Open-Label Noninferiority Study in the Treatment of Opioid Dependence1
THE TANUM STUDY
A CLINICAL STUDY OF EXTENDED-RELEASE NALTREXONE (XR-NTX) VS ORAL BUPRENORPHINE-NALOXONE (BUP-NX) IN OPIOID DEPENDENCE CONFIRMED NONINFERIORITY OF XR-NTX VS BUP-NX.
A 12-week, multicenter, outpatient, open-label, randomized clinical trial of opioid dependent (DSM-IV criteria) patients, age 18-60 years, in Norway.
73 individuals were excluded due to: refusal to participate (51), not meeting inclusion criteria (9), failing detoxiﬁcation (6), or other reasons (7).
The study results confirmed noninferiority of XR-NTX to BUP-NX. This was based on three primary endpoints:
- Number of days of use of heroin and other illicit opioids
- Trial completion rate
- Proportion of illicit opioid-negative urine drug tests (UDTs)
DAYS OF USE: HEROIN AND OTHER ILLICIT OPIOIDS
Treatment with XR-NTX showed noninferiority to BUP-NX in days of use of heroin and other illicit opioids
- Mean difference in days of heroin use was -3.2 (95% CI, -4.9 to -1.5; P<0.001) and mean difference in days of other illicit opioid use was -2.7 (95% CI, -4.6 to -0.9; P<0.001) when comparing XR-NTX to BUP-NX
FEWER DAYS OF USE WITH XR-NTX THAN WITH BUP-NX
Retention in the XR-NTX group was noninferior to the BUP-NX group at the conclusion of the 12-week study.
- The proportion of participants retained in the XR-NTX group (n=71) was noninferior to the BUP-NX group (n=72) (difference, -0.1; 95% CI, -0.2 to 0.1; P=0.04)
- The percentage of patients who completed the 12 weeks of treatment was 70% (n=56) in the XR-NTX group and 62% (n=49) in the BUP-NX group
RETENTION TIME ON XR-NTX WAS SIMILAR TO BUP-NX
P=0.33, log-rank test
OPIOID-NEGATIVE URINE DRUG TESTS (UDTS)
The total number of opioid-negative UDTs was noninferior when comparing XR-NTX to BUP-NX.
MEAN PERCENTAGE OF OPIOID-NEGATIVE WEEKLY UDTS
95% CI, -0.04 to 0.2; P<0.001
The study was not blinded. Participants of each treatment group knew which medication they were receiving during 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 increase risk of overdose in newly detoxified opioid users, the use of placebo and/or masking of medications was considered unethical
FULL STUDY DESIGN
232 adult 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 either receive daily oral flexible dose BUP-NX, 4 to 24 mg/d (n=79), or XR-NTX, 380 mg, administered intramuscularly every fourth week (n=80). Participants were given weekly urine drug tests (UDTs). The weekly UDTs were calculated as the number of opioid-negative urine drug screens 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 women who were pregnant or breastfeeding, or had other drug or alcohol dependence, or serious somatic or psychiatric illness that interfered with study participation.
DEMOGRAPHICS AND CLINICAL BASELINE CHARACTERISTICS
|Intention to Treat
|Age, years||36.4 (8.8)||35.7 (8.5)|
|Male||61 (76.3%)||54 (68.4%)|
|Female||19 (23.6%)||25 (31.6%)|
|White||72 (90%)||70 (88.6%)|
|Heavy opioid use, years||8.9 (7.8)||9.6 (10.5)|
|Heroin use, years||6.9 (5.8)||6.7 (5.2)|
|Other illicit opioid use, years||2.4 (5.1)||3.2 (7.0)|
|Heroin use during past 30 days||7.6 (11.0)||12.0 (12.9)|
|Other illicit opioid use during past 30 days||8.2 (11.1)||14.5 (13.2)|
Data are mean (SD) or number (%).
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.
See Important Safety Information below. Discuss all benefits and risks with your patients. See Prescribing Information and Medication Guide with your patients.