoints without acupressure as an intervention in control group.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Fast-track Blood Test for Suspected Fever by Deficiency of a Kind of White Blood Cells As Main Defense Against Infection	NCT05393505	Neutropenic Fev...	Meropenem Injec... Levofloxacin Amoxicillin Cla... Antibiotic	18 Years -	The University of Hong Kong
Timing of Acute Palliative Care Consultation in Critically Ill Patients	NCT02858778	Multiple Organ ... End Stage Cardi... End Stage Chron... Chronic Kidney ... Hepatic Encepha... Sepsis Dementia Multiple Sclero... Parkinson's Dis... In-Hospital Car... Solid Organ Can...	Early order of ...	65 Years -	Wayne State University
Fentanyl for Breakthrough Pain in the Emergency Department	NCT01812759	Pain	Fentanyl Nasal ... Hydromorphone P... Placebo Nasal S...	18 Years - 75 Years	M.D. Anderson Cancer Center
Assessment of Cancer Pain in Emergency Department in Traditional Chinese Medicine	NCT02116218	Neoplasms Pain	acupuncture Vaccaria seed	20 Years - 75 Years	Changhua Christian Hospital

Spots Global Cancer Trial Database for emergency department