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).
Brief Title
Optimizing the Use of Ketamine to Reduce Chronic Postsurgical Pain
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.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Chronic Postsurgical Pain
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) greater than 35
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
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) greater than 35
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
Inclusion 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
* 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
Gender
Female
Gender Based
false
Keywords
Mastectomy
Post-Mastectomy
Ketamine
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05037123
Org Class
Other
Org Full Name
NYU Langone Health
Org Study Id
21-00715
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Optimizing the Use of Ketamine to Reduce Chronic Postsurgical Pain
Primary Outcomes
Outcome Description
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.
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.
Outcome Measure
BPI pain severity subscale score
Outcome Time Frame
3 months
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Baseline, 1 and 7 days and 1, 3*, 6, and 12 months after surgery
Outcome Measure
BPI pain severity and pain interference subscales score
Outcome Description
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.
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.
Outcome Time Frame
Baseline, 3, 6, and 12 months after surgery
Outcome Measure
Incidence of PMS: BPI average pain score
Outcome Description
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).
Outcome Time Frame
7 days and 1, 3, 6, and 12 months after surgery
Outcome Measure
Pain in the surgical site (chest wall, axilla, and/or arm): BCPQ Score
Outcome Description
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.
Outcome Time Frame
Baseline, 7 days and 1, 3, 6, and 12 months after surgery
Outcome Measure
PROMIS Depression and Anxiety Short Form Scores
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Locked Fields
Render the field
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Shamantha Reddy
Investigator Email
shreddy@montefiore.org