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

Drug Alcohol Depend. 2018 Jun 1;187:171-178. doi: 10.1016/j.drugalcdep.2018.02.023. Epub 2018 Apr 10.

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.

Keywords: Detoxification; Naltrexone; Opioid receptor antagonist; Opioid use disorder; Opioid withdrawal; Opioids.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Ambulatory Care / methods*
  • Ambulatory Care / 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*
  • Opioid-Related Disorders / epidemiology
  • Opioid-Related Disorders / psychology
  • Outpatients / psychology
  • Patient Transfer / methods*
  • Patient Transfer / trends
  • Substance Withdrawal Syndrome / drug therapy
  • Substance Withdrawal Syndrome / epidemiology
  • Substance Withdrawal Syndrome / psychology

Substances

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