Optimizing the Use of Ketamine to Reduce Chronic Postsurgical Pain

NCT ID: NCT05037123

Last Updated: 2025-06-25

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 765 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-04
• Study Completion Date: 2026-08-31

Brief Summary

The study utilizes a 3-arm placebo-controlled RCT to study the effectiveness of ketamine in reducing chronic post-mastectomy pain. Participants randomized to the first arm will receive a 0.35 mg/kg dose after induction, followed by a 0.25 mg/kg/hr infusion during surgery (up to a maximum of 6 hours) and continued for 2 hours postoperatively. Participants in the second arm will receive a single dose of 0.6 mg/kg of ketamine in the post-anesthesia care unit, and the final group will serve as the control group and receive saline (no ketamine).

Detailed Description

This is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial to study the effectiveness of ketamine in reducing PMPS. In a 3-arm, parallel-group study, approximately 750 adult women undergoing mastectomy or prophylactic mastectomy for oncologic reasons will be randomized to one of three arms. Participants in the first arm will receive continuous ketamine infusion starting after anesthetic induction (0.35 mg/kg dose after induction, followed by a 0.25 mg/kg/hr infusion during surgery (with a maximum infusion of 6 hours) plus a postoperative saline dose, and continuation of 0.25 mg/kg/hr ketamine infusion for 2 hours postoperatively). Participants in the second arm will receive a dose of saline after induction, followed by a saline infusion during the surgery plus a single dose of 0.6 mg/kg of ketamine in the PACU, and 2 hours of saline infusion after surgery. The final group will serve as the control group and receive an intraoperative dose of saline, followed by saline infusion plus a postoperative saline dose and 2 hours of saline infusion after surgery. Participants will be followed at 1 and 7 days and 1, 3, 6, and 12 months after surgery.

Conditions

Chronic Postsurgical Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: TRIPLE

Study Groups

Arm 1 Continuous ketamine infusion group

Continuous ketamine infusion (0.35 mg/kg after induction, followed by 0.25 mg/kg/hr until 2 hours after surgery) plus saline IV dose in post-anesthesia care unit

Group Type: ACTIVE_COMPARATOR

Continuous ketamine infusion

Intervention Type: DRUG

Continuous ketamine infusion (0.35 mg/kg after induction, followed by 0.25 mg/kg/hr until 2 hours after surgery) plus saline IV dose in post-anesthesia care unit

Arm 2 Ketamine + Saline group

Saline dose and infusion intraoperatively, then single-dose IV ketamine (0.60 mg/kg) in post-anesthesia care unit plus 2 hours of saline administration after surgery

Group Type: ACTIVE_COMPARATOR

Ketamine + Saline

Intervention Type: DRUG

Saline dose and infusion intraoperatively, then single-dose IV ketamine (0.60 mg/kg) in post-anesthesia care unit plus 2 hours of saline administration after surgery

Arm 3 Placebo group

Placebo, Saline dose and infusion intraoperatively, then saline IV dose in post-anesthesia care unit plus 2 hours of saline administration after surgery

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo, Saline dose and infusion intraoperatively, then saline IV dose in post-anesthesia care unit plus 2 hours of saline administration after surgery

Interventions

Continuous ketamine infusion

Continuous ketamine infusion (0.35 mg/kg after induction, followed by 0.25 mg/kg/hr until 2 hours after surgery) plus saline IV dose in post-anesthesia care unit

Intervention Type: DRUG

Ketamine + Saline

Saline dose and infusion intraoperatively, then single-dose IV ketamine (0.60 mg/kg) in post-anesthesia care unit plus 2 hours of saline administration after surgery

Intervention Type: DRUG

Placebo

Placebo, Saline dose and infusion intraoperatively, then saline IV dose in post-anesthesia care unit plus 2 hours of saline administration after surgery

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Woman 18 years of age or older
• Undergoing elective breast surgery for oncologic indication as follows: unilateral or bilateral mastectomy, prophylacticmastectomy, +/- lymph node dissection, +/- immediate or delayed reconstruction.
• No distant metastases

Exclusion Criteria

• History of cognitive impairment or clinical signs of altered mental status (AMS) that may interfere with adherence to study procedures and/or participant safety. Clinical signs of AMS may include but are not limited to: confusion, amnesia, disorientation, fluctuating levels of alertness, etc.
• Past ketamine or phencyclidine misuse or abuse
• Schizophrenia or history of psychosis
• History of post-traumatic stress disorder
• Known sensitivity or allergy to ketamine
• Liver or renal insufficiency
• History of uncontrolled hypertension, chest pain, cardiac arrhythmia, stroke, head trauma, intracranial mass or hemorrhage, glaucoma, porphyria, uncontrolled thyroid disease, or other contraindication to ketamine
• Lamotrigine, alfentanil, physostigmine, or 4-aminopyridine use
• Currently Pregnant
• Body mass index (BMI) equal to or greater than 41
• Non-English or non-Spanish speaker
• Currently participating in another pain interventional trial
• Unwilling to comply with all study procedures and be available for the duration of the study
• Patient is American Society of Anesthesiologists (ASA) physical status 4, 5, or 6
• Patient has started or undergone hormone therapy for gender transition into male.
• Patient scheduled for any bilateral (or greater) flap reconstruction

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jing Wang, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Lisa Doan, MD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of Arkansas

Little Rock, Arkansas, United States

Rush University Medical Center

Chicago, Illinois, United States

Brigham and Women's Hospital - Harvard University

Chestnut Hill, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University at St. Louis Medical Center

St Louis, Missouri, United States

NYU Langone Health (Tisch Hospital, Kimmel Pavilion)

New York, New York, United States

New York Presbyterian Columbia University Irving Medical Center

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Montefiore Medical Center - Albert Einstein College of Medicine

The Bronx, New York, United States

University of Pittsburgh - Magee Women's Hospital

Pittsburgh, Pennsylvania, United States

University of Texas - Southwestern Medical Center

Dallas, Texas, United States

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

University of Washington Medical Center

Seattle, Washington, United States

Countries

United States

References

Wang J, Doan LV, Axelrod D, Rotrosen J, Wang B, Park HG, Edwards RR, Curatolo M, Jackman C, Perez R; NCATS Trial Innovation Network. Optimizing the use of ketamine to reduce chronic postsurgical pain in women undergoing mastectomy for oncologic indication: study protocol for the KALPAS multicenter randomized controlled trial. Trials. 2024 Jan 19;25(1):67. doi: 10.1186/s13063-023-07884-y.

Reference Type: DERIVED

PMID: 38243266 (View on PubMed)

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

21-00715

Identifier Type: -

Identifier Source: org_study_id