Nervous System Diseases

Symptoms and General Pathology

All Conditions

Immune System Diseases

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Neoplasms

Digestive System Diseases

Rare Diseases

Neuralgia

Peripheral Nervous System Diseases

Pain

Hypersensitivity

Respiratory Tract Infections

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neuromuscular Diseases

Neurologic Manifestations

Familial Cold Autoinflammatory Syndrome

Anti-Arrhythmia Agents

Channel Blockers

Central Nervous System Depressants

All Drugs and Chemicals

Pharmaceutical Solutions

Micronutrients

Antineoplastic Agents

Lidocaine

Leucovorin

Fluorouracil

Oxaliplatin

Anesthetics

Anesthetics, Local

Sodium Channel Blockers

Diuretics, Potassium Sparing

Intravenous infusion of D5W solution over a 130 minute period.

FOLFOX:

Oxaliplatin 85mg/m2 IV over 2h, Leucovorin 400 mg/m2 IV over 2h, 5-FU 400mg/m2 IV bolus, followed by a 1200mg/m2/day continuous infusion for 2 days.

Intravenous infusion of lidocaine hydrochloride solution in D5W over a 130 minute period.

FOLFOX:

Oxaliplatin 85mg/m2 IV over 2h, Leucovorin 400 mg/m2 IV over 2h, 5-FU 400mg/m2 IV bolus, followed by a 1200mg/m2/day continuous infusion for 2 days.

Intravenous lidocaine will be dosed as a brief 1 mg/kg infusion (based on Ideal Body Weight (IBW)) over 10 minutes, followed by a 0.04 mg/kg/min infusion over additional 120 minutes, resulting in a total dose of 5.8 mg/kg IBW.

If this dose is tolerable in four consecutive sessions of mFOLFOX6 in six or more of the eight patients in the tolerability phase, we will initiate the randomized efficacy pilot study.

Lidocaine Hydrochloride

Dextrose 5% in water will be administered as active comparator.

Placebo

Each cycle (repeated every 14 days):

Oxaliplatin 85mg/m2 IV over 2h, Leucovorin 400 mg/m2 IV over 2h, 5-FU 400mg/m2 IV bolus, followed by a 1200mg/m2/day continuous infusion for 2 days.

FOLFOX regimen

Simon Haroutounian, PhD

Oxaliplatin-induced neuropathy is a major dose-limiting side effect in patients with colorectal cancer treated with the FOLFOX chemotherapy regimen. Hypersensitivity to cold is the sensory hallmark of oxaliplatin-induced neuropathy, and it can predict the development of long-term neuropathy. In this study, the investigators aim to determine whether intravenous lidocaine can prevent oxaliplatin-induced cold hypersensitivity.

Colorectal cancer is the third leading cause of cancer death in the United States, with an estimated incidence of 130.000 cases per year. Oxaliplatin is the first-line chemotherapy regimen for gastro-intestinal cancers. Despite its efficacy, oxaliplatin causes peripheral neuropathy in 72% of the treated patients. Acute oxaliplatin-induced peripheral neuropathy \[OIPN\] is the most common dose-limiting side effect of oxaliplatin and characterized by profound cold allodynia in the extremities. In about 21% of the patients acute OIPN exacerbates into chronic neuropathic pain, which is treatment resistant to currently approved drugs, pointing towards a great need to identify an effective strategy in preventing OIPN. Recent literature suggests that certain methods of assessing sensory nerve function in neuropathic pain patients may provide a prediction to an individual analgesic response; however, no placebo-controlled studies have been performed with the primary goal of identifying treatment response predictors in preventing OIPN.

In this pilot study we will both determine the tolerability and the efficacy of intravenous Lidocaine, for preventing oxaliplatin-induced cold hypersensitivity in the setting of mFOLFOX6 chemotherapy for advanced colorectal cancer.

The proposed study will be conducted in two phases. The tolerability phase is an open-label study to determine the tolerable dose regimen of IV lidocaine in patients with advanced colorectal cancer receiving oxaliplatin chemotherapy. The efficacy pilot phase is a randomized, double-blinded, controlled study comparing the outcomes between IV lidocaine versus placebo in the same setting of colorectal cancer. Consented subjects will attend a screening visit and six intervention visits, during which they will undergo sensory testing and receive intravenous lidocaine or placebo infusion. Cold hypersensitivity and spontaneous pain will be assessed at baseline, daily for 12 weeks and at follow-up visits. At enrollment, each patient will be assigned a study number, which will match a previously prepared computer-generated list of randomization numbers to determine the interventions lidocaine or placebo. The participants and all other study personnel will be blinded to the treatment allocation.

Tolerability phase: prospective, open-label Efficacy pilot study: randomized, parallel, double blind, placebo controlled

At enrollment, each patient will be assigned a study number, which will match a previously prepared computer-generated list of randomization numbers to determine the interventions. The participants and all other study personnel will be blinded to the treatment allocation.

Lidocaine for Oxaliplatin-induced Neuropathy

Intravenous Lidocaine for Preventing Painful Oxaliplatin-induced Peripheral Neuropathy (OIPN)

IPD will be shared 6 months after publication of the results in a peer-reviewed journal, upon submission of a robust data analysis plan to the study investigators.

The intensity of cold pain and cold unpleasantness is evaluated separately, assessed daily on a 0-10 scale, upon holding a pre-cooled (\~8°C) metal cylinder for 10 seconds. the area under the curve of cold pain and cold unpleasantness vs time is calculated per chemotherapy cycle (every two weeks) and serves as a primary outcome measure.

For intervention (lidocaine+FOLFOX) and control (placebo+FOLFOX) groups, the average of cold pain AUC and cold unpleasantness AUC over 7 cycles was calculated. The average AUCs over 7 cycles were compared between study arms.

The AUC is measured as a score on a 0-10 scale multiplied by 14 days and may range between 0 and 140. Higher AUC values represent more intense cold pain/unpleasantness.

Change in CIPN (Chemotherapy-induced peripheral Neuropathy) score (on EORTC QLQ-CIPN20 tool ) from baseline to the Cycle 6 (12 weeks), and from baseline to last follow-up (34-36 weeks). EORTC QLQ-CIPN20 ranges from 0 (no symptoms) to 100 (worst symptoms). A higher score represents worse neuropathy. The changes in scores are compared between study arms.

EORTC QLQ-CIPN20 tool is a quality of life questionnaire (QLQ) from the European Organization for Research and Treatment of Cancer (EORTC) for evaluation of CIPN.

Changes in Neuropathic Pain Symptom Inventory (NPSI) descriptors of neuropathic pain over time from baseline to cycle 3(6 weeks), cycle 6 (12 weeks), and the last follow-up (34-36 weeks). The total NPSI score ranges from 0 to 100; a higher NPSI total score represents a worse neuropathy outcome. The changes in scores from baseline are compared between study arms.

The cumulative dose of oxaliplatin received over the course (up to 12 cycles) of mFOLFOX6 treatment regimen. It corresponds to the absolute summed up quantity of Oxaliplatin administered to the patient over time. There is no range for this measure. Since this is a dose-limiting neuropathy prevention study, the higher value can be interpreted as better outcome.

Washington University School of Medicine

Assistant Professor of Anesthesiology

Adverse Event: any unfavorable medical occurrence in a human subject including any abnormal sign, symptom, or disease.

For the purposes of this protocol, all adverse events will be collected and documented on CRFs by questionnaire.

Intravenous infusion of D5W solution over a 130 minute period.

FOLFOX:

Oxaliplatin 85mg/m2 IV over 2h, Leucovorin 400 mg/m2 IV over 2h, 5-FU 400mg/m2 IV bolus, followed by a 1200mg/m2/day continuous infusion for 2 days.

Placebo: Dextrose 5% in water will be administered as active comparator.

FOLFOX regimen: Each cycle (repeated every 14 days):

Oxaliplatin 85mg/m2 IV over 2h, Leucovorin 400 mg/m2 IV over 2h, 5-FU 400mg/m2 IV bolus, followed by a 1200mg/m2/day continuous infusion for 2 days.

Placebo + FOLFOX

Intravenous infusion of lidocaine hydrochloride solution in D5W over a 130 minute period.

FOLFOX:

Oxaliplatin 85mg/m2 IV over 2h, Leucovorin 400 mg/m2 IV over 2h, 5-FU 400mg/m2 IV bolus, followed by a 1200mg/m2/day continuous infusion for 2 days.

Lidocaine Hydrochloride: Intravenous lidocaine will be dosed as a brief 1 mg/kg infusion (based on Ideal Body Weight (IBW)) over 10 minutes, followed by a 0.04 mg/kg/min infusion over additional 120 minutes, resulting in a total dose of 5.8 mg/kg IBW.

If this dose is tolerable in four consecutive sessions of mFOLFOX6 in six or more of the eight patients in the tolerability phase, we will initiate the randomized efficacy pilot study.

FOLFOX regimen: Each cycle (repeated every 14 days):

Oxaliplatin 85mg/m2 IV over 2h, Leucovorin 400 mg/m2 IV over 2h, 5-FU 400mg/m2 IV bolus, followed by a 1200mg/m2/day continuous infusion for 2 days.

Lidocaine + FOLFOX

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

This includes only patients who are enrolled and randomized into 2 groups.

Due to the COVID-19 pandemic, the study finished earlier than planned. The total number of patients enrolled was 26 instead of 30.

Simon Haroutounian, PhD. Associate Professor

Null hypothesis: Average AUC of cold pain score over 14 days of a chemotherapy cycle in the Control group is equal or lower than that of the experimental group. The comparison is for average AUC values over 7 cycles of chemotherapy per patient

Null hypothesis: Cold hypersensitivity counted as unpleasantness score for 14 days after cycle (AUC) in the Control group is less than that of the experimental group. The difference was calculated for the Cycle 6 visit.

pain AUC

unpleasantness AUC

data for 14 days following the 6th cycle was collected and analyzed.

Area Under the Curve (AUC) of Intensity of Oxaliplatin-induced Cold Pain/Unpleasantness vs Time

the null hypothesis is EORTC QLQ-CIPN20 sensory score change in the Control group is equal to or less than that of the experimental group for the last follow-up study visit.

The null hypothesis is EORTC QLQ-CIPN20 sensory score change in the Control group is equal to or less than that of the experimental group for the cycle 6 (12 weeks) follow-up study visit.

34-36 weeks

Patients in each group who had corresponding visit data

CIPN Score on EORTC QLQ-CIPN20

The null hypothesis is NPSI total score in the Control group is equal to or less than that of the experimental group for the C3 (6 weeks) study visit.

The null hypothesis is NPSI total score in the Control group is equal to or less than that of the experimental group for the C6 (12 weeks) study visit.

The null hypothesis is NPSI total score in the Control group is equal to or less than that of the experimental group for the last follow-up study visit.

6 weeks visit

12 weeks visit

last follow-up visit

Changes in NPSI Score.

The null hypothesis is Oxaliplatin cumulative dose in the Control group is equal to or higher than that of the experimental group.

The Cumulative Dose of Oxaliplatin

Overall Study

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Gastrointestinal Agents

Pancrelipase

Pancreatin

The IV bolus and infusions of lidocaine to those patients assigned to the lidocaine group will be started in the operating room and will continue until 24 h later. The group receiving the lidocaine infusion will first be administered a 1.0 - 1.5 mg/kg loading infusion over 5 minutes followed by a 1.0 - 1.5 mg/kg/h infusion for 24 h

The group receiving the saline infusion will be administered an equivalent volume of saline infused over 5 min followed by a saline infusion at the same flow rate as that used in the lidocaine group for 24 h (1.0 - 1.5 mg/kg/hr)

IV Lidocaine a 1.0 - 1.5 mg/kg loading infusion for perioperative pain control

IV Saline a 1.0 - 1.5 mg/kg loading infusion for perioperative pain control

Saline Solution for Injection

Alexandra Barabanova, MS

Gina E. Votta-Velis, MD PhD

Gina E Votta-Velis, MD PhD

E. Gina Votta-Velis, MD PhD

Ajay Rana, PhD

Pier C. Giulianotti, MD

Alain A. Borgeat, MD

Sandeep Kumar, PhD

Antonio Gangemi, MD

Valentina Valle, MD

This study elucidates the effects of the intravenous (IV) lidocaine infusion on the biology of pancreatic circulating tumor cells (CTCs) isolated from patients undergoing robotic pancreatectomy for all types of pancreatic cancer.

A prospective randomized controlled double blinded trial design will be used for the proposed study.

The primary objective of this study is to determine the effect of IV lidocaine infusion on various enzymatic activities and associated pathways in isolated CTCs as well as the number of CTCs during the perioperative period in patients undergoing robotic pancreatectomy for pancreatic cancer. It is expected that by downregulating the pathways by lidocaine might affect the enzymatic activity in those CTCs as well as the number of CTCs in the circulation.

A prospective randomized controlled double blinded trial design will be used for the proposed study.

Patients undergoing robotic pancreatectomy for pancreatic cancer will be randomized (ratio 1:1) into two groups: one group will receive a 24-h normal saline infusion and the second group will receive a 24-h lidocaine infusion. Blood samples will be collected in different times perioperatively in order to evaluate the objectives of the study.

A prospective randomized placebo-controlled double blinded trial design will be used for the proposed study.

Both patients and the physicians performing the cases will be unaware of who receives lidocaine or placebo.

Lidocaine Infusion in Pancreatic Cancer

Lidocaine Infusion in Pancreatic Cancer: Translational Studies in a Preclinical Model And Human Subjects

Src Tyrosine Kinase Enzymatic activity in CTCs. Fluorescence intensity will be used to measure Src phosphorylation in circulating tumor cells.

Upregulation or downregulation of gene expression will be measured with the Real Time (RT) square Profiler Polimerase Chain Reaction (PCR )Array Analysis, and Real Time PCR

University of Illinois at Chicago

Associate Professor

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Carcinoma, Renal Cell

Kidney Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Male Urogenital Diseases

Urologic Neoplasms

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Renal Cell Carcinoma

Anti-Infective Agents

Analgesics

Anti-Bacterial Agents

Analgesics, Opioid

Lidocaine Hydrochloride 0.8% in Dextrose 5% Solution

Lidocaine Hydrochloride and 5% Dextrose Injection, USP is a sterile, nonpyrogenic solution prepared from lidocaine hydrochloride and dextrose in water for injection.

Sodium Chloride Injection USP is sterile, nonpyrogenic, isotonic and contains no bacteriostatic or antimicrobial agents.

0.9% Sodium Chloride Injection

Boris Mraovic, MD

Controlling pain is fundamental during and after surgical procedures. This study examines pain associated with robotic assisted surgery on prostate cancer or a kidney mass. In recent years, the risk of opioids in the postoperative period has gained interest due to the growing epidemic of addiction, dependence, and overdose. In this study, the investigators expect a continuous infusion of intravenous lidocaine during the perioperative period to result in less pain and less opioid use.

In recent years, the risk of opioids in the post-operative period has gained interest due to the growing epidemic of addiction, dependence, and overdose. The rate of drug overdose secondary to opioids has continued to increase at an alarming rate. This has been a primary point of concern in all fields of medicine and Urology has not been an exception. This is also a nationwide government and public health concern. This has generated an increased focus on the use of non-opioid analgesics after surgery such as intravenous lidocaine.

Opioids remain the primary source of relief for postoperative pain and have the potential to lead to significant morbidity. Opioids may delay recovery following surgery and have many well-known adverse effects including, but not limited to, nausea, vomiting and prolonged post-operative ileus. Furthermore, in one study, they inadequately provided pain control in 50-60% of postoperative participants. This is a frequent report of participants because of the less than optimal utilization of the medications in fear of their dose dependent adverse effects and various contraindications. On the other hand, surplus medication following surgery is another prominent component of the opioid problem in Urologic practices. Bates et al. found that of the 586 participants that underwent a urological procedure that they reviewed, 67% of them had collected surplus medication. It is both necessary and beneficial for surgeons and participants to utilize dose-sparing strategies following surgery to decrease overall opioid usage and outpatient requirement.

One mechanism that has already been employed for overall improvement in prostatectomies and partial nephrectomies is the use of the robotic assisted approach. Robot assisted partial nephrectomies (RALPN) and robotic assisted laparoscopic prostatectomies (RALP) are becoming a mainstay in urologic surgery and increasing annually. This coincides with a continuous downward trend of laparoscopic and open urologic procedures. RALPN has been shown in a meta-analysis to be more favorable than laparoscopic partial nephrectomies and will continue to be the surgical procedure of choice in the near future. RALP is also now the dominant surgical approach while open and laparoscopic prostatectomies becoming less frequent. Robotic assisted surgery is associated with improved functional outcomes, pain scores, shorter hospital stays, and increases in participants satisfaction in many studies.

While there has been a pronounced increase in robotic surgery over the past 10 years that has demonstrated benefits for participants, there has been limited studies regarding the pain management for these participants. Robotic assisted surgery itself decreases pain levels compared to other approaches, but participants continue to experience mild to moderate pain levels in the postoperative period, which are classically managed with NSAIDs and opioids.

Recently, Enhanced Recovery after Surgery protocols (ERAS) have been implemented in an attempt to decrease pain and opioid use as one outcome. ERAS utilizes multimodal analgesia and has shown improvement of participant satisfaction and perioperative opioid use. Systemic lidocaine is becoming more popular and regularly applied through this protocol and, other practices, in due to its analgesic, anti-hyperalgesia and anti-inflammatory properties that it contains. Systemic lidocaine mechanism of action is not fully understood, but it appears to be multifaceted. Systemic lidocaine inhibits voltage-gated sodium channels in both the peripheral and central nervous system. This is believed to cause an additive effect when combined with inhaled anesthetics which also work on the voltage-gated sodium channels in the central nervous system. Despite this summative effect, this is likely not the primary mechanism of action. Instead, it is believed to predominantly act on anti-inflammatory signaling and through inhibiting neuronal effects. Additionally, it reduces nociception and cardiovascular response to surgical stress and pain.

This is a prospective, randomized, double-blinded, placebo-controlled clinical trial on lidocaine infusion for pain control and opioid consumption in participants undergoing either robotic-assisted laparoscopic prostatectomy or robotic-assisted laparoscopic partial nephrectomy at University of Missouri Hospital. Participants will be randomized in a 1:1 fashion and stratified by the type of surgery to receive a perioperative intravenous 0.8% lidocaine infusion at 1 mg/kg/h if \< age 65 and 0.5 mg/kg/h if ≥ age 65 or an equal volume and rate of normal saline as a placebo. The infusion will be started 15 minutes after endotracheal intubation and continue for 24 hours.

The study that the investigators propose targets an area of urology that is underrepresented in the current literature despite its increasing importance. To the best of the investigator's knowledge, this has not been directly studied before, although it has been utilized numerous times in the ERAS protocol at the University of Missouri Hospital throughout the Division of Urology and Anesthesiology \& Perioperative Medicine in participants undergoing robotic surgery. The benefits of intravenous lidocaine have been demonstrated in other areas and these results warrant a prospective, randomized, double-blinded, placebo controlled study to assess the lidocaine infusion effects for robot assisted laparoscopic prostatectomies and partial nephrectomies. As the number of robotic assisted surgeries and emphasis on opioid reduction continues, the evaluation of systemic lidocaine will be important in improving outcomes in urology.

Participants will receive either intraoperative 0.8% lidocaine or normal saline at 1 mg/kg/h when younger than 65 years and 0.5 mg/kg/h when greater than or equal to the age of 65 to be delivered by continuous infusion for 24 hours.

The surgeon, anesthesiologist, operating room staff, participant, personnel in the postanesthesia care unit (PACU) as well as the investigators collecting the postoperative data will be blinded to the group allocation. Study medication is prepared and masked by an unblinded investigation drug pharmacist who is not involved in clinical care.

Effect of Perioperative Intravenous Lidocaine Infusion in Robotic-Assisted Urologic Surgery

A Prospective, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial Evaluating the Use of Perioperative Intravenous Lidocaine Infusion to Decrease Pain Scores and Opioid Consumption After Robotic-Assisted Prostatectomy and Robotic-Assisted Partial Nephrectomy

10-cm Visual Analog Scale (VAS), score of 0 "no pain" to a score of 10 "worst pain ever"

Difference in opioid consumption in first 24 hours, discharge and 21 days post-operatively (morphine equivalents)

Difference in length of hospital stay determined by surgeon excluding social factors that may delay discharge

Difference in post-operative Ileus duration

Difference in time in the Post Anesthesia Care Unit (PACU) after surgery

Difference in return of flatus after surgery

Difference in time to out of bed to chair after surgery

Difference in time to first ambulation in the hallway after surgery

University of Missouri-Columbia

Professor of Clinical Anesthesiology

The study followed the ClinicalTrials.gov definitions of adverse/serious adverse events for collection of information.

Lidocaine Hydrochloride infusion

The treatment group received a perioperative and intraoperative infusion of 0.8% lidocaine at 1mg/kg/h.

Treatment Group

Normal saline

The control group received normal saline.

Control Group

11 patients were randomized into the treatment group, while 10 patients were randomized to the control group. Investigators were blinded to the randomization.

Dr Boris Mraovic

Pain 1 hour post operative

Pain 2 hours post operative

Pain 4 hours post operative

Pain 6 hours post operative

Pain 12 hours post operative

Pain 24 hours post operative

Pain 48 hours post operative

Pain 72 hours post operative

Pain 96 hours post operative

Pain 120 hours post operative

Pain on discharge

Pain at post operative visit

Patients were discharged at different times post operatively, dependent on the procedure performed and post operative pain management. Some patients were discharged before 24 hours post operatively.

Difference in Post-operative Pain Scores Measured by Visual Analog Scale

Milligram morphine equivalent (MME) 0-24h postop

Milligram morphine equivalent (MME) 25-48h postop

Milligram morphine equivalent (MME) 49-72h postop

Milligram morphine equivalent (MME) 73-96h postop

Milligram morphine equivalent (MME) 97-120h postop

Milligram morphine equivalent (MME) prescribed at discharge for home use

Milligram morphine equivalent (MME) used of discharge prescription

The milligram morphine equivalent for oral opioid use is reported per group for 24h postop, 25-48h postop, 49-72h postop, 73-96h postop, and 97-120h postop.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Lidocaine for Oxaliplatin-induced Neuropathy	NCT03254394	Neuropathy, Pai... Chemotherapy-in... Colorectal Canc...	Lidocaine Hydro... Placebo FOLFOX regimen	18 Years -	Washington University School of Medicine
Lidocaine Infusion in Pancreatic Cancer	NCT04048278	Pancreatic Canc...	Lidocaine Hydro... Saline Solution...	18 Years -	University of Illinois at Chicago
Effect of Perioperative Intravenous Lidocaine Infusion in Robotic-Assisted Urologic Surgery	NCT03824808	Kidney Cancer Prostate Cancer	Lidocaine Hydro... 0.9% Sodium Chl...	18 Years -	University of Missouri-Columbia
Effect of Perioperative Intravenous Lidocaine Infusion in Robotic-Assisted Urologic Surgery	NCT03824808	Kidney Cancer Prostate Cancer	Lidocaine Hydro... 0.9% Sodium Chl...	18 Years -	University of Missouri-Columbia

Spots Global Cancer Trial Database for lidocaine hydrochloride