Effect of Buprenorphine/Naloxone Continuation on Pain Control and Opioid Use

• ClinicalTrials.gov Identifier: NCT03266445
• Recruitment Status: Not yet recruiting
• First Posted: August 30, 2017
• Last Update Posted: October 9, 2018
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Aurora Naa-Afoley Quaye, Massachusetts General Hospital

Study Description

Brief Summary:

The aim of this study is to determine the effect of continuation of buprenorphine/naloxone in patients with history of Opioid Use Disorder (OUD) scheduled for surgery compared to reduced dose buprenorphine/naloxone prior to surgery on pain scores, opioid consumption, depressive symptoms and severity of substance use dependence- including record of problematic use of any non-prescribed opioids, alcohol and illicit narcotics.

Condition or disease	Intervention/treatment	Phase
Opioid-use Disorder; Pain, Acute; Surgery	Drug: buprenorphine/naloxone	Phase 4

Detailed Description:

Opioid use disorder (OUD) is characterized by non-remitting cycles of remission and opioid abuse relapse. It is associated with a high rate of psychiatric and physical co-morbidity when left untreated. Buprenorphine and buprenorphine/naloxone are effective opioid maintenance therapy (OMT) for OUD, however, treatment of acute post-surgical pain in patients taking buprenorphine is perceived to be challenging. Although not substantiated in clinical studies, the combination of high receptor binding affinity, long half-life, and partial mu opioid receptor agonism with buprenorphine/naloxone are thought to inhibit the analgesic actions of full mu opioid receptor agonists, potentially making standard postoperative pain control strategies less effective. There is no evidence based standard of care for optimal acute pain management strategies for patients taking buprenorphine and most recommendations are based upon provider opinion- occasionally conflicting along specialty lines. Some providers, mainly consisting of surgeons and anesthesiologists, recommend that buprenorphine should be discontinued at least 72 hours prior to elective surgery and replaced with low dose opioid agonists, in the interim. Other providers, mainly comprising of psychiatrists, contend that these patients should be maintained on buprenorphine throughout the peri-operative period at either a full or reduced dose to prevent an indeterminate risk of substance abuse relapse that can occur as consequence to the abrupt termination buprenorphine in the highly stressful surgical period. This study aims to inform this important unresolved question in the clinical care of this growing population. The investigators seek to determine the effectiveness of managing postoperative pain in patients with OUD where buprenorphine/naloxone is continued perioperatively compared to patients where buprenorphine/naloxone is reduced to a lower dose. Longitudinally, the investigators also intend to determine if there is a difference in substance abuse relapse in patients where buprenorphine/naloxone is continued vs. held by using self assessments and communication with the participant's buprenorphine provider.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 76 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Participants will be randomly assigned to be maintained on their daily dose of buprenorphine/naloxone or to have their buprenorphine/naloxone reduced to 8mg prior to surgery. Each group will have identical perioperative treatment plans. Primary outcome measured is pain scores following surgery.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Estimated Study Start Date: October 5, 2018
• Estimated Primary Completion Date: December 31, 2021
• Estimated Study Completion Date: February 26, 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: FULL-BUPRENORPHINE; Participants will be randomly assigned to be maintained on their daily dose of buprenorphine/naloxone	Drug: buprenorphine/naloxone; The intervention will be to either continue taking buprenorphine/naloxone or to have the medication reduced perioperatively.; Other Name: Reduction vs Continuation
No Intervention: LOW-BUPRENORPHINE (control); Participants will be randomly assigned to have their daily dose of buprenorphine/naloxone reduced to 8mg on the day of surgery

Outcome Measures

Primary Outcome Measures :

1. Post-operative pain scores [ Time Frame: 24 hours after surgery ]
   Level of pain on a Visual Analog Scale of 0-100 (0=no pain; 100=worst pain imaginable) This scale will be used to quantify the varying degrees of pain or discomfort experienced by the participant.

Secondary Outcome Measures :

1. Postoperative opioid consumption [ Time Frame: 24 hours, 48 hours and 72 hours after surgery ]
   Amount of opioids needed for pain control postoperatively
2. Post-operative pain scores [ Time Frame: 48 hours, 72 hours after surgery ]
   Level of pain on Visual Analog Scale 0-100 (0= no pain 100= worst pain imaginable) We will compare the results of the 48 and 72 hour time-points with the 24 hour time-point.
3. Presence, severity of substance abuse [ Time Frame: 1 month after surgery ]
   Participants will complete questionnaires to identify the presence and severity of substance abuse.These values will be compared with baseline values obtained preoperatively.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• currently taking buprenorphine or buprenorphine/naloxone daily for treatment of opioid use disorder by DSM-V criteria
• on buprenorphine or buprenorphine/naloxone dose of greater than 8mg for at least 30 days
• ASA health class I-III

Exclusion Criteria:

• Unable to consent to the study
• Significant pulmonary or cardiac disease
• Renal insufficiency with a glomerular filtration rate less than 30ml/min
• Liver cirrhosis with a Model for End-Stage Liver Disease (MELD) score of greater than 25

Contacts and Locations

Contacts

Contact: Aurora Quaye, MD; 617-726-2000; aquaye@partners.org

Sponsors and Collaborators

Massachusetts General Hospital

Investigators

• Principal Investigator: Aurora Quaye, MD; Massachusetts General Hospital

More Information

Additional Information:

Center for Behavioral Health Statistics and Quality. Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health. 2015. HHS Publication No. SMA 15-4927, NSDUH Series H-50. 

Publications:

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Schuckit MA. Treatment of Opioid-Use Disorders. N Engl J Med. 2016 Jul 28;375(4):357-68. doi: 10.1056/NEJMra1604339. Review.

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Wilkinson KM, Krige A, Brearley SG, Lane S, Scott M, Gordon AC, Carlson GL. Thoracic Epidural analgesia versus Rectus Sheath Catheters for open midline incisions in major abdominal surgery within an enhanced recovery programme (TERSC): study protocol for a randomised controlled trial. Trials. 2014 Oct 21;15:400. doi: 10.1186/1745-6215-15-400.

• Responsible Party: Aurora Naa-Afoley Quaye, Instructor M.D., Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT03266445
• Other Study ID Numbers: 2017P001425
• First Posted: August 30, 2017
• Last Update Posted: October 9, 2018
• Last Verified: October 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: IPD will only be available to researchers involved in the study. All data will be collected and stored securely using the Redcap system to preserve privacy and confidentiality. Information regarding substance abuse history, including illicit narcotic use, will remain confidential and personal identifiers will be removed during data storage. Only members of the research team will have access to the data that participants have consented to provide. Participants will be informed that they have the right to not answer any question that makes them feel uncomfortable.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Aurora Naa-Afoley Quaye, Massachusetts General Hospital:

relapse; buprenorphine/naloxone; opioids; narcotics; post-surgical pain

Additional relevant MeSH terms:

Acute Pain; Opioid-Related Disorders; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Pain; Neurologic Manifestations; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Naloxone; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Narcotic Antagonists