UH3CA261067

Optimizing the Use of Ketamine to Reduce Chronic Postsurgical Pain - Project Summary

Chronic pain contributes significantly to the current opioid epidemic. Up to 20% of postoperative patients develop chronic postsurgical pain (CPSP). CPSP is highly associated with chronic opioid use and dependence, and yet routine multimodal analgesia as a combination of acetaminophen, NSAIDs, and anti-neuropathic agents is only moderately effective in preventing CPSP.

The incidence for CPSP is particularly high in patients undergoing mastectomy or breast conserving surgery with lymph node dissections (25-60%). This specific postsurgical pain condition is known as post-mastectomy pain syndrome (PMPS), and a recent study showed that 1 in 10 patients continue to use opioids 3 months after surgery.

We aim to study the effectiveness of perioperative ketamine for the prevention of PMPS, within the NIH HEAL Pain Management Effectiveness Research Network (PAIN ERN). Our rationale is that ketamine can reduce key risks for CPSP including acute pain severity, anxiety and depression, and pain catastrophizing, and in doing so can prevent the development of PMPS. Mechanistically, ketamine is known to enhance endogenous cortical control of pain and mood.

There is strong clinical evidence for perioperative ketamine infusion in reducing postsurgical pain, and for a single ketamine bolus (0.3-0.5mg/kg) to treat depression and anxiety associated with postsurgical pain. However, studies are urgently needed to test the efficacy of ketamine in the perioperative period for preventing CPSP, particularly PMPS, in a large cohort of patients and to assess clinical variables predictive for chronic pain severity and for treatment effects.

We aim to conduct a multi-site, three-arm RCT to study the effectiveness of ketamine in reducing the incidence and severity of PMPS. 750 adult women after mastectomy or breast conserving surgery with lymph node dissection will be randomized to receive either a standard continuous ketamine infusion starting after induction (bolus of 0.35mg/kg followed by infusion at the rate of 0.30mg/kg/hr) and continued for 2 hours after surgery, a regimen of single-bolus ketamine (0.6mg/kg) administered right after surgery, or placebo (saline) control.

To maintain the pragmatic nature of an effectiveness trial, all patients will receive routine postoperative multimodal analgesia. Compatible with recent NIH recommendations, we will assess pain, function, and mood over 12 months after surgery. We will use Brief Pain Inventory (BPI) severity score at 3 months after surgery as primary endpoints. Secondary endpoints include pain incidence, BPI, Short-Form McGill's Pain Questionnaire, opioid use, NIH PROMIS scales, Hospital Anxiety and Depression Scale, pain catastrophizing scale, and Breast Cancer Pain Questionnaire. We will also build precision medicine models to analyze clinical variables associated with CPSP and with the success of ketamine treatment.

Agreements have been reached with 12 sites, including 7 Clinical and Translational Science Awards (CTSA) hubs, NYU, Columbia, Einstein, BWH, MSKCC, Washington University at St. Louis, Duke, and Univ. Washington, to carry out this study successfully.

New York University

TO SUPPORT BASIC AND CLINICAL NEUROSCIENCE, BIOMEDICAL, BEHAVIORAL AND SOCIAL SCIENCE, EPIDEMIOLOGIC, HEALTH SERVICES AND HEALTH DISPARITY RESEARCH. TO DEVELOP NEW KNOWLEDGE AND APPROACHES RELATED TO THE PREVENTION, DIAGNOSIS, TREATMENT, ETIOLOGY, AND CONSEQUENCES OF DRUG ABUSE AND ADDICTION, INCLUDING HIV/AIDS. TO SUPPORT RESEARCH TRAINING AND RESEARCH SCIENTIST DEVELOPMENT. TO SUPPORT DISSEMINATION OF RESEARCH FINDINGS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) LEGISLATION IS INTENDED TO EXPAND AND IMPROVE THE SBIR PROGRAMS TO EMPHASIZE AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF TECHNOLOGY DEVELOPED THROUGH FEDERAL SBIR RESEARCH AND DEVELOPMENT, INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN THE SBIR PROGRAM. THE LEGISLATION INTENDS THAT THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.279 - Drug Abuse and Addiction Research Programs

National Cancer Institute (NCI) [HHS - NIH]

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

New York, New York 10016 United States

Single Zip Code

HEAL Initiative: Pain Management Effectiveness Research Network: Clinical Trial Planning and Implementation Cooperative Agreement (UG3/UH3 Clinical Trial Required) (RFA-NS-20-028)

Amendment Since initial award the total obligations have increased 315% from $1,281,438 to $5,322,917.