Optimizing the Use of Ketamine to Reduce Chronic Postsurgical Pain (KALPAS)

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Postsurgical Pain
• Intervention / Treatment: Drug: Continuous ketamine infusion; Drug: Ketamine + Saline; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 765
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Massachusetts
    • Chestnut Hill, Massachusetts, United States, 02467
      • Brigham and Women's Hospital - Harvard University
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University at St. Louis Medical Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10016
      • NYU Langone Health (Tisch Hospital, Kimmel Pavilion)
    • New York, New York, United States, 10032
      • New York Presbyterian Columbia University Irving Medical Center
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center - Albert Einstein College of Medicine
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh - Magee Women's Hospital
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas - Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • University of Texas - MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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	Drug: 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
Active Comparator: 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	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
Placebo Comparator: 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	Other: Placebo; Placebo, Saline dose and infusion intraoperatively, then saline IV dose in post-anesthesia care unit plus 2 hours of saline administration after surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BPI pain severity subscale score	The Brief Pain Inventory short form (BPI) pain severity subscale assesses pain at its worst, least, average, and current in the past 24 hours. The score ranges from 0 to 10 for each item. The average of the four items will be used. The BPI scale defines pain as follows: Worst Pain Score: 1 - 4 = Mild Pain. Worst Pain Score: 5 - 6 = Moderate Pain. Worst Pain Score: 7 - 10 = Severe Pain.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BPI pain severity and pain interference subscales score	BPI assesses pain severity and interference. The interference subscale measures how much pain has interfered with general activities such as walking and working. Additionally, it inquires about interference in mood, enjoyment of life, relationships, and sleep. The BPI scale defines pain as follows: Worst Pain Score: 1 - 4 = Mild Pain. Worst Pain Score: 5 - 6 = Moderate Pain. Worst Pain Score: 7 - 10 = Severe Pain.	Baseline, 1 and 7 days and 1, 3*, 6, and 12 months after surgery
Incidence of PMS: BPI average pain score	The BPI pain severity subscale assesses pain at its worst, least, average, and current in the past 24 hours. We will use participant's average pain item to assess incidence of PMPS. A score greater than 3 (0-10 scale) will be considered clinically meaningful chronic pain.	Baseline, 3, 6, and 12 months after surgery
Pain in the surgical site (chest wall, axilla, and/or arm): BCPQ Score	The Breast Cancer Pain Questionnaire (BCPQ) assesses pain location, frequency, and severity as well as sensory disturbance after breast surgery. The BCPQ queries patients about pain severity (scores 1-10) and frequency (scores 5 [constantly], 4 [daily], 3 [occasionally], 2 [weekly], 1 [monthly], and 0 [never]) in four surgically related body areas (breast, axilla, chest wall, arm).	7 days and 1, 3, 6, and 12 months after surgery
PROMIS Depression and Anxiety Short Form Scores	Anxiety and depressive symptoms are prevalent in patients undergoing surgery for breast cancer and are risk factors for PMPS. The PROMIS assessments are designed to measure anxiety and depression symptoms. Each assessment will generate a raw score based on participant-reported answers, where the raw score is then converted into a t-score ranging from 0-100; higher scores indicate greater symptoms of anxiety and depression.	Baseline, 7 days and 1, 3, 6, and 12 months after surgery

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jing Wang, MD, PhD, NYU Langone Health; Principal Investigator: Lisa Doan, MD, NYU Langone Health

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2022
• Primary Completion (Actual): May 28, 2025
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: August 31, 2021
• First Submitted That Met QC Criteria: August 31, 2021
• First Posted (Actual): September 8, 2021

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Ketamine; Mastectomy; Post-Mastectomy
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Organic Chemicals; Hydrocarbons; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; Ketamine; Sodium Chloride
• Other Study ID Numbers: 21-00715

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to the PI. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: Requests should be directed to Jing.Wang2@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes