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

NYU Langone Health

Status and phase: Active, not recruiting; Phase 3

Conditions: Chronic Postsurgical Pain

Treatments: Drug: Continuous ketamine infusion; Other: Placebo; Drug: Ketamine + Saline

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05037123

21-00715

Details and patient eligibility

About

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).

Full 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.

Enrollment: 765 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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765 participants in 3 patient groups, including a placebo group

Arm 1 Continuous ketamine infusion group

Active Comparator group

Description:

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

Treatment:

Drug: Continuous ketamine infusion

Arm 2 Ketamine + Saline group

Active Comparator group

Description:

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

Treatment:

Drug: Ketamine + Saline

Arm 3 Placebo group

Placebo Comparator group

Description:

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

Treatment:

Other: Placebo