Extended-Release Naltrexone and Buprenorphine-Naloxone Equally Safe and Effective: Outcomes from CTN-0051

• Medication-assisted treatment is superior to placebo and counseling-only treatment for opioid use disorders.
• Buprenorphine-naloxone (BUP-NX) and extended-release naltrexone (XR-NTX) are two such medications, and they can be prescribed in any U.S. medical setting, making them key components of a public health response to the current opioid epidemic.
• While both medications are used to treat the same disorder, however, they are pharmacologically and conceptually distinct interventions for preventing opioid relapse, and, until now, a study directly comparing them to each other had not been done.

This NIDA Clinical Trials Network study, CTN-0051, aimed to fill that research gap by comparing opioid relapse-free survival between XR-NTX and BUP-NX. It was a 24-week, open-label, randomized controlled, comparative effectiveness trial held in 8 U.S. community-based inpatient services, with outpatient follow-up for participants, all of whom were users or heroin or prescription-type opiates.

Half of the participants (283) were randomized to receive XR-NTX (Vivitrol), a monthly injection, with the other half (287) assigned to receive BUP-NX (Suboxone), which came as a film patients placed under their tongues (“sublingual”). Participants were followed for 24 weeks of outpatient treatment.

As expected, patients randomized to XR-NTX had a substantial induction hurdle: XR-NTX can trigger severe withdrawal in patients if they have not detoxed from opioids first, and detox can be extremely difficult for opioid users (treatment with Suboxone can be started sooner, while the patient is still experiencing some withdrawal). As a result, fewer participants successfully initiated treatment with XR-NTX (72%) than with BUP-NX (94%).

Among all participants who were randomly assigned (“intention-to-treat” population, n=570), 24-week relapse events were greater for XR-NTX (65%) than for BUP-NX (57%). However, most or all of this difference (89%) was due to patients in the XR-NTX group dropping out of detox before receiving the medication.

Of the 474 participants who did successfully begin treatment, however, researchers found that:

• 24-week relapse events were similar for both XR-NTX and BUP-NX (about half of both groups relapsed). In other words, both medications were equally effective.
• Self-reported opioid craving was initially less with XR-NTX than with BUP-NX, but by week 24, participants reported similar levels of craving.
• With the exception of mild-to-moderate XR-NTX injection site reactions, treatment-emergent adverse events, including overdose, did not differ between treatment groups.

Conclusions: In this population of opioid users, it was more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications.

For more on these important outcomes, check out these national news stories about the study: 
New York Times, Washington Post, Wall Street Journal, and CNN.

Find it in the CTN Dissemination Library!