Optimizing the Use of Ketamine to Reduce Chronic Postsurgical Pain

Chronic Postsurgical Pain Clinical Trial

— KALPAS  

Official title:

Optimizing the Use of Ketamine to Reduce Chronic Postsurgical Pain

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05037123
• Other study ID #: 21-00715
• Status: Recruiting
• Phase: Phase 3
• Start date: January 4, 2022
• Est. completion date: October 2025

Study information

• Verified date: August 2023
• Source: NYU Langone Health
• Contact: Jing Wang, MD, PhD
• Phone: 212-263-5072
• Email: Jing.Wang2[@]nyulangone.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 750
• Est. completion date: October 2025
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Postsurgical Pain
• Pain, Postoperative

Intervention

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
• 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

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

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Montefiore Medical Center - Albert Einstein College of Medicine	Bronx	New York
United States	Brigham and Women's Hospital - Harvard University	Chestnut Hill	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
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 Arkansas	Little Rock	Arkansas
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	New York Presbyterian Columbia University Irving Medical Center	New York	New York
United States	NYU Langone Health (Tisch Hospital, Kimmel Pavilion)	New York	New York
United States	University of Pittsburgh - Magee Women's Hospital	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University at St. Louis Medical Center	Saint Louis	Missouri
United States	University of Washington Medical Center	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
NYU Langone Health	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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