A Prospective, Randomized Trial of the Effect of Standard of Care Reduced Dose Versus Full Dose Buprenorphine/Naloxone in the Perioperative Period on Pain Control and Post-Operative Opioid Use Disorder Symptoms

The purpose of this research study is to compare two ways of managing pain in people who are taking buprenorphine and are scheduled to undergo surgery. Buprenorphine (subutex) and buprenorphine/naloxone (suboxone) are effective long-term treatments for substance use disorders. The management of pain after surgery in adults taking buprenorphine can be challenging, as buprenorphine may interfere with the effectiveness of other medications used to treat pain.

We want to compare how well pain is managed after surgery ("post-op") in two groups:

The "Continue Group": those who continue taking their standard dose of buprenorphine before, during and after surgery.

The "Reduce Group": those who are placed on a lower dose of buprenorphine starting one day before surgery and during the time period after surgery until the pain from the surgery has decreased. Once the pain from the surgery has decreased, you will be put back on your full dose of buprenorphine.

We also want to find out if there is a difference in pain, opioid cravings, and relapse rates in the month following surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Opioid-use Disorder; Opioid Use Disorder, Mild
• Intervention / Treatment: Drug: Buprenorphine; Drug: Buprenorphine/naloxone

• Study Type: Interventional
• Enrollment (Anticipated): 76
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yi Zhang; Phone Number: 6177246102; Email: mghpainresearch@partners.org
• Study Contact Backup: Name: Sarah Roth; Phone Number: 6177246102; Email: sroth3@mgh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• American Society of Anesthesiologists (ASA) health class I-III
• Currently taking buprenorphine or buprenorphine/naloxone daily at a dose of at least 16mg per day for at least the prior 30 days for treatment of Opioid Use Disorder by Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria
• Scheduled for surgery at Massachusetts General Hospital where greater than 3/10 pain is expected on post-operative day 1

Exclusion Criteria:

• Participants unable to consent to the study
• Renal insufficency with a glomerular filtration rate <30ml/min (participants would be unable to use ketorolac which is a part of the multimodal anesthetic plan)
• Liver cirrhosis with a Model for End-Stage Liver Disease (MELD) score > 25 (participants would be unable to use Tylenol which is part of the multimodal anesthetic plan)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Continue Group; Those who continue taking their standard dose of buprenorphine before, during and after surgery.	Drug: Buprenorphine; Participants will be randomly assigned to be maintained on their daily dose of buprenorphine or to have their buprenorphine reduced to 16mg on the day before surgery. Participants in the reduced group will then be prescribed 8mg buprenorphine daily from the day of surgery until transitioned back to their regular dose of buprenorphine when postoperative surgical pain has subsided; Other Names: Subutex; Drug: Buprenorphine/naloxone; Participants will be randomly assigned to be maintained on their daily dose of buprenorphine/naloxone or to have their buprenorphine/naloxone reduced to 16mg on the day before surgery. Participants in the reduced group will then be prescribed 8mg buprenorphine daily from the day of surgery until transitioned back to their regular dose of buprenorphine when postoperative surgical pain has subsided; Other Names: Suboxone
Active Comparator: Reduce Group; Those who are placed on a lower dose of buprenorphine starting one day before surgery and during the time period after surgery until the pain from the surgery has decreased. Once the pain from the surgery has decreased, you will be put back on your full dose of buprenorphine.	Drug: Buprenorphine; Participants will be randomly assigned to be maintained on their daily dose of buprenorphine or to have their buprenorphine reduced to 16mg on the day before surgery. Participants in the reduced group will then be prescribed 8mg buprenorphine daily from the day of surgery until transitioned back to their regular dose of buprenorphine when postoperative surgical pain has subsided; Other Names: Subutex; Drug: Buprenorphine/naloxone; Participants will be randomly assigned to be maintained on their daily dose of buprenorphine/naloxone or to have their buprenorphine/naloxone reduced to 16mg on the day before surgery. Participants in the reduced group will then be prescribed 8mg buprenorphine daily from the day of surgery until transitioned back to their regular dose of buprenorphine when postoperative surgical pain has subsided; Other Names: Suboxone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain scores at 24 hours post-operative procedure	Average pain scores at 24 hours post-op	24 hours

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Zhang Yi, MD PhD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2020
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: September 13, 2019
• First Submitted That Met QC Criteria: September 13, 2019
• First Posted (Actual): September 16, 2019

Study Record Updates

• Last Update Posted (Actual): September 16, 2019
• Last Update Submitted That Met QC Criteria: September 13, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Narcotic-Related Disorders; Substance-Related Disorders; Disease; Opioid-Related Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine; Naloxone; Buprenorphine, Naloxone Drug Combination
• Other Study ID Numbers: 2019P001092

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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