An open-label noninferiority study of extended-release naltrexone (XR-NTX) and buprenorphine-naloxone (BUR-NX) was conducted in the treatment of opioid dependence1
TANUM: AN OPEN-LABEL,
HEAD-TO-HEAD RANDOMIZED CLINICAL NONINFERIORITY TRIAL1
Extended-release naltrexone (XR-NTX) was found to be noninferior to buprenorphine-naloxone (BUP-NX)
A Norway-based, 12-week, open-label, randomized clinical trial in which patients recruited from outpatient addiction clinics and detoxification units were randomized to oral BUP-NX (n=79) or XR-NTX (n=80) after detoxification. Participants were asked to attend standard drug counseling, but no behavioral interventions could be initiated*
- Participants were recruited from outpatient addiction clinics and detoxification units
- 159 participants were randomized after detoxification
- Participants were asked to attend standard drug counseling, but no behavioral interventions could be initiated
- Primary endpoints were number of days of use of heroin and other illicit opioids; trial completion rate; and proportion of opioid-negative urine drug tests (UDTs)
The study was not blinded. Participants in each treatment group knew which medication they were receiving during the trial.
- For the study to have been blinded, it would have required placebo injections like the XR-NTX kits or placebo tablets for BUP-NX
- Patients would be able to determine their respective treatment quite quickly, given their long experience with opioid use
- Due to an increased risk of overdose in newly detoxified opioid users, the use of placebo and the masking of medications were considered unethical
Days of use of heroin and other illicit opioids for XR-NTX vs BUP-NX
- Patients who received XR-NTX used heroin, on average, 3.2 days less (95% CI, -4.9 to -1.5; P<0.001) and other illicit opioids, on average, 2.7 days less (95% CI, -4.6 to -0.9; P<0.001) than patients who received BUP-NX
RETENTION TIME ON XR-NTX VS BUP-NX AT THE CONCLUSION OF THE 12-WEEK STUDY
P=0.33, log-rank test
TOTAL NUMBER OF OPIOID-NEGATIVE UDTs FOR XR-NTX VS BUP-NX
Mean (SD), 0.9 (0.3) and 0.8 (0.4), respectively; mean difference, 0.1 with 95% CI, -0.04 to 0.2; P<0.001.
Funding/Support: The study was supported by unrestricted grants from the Research Council of Norway and the Western Norway Regional Health Authority. Financial support was also received from the Norwegian Centre for Addiction Research, University of Oslo, and from Akershus University Hospital.
Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication; however, Alkermes, Inc. was allowed to comment on the manuscript before submission for publication.
*Clinical trial of opioid-dependent (DSM-IV criteria) patients, age 18-60 years. 232 opioid-dependent individuals were recruited from outpatient addiction clinics and detoxification units. After screening and inclusion, participants were referred to a detoxification unit, and randomized to treatment after detoxification. 159 participants were randomized to receive either daily, oral, flexible-dose BUP-NX 4 to 24 mg/day (n=79), or XR-NTX 380 mg, administered intramuscularly every fourth week (n=80). Participants were given weekly urine drug tests (UDTs). Proportion of opioid-negative UDTs were calculated as the number of opioid-negative UDTs divided by the total number of attended tests. Missing UDTs were considered as testing positive for opioids in all participants. Participants were asked to attend standard drug counseling, but no behavioral interventions could be initiated. Exclusion criteria included pregnancy or breastfeeding; other drug or alcohol dependence, or serious somatic or psychiatric illness interfering with study participation.
VIVITROL is not right for everyone. There are significant risks from VIVITROL treatment, including risk of opioid overdose, injection site reactions and sudden opioid withdrawal.
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