Clinical trial NCT05037123: Optimizing the Use of Ketamine to Reduce Chronic Postsurgical Pain
Official title: Optimizing the Use of Ketamine to Reduce Chronic Postsurgical Pain
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Chronic Postsurgical Pain
Keywords: Mastectomy
Post-Mastectomy
Ketamine
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2021-09-08
Enrollment: 765
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: BPI pain severity subscale score
timeFrame: 3 months
Secondary outcomes:
measure: BPI pain severity and pain interference subscales score
timeFrame: Baseline, 1 and 7 days and 1, 3*, 6, and 12 months after surgery
measure: Incidence of PMS: BPI average pain score
timeFrame: Baseline, 3, 6, and 12 months after surgery
measure: Pain in the surgical site (chest wall, axilla, and/or arm): BCPQ Score
timeFrame: 7 days and 1, 3, 6, and 12 months after surgery
measure: PROMIS Depression and Anxiety Short Form Scores
timeFrame: Baseline, 7 days and 1, 3, 6, and 12 months after surgery
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas
state: Arkansas
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chestnut Hill
country: United States
facility: Brigham and Women's Hospital - Harvard University
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University at St. Louis Medical Center
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center - Albert Einstein College of Medicine
state: New York
city: New York
country: United States
facility: NYU Langone Health (Tisch Hospital, Kimmel Pavilion)
state: New York
city: New York
country: United States
facility: New York Presbyterian Columbia University Irving Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh - Magee Women's Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas - Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: NYU Langone Health
name: Jing Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: NYU Langone Health
name: Lisa Doan, MD
role: PRINCIPAL_INVESTIGATOR
References: