KALPAS: Optimizing the Use of Ketamine to Reduce Chronic Postsurgical Pain
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- BPI pain severity subscale score [3 months]
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.
Secondary Outcome Measures
- BPI pain severity and pain interference subscales score [Baseline, 1 and 7 days and 1, 3*, 6, and 12 months after surgery]
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.
- Incidence of PMS: BPI average pain score [Baseline, 3, 6, and 12 months after surgery]
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.
- Pain in the surgical site (chest wall, axilla, and/or arm): BCPQ Score [7 days and 1, 3, 6, and 12 months after surgery]
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).
- Anxiety and depressed mood: Hospital Anxiety and Depression Scale (HADS) Score [Baseline, 7 days and 1, 3, 6, and 12 months after surgery]
Anxiety and depressive symptoms are prevalent in patients undergoing surgery for breast cancer and are risk factors for PMPS. The HADS is a self-report rating scale of 14 items on a 4-point Likert scale (range 0-3). It is designed to measure anxiety and depression (7 items for each subscale). The total score is the sum of the 14 items, and for each subscale the score is the sum of the respective seven items (ranging from 0-21).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Woman 18 years of age or older
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Undergoing elective breast surgery for oncologic indication as follows: unilateral or bilateral mastectomy, prophylacticmastectomy, +/- lymph node dissection, +/- immediate or delayed reconstruction.
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No distant metastases
Exclusion Criteria:
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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.
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Past ketamine or phencyclidine misuse or abuse
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Schizophrenia or history of psychosis
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History of post-traumatic stress disorder
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Known sensitivity or allergy to ketamine
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Liver or renal insufficiency
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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
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Lamotrigine, alfentanil, physostigmine, or 4-aminopyridine use
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Currently Pregnant
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Body mass index (BMI) greater than 35
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Non-English or non-Spanish speaker
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Currently participating in another pain interventional trial
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Unwilling to comply with all study procedures and be available for the duration of the study
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Patient is American Society of Anesthesiologists (ASA) physical status 4, 5, or 6
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Patient has started or undergone hormone therapy for gender transition into male.
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Patient scheduled for any bilateral (or greater) flap reconstruction
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
| 2 | Brigham and Women's Hospital - Harvard University | Chestnut Hill | Massachusetts | United States | 02467 |
| 3 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 4 | Washington University at St. Louis Medical Center | Saint Louis | Missouri | United States | 63110 |
| 5 | Montefiore Medical Center - Albert Einstein College of Medicine | Bronx | New York | United States | 10467 |
| 6 | NYC Health + Hospitals / Bellevue | New York | New York | United States | 10016 |
| 7 | NYU Langone Health | New York | New York | United States | 10016 |
| 8 | New York Presbyterian Columbia University Irving Medical Center | New York | New York | United States | 10032 |
| 9 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 10 | University of Pittsburgh - Magee Women's Hospital | Pittsburgh | Pennsylvania | United States | 15213 |
| 11 | University of Texas - Southwestern Medical Center | Dallas | Texas | United States | 75390 |
| 12 | University of Texas - MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 13 | University of Washington Medical Center | Seattle | Washington | United States | 98195 |
Sponsors and Collaborators
- NYU Langone Health
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Jing Wang, MD, PhD, NYU Langone Health
- Principal Investigator: Lisa Doan, MD, NYU Langone Health
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 21-00715