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

Primary Purpose

Chronic Postsurgical Pain

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Continuous ketamine infusion
Ketamine + Saline
Placebo
Sponsored by
NYU Langone Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Chronic Postsurgical Pain focused on measuring Mastectomy, Post-Mastectomy, Ketamine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept 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) 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

Sites / Locations

  • University of Alabama at BirminghamRecruiting
  • University of ArkansasRecruiting
  • Rush University Medical CenterRecruiting
  • Brigham and Women's Hospital - Harvard UniversityRecruiting
  • Mayo ClinicRecruiting
  • Washington University at St. Louis Medical CenterRecruiting
  • Montefiore Medical Center - Albert Einstein College of MedicineRecruiting
  • NYU Langone Health (Tisch Hospital, Kimmel Pavilion)Recruiting
  • New York Presbyterian Columbia University Irving Medical CenterRecruiting
  • Memorial Sloan Kettering Cancer CenterRecruiting
  • University of Pittsburgh - Magee Women's HospitalRecruiting
  • University of Texas - Southwestern Medical CenterRecruiting
  • University of Texas - MD Anderson Cancer CenterRecruiting
  • University of Washington Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

Arm 1 Continuous ketamine infusion group

Arm 2 Ketamine + Saline group

Arm 3 Placebo group

Arm 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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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).
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.

Full Information

First Posted
August 31, 2021
Last Updated
August 7, 2023
Sponsor
NYU Langone Health
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT05037123
Brief Title
Optimizing the Use of Ketamine to Reduce Chronic Postsurgical Pain
Acronym
KALPAS
Official Title
Optimizing the Use of Ketamine to Reduce Chronic Postsurgical Pain
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 4, 2022 (Actual)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
October 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Postsurgical Pain
Keywords
Mastectomy, Post-Mastectomy, Ketamine

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
Participants, study members, and treating clinicians will be blinded to intervention.
Allocation
Randomized
Enrollment
750 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 1 Continuous ketamine infusion group
Arm Type
Active Comparator
Arm 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
Arm Title
Arm 2 Ketamine + Saline group
Arm Type
Active Comparator
Arm 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
Arm Title
Arm 3 Placebo group
Arm Type
Placebo Comparator
Arm Description
Placebo, Saline dose and infusion intraoperatively, then saline IV dose in post-anesthesia care unit plus 2 hours of saline administration after surgery
Intervention Type
Drug
Intervention Name(s)
Continuous ketamine infusion
Intervention 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
Intervention Type
Drug
Intervention Name(s)
Ketamine + Saline
Intervention 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
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo, Saline dose and infusion intraoperatively, then saline IV dose in post-anesthesia care unit plus 2 hours of saline administration after surgery
Primary Outcome Measure Information:
Title
BPI pain severity subscale score
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.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
BPI pain severity and pain interference subscales score
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.
Time Frame
Baseline, 1 and 7 days and 1, 3*, 6, and 12 months after surgery
Title
Incidence of PMS: BPI average pain score
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.
Time Frame
Baseline, 3, 6, and 12 months after surgery
Title
Pain in the surgical site (chest wall, axilla, and/or arm): BCPQ Score
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).
Time Frame
7 days and 1, 3, 6, and 12 months after surgery
Title
PROMIS Depression and Anxiety Short Form Scores
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.
Time Frame
Baseline, 7 days and 1, 3, 6, and 12 months after surgery

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jing Wang, MD, PhD
Phone
212-263-5072
Email
Jing.Wang2@nyulangone.org
First Name & Middle Initial & Last Name or Official Title & Degree
Randy Cuevas, MPA
Phone
2122631538
Email
Randy.Cuevas@nyulangone.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jing Wang, MD, PhD
Organizational Affiliation
NYU Langone Health
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lisa Doan, MD
Organizational Affiliation
NYU Langone Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lily Gutnik, MD, MPH
Phone
205-934-3562
Email
lgutnik@uabmc.edu
First Name & Middle Initial & Last Name & Degree
Lily Gutnik, MD, MPH
Facility Name
University of Arkansas
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jill Mhyre, MD
Phone
501-686-6119
Email
JMMhyre@uams.edu
First Name & Middle Initial & Last Name & Degree
Jill Mhyre, MD
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Asokumar Buvanendran, MD
Phone
312-942-3685
Email
asokumar_buvanendran@rush.edu
First Name & Middle Initial & Last Name & Degree
Asokumar Buvanendran, MD
Facility Name
Brigham and Women's Hospital - Harvard University
City
Chestnut Hill
State/Province
Massachusetts
ZIP/Postal Code
02467
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kristin Schreiber, MD, PhD
Phone
617-732-9463
Email
klschreiber@bwh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Kristin Schreiber, MD, PhD
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
William Hooten, MD
Phone
507-266-9670
Email
hooten.william@mayo.edu
First Name & Middle Initial & Last Name & Degree
William Hooten, MD
Facility Name
Washington University at St. Louis Medical Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Simon Haroutounian, PhD, MSc
Phone
314-273-2240
Email
sharout@wustl.edu
First Name & Middle Initial & Last Name & Degree
Simon Haroutounian, PhD, MSc
Facility Name
Montefiore Medical Center - Albert Einstein College of Medicine
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shamantha Reddy, MD, FASA
Phone
646-942-0519
Email
SHREDDY@montefiore.org
First Name & Middle Initial & Last Name & Degree
Shamantha Reddy, MD, FASA
Facility Name
NYU Langone Health (Tisch Hospital, Kimmel Pavilion)
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
KALPAS Study
Email
kalpas@nyulangone.org
First Name & Middle Initial & Last Name & Degree
Jing Wang, MD, PhD
Facility Name
New York Presbyterian Columbia University Irving Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bret Taback, MD
Phone
212-342-3681
Email
bt2160@cumc.columbia.edu
First Name & Middle Initial & Last Name & Degree
Bret Taback, MD
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joshua Mincer, MD, PhD
Phone
646-735-8059
Email
mincerj@mskcc.org
First Name & Middle Initial & Last Name & Degree
Joshua Mincer, MD, PhD
Facility Name
University of Pittsburgh - Magee Women's Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Grace Lim, MD, MS
Phone
412-641-2179
Email
limkg2@upmc.edu
First Name & Middle Initial & Last Name & Degree
Grace Lim, MD, MS
Facility Name
University of Texas - Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gloria Cheng, MD
Phone
214-645-7011
Email
Gloria.Cheng@UTSouthwestern.edu
First Name & Middle Initial & Last Name & Degree
Gloria Cheng, MD
Facility Name
University of Texas - MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juan Cata, MD
Phone
832-294-5900
Email
JCata@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Juan Cata, MD
Facility Name
University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michele Curratolo, MD, PhD
Phone
206-543-7817
Email
curatolo@uw.edu
First Name & Middle Initial & Last Name & Degree
Michele Curratolo, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to the PI. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
IPD Sharing Time Frame
Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
IPD Sharing Access Criteria
Requests should be directed to Jing.Wang2@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.

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Optimizing the Use of Ketamine to Reduce Chronic Postsurgical Pain

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