Outpatient transition to extended-release injectable naltrexone for patients with opioid use disorder: A phase 3 randomized trial.

Abstract

BACKGROUND:

Injectable extended-release naltrexone (XR-NTX), approved to prevent relapse to opioid dependence, requires initial abstinence. This multisite outpatient clinical trial examined the efficacy and safety of low-dose oral naltrexone (NTX), combined with a brief buprenorphine (BUP) taper and standing ancillary medications, for detoxification and induction onto XR-NTX.

METHODS:

Patients (N = 378) were randomized, stratified by primary short-acting opioid-of-use, to one of three regimens: NTX + BUP; NTX + placebo BUP (PBO-B); placebo NTX (PBO-N) + PBO-B. Patients received 7 days of ascending NTX or placebo, concurrent with a 3-day BUP or placebo taper, and ancillary medications in an outpatient setting. Daily psychoeducational counseling was provided. On Day 8, patients passing a naloxone challenge received XR-NTX.

RESULTS:

Rates of transition to XR-NTX were comparable across groups: NTX/BUP (46.0%) vs. NTX/PBO-B (40.5%) vs. PBO-N/PBO-B (46.0%). Thus, the study did not meet its primary endpoint. Adverse events, reported by 32.5% of all patients, were mild to moderate in severity and consistent with opioid withdrawal. A first, second, and third XR-NTX injection was received by 44.4%, 29.9%, and 22.5% of patients, respectively. Compared with the PBO-N/PBO-B group, the NTX/BUP group demonstrated higher opioid abstinence during the transition and lower post-XR-NTX subjective opioid withdrawal scores.

CONCLUSIONS:

A 7-day detoxification protocol with NTX alone or NTX + BUP provided similar rates of induction to XR-NTX as placebo. For those inducted onto XR-NTX, management of opioid withdrawal symptoms prior to induction was achieved in a structured outpatient setting using a well-tolerated, fixed-dose ancillary medication regimen common to all three groups.

• Authors: Adam Bisaga, Paolo Mannelli, Miao Yu, Narinder Nangia, Christine E Graham, D Andrew Tompkins, Thomas R Kosten, Sarah C Akerman, Bernard L Silverman, Maria A Sullivan
• Journal: Drug and alcohol dependence (Drug Alcohol Depend) Vol. 187 Pg. 171-178 (06 01 2018) ISSN: 1879-0046 [Electronic] Ireland
• PMID: 29674251 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Delayed-Action Preparations
• Narcotic Antagonists
• Buprenorphine
• Naltrexone

Topics

• Adult
• Ambulatory Care (methods, trends)
• Buprenorphine (administration & dosage)
• Delayed-Action Preparations (administration & dosage)
• Double-Blind Method
• Female
• Humans
• Injections, Intramuscular
• Male
• Middle Aged
• Naltrexone (administration & dosage)
• Narcotic Antagonists (administration & dosage)
• Opioid-Related Disorders (drug therapy, epidemiology, psychology)
• Outpatients (psychology)
• Patient Transfer (methods, trends)
• Substance Withdrawal Syndrome (drug therapy, epidemiology, psychology)