Comparative effectiveness of extended-release naltrexone vs buprenorphine-naloxone for opioid relapse prevention1
X:BOT: A MULTICENTER, OPEN-LABEL, RANDOMIZED CONTROLLED TRIAL
x:bot study design1
A US-based, 24-week, multicenter, open-label, randomized clinical trial of opioid use disorder (DSM-5 criteria) outpatients aged ≥18 years
- 772 participants were recruited and screened during voluntary, usual care, inpatient detoxification admissions
- Participants had used non-prescribed opioids in the previous 30 days
570 participants were randomized to receive either daily sublingual self-administered BUP-NX 8 to 24 mg/d (n=287), or XR-NTX 380 mg, prepared and administered by an HCP intramuscularly every fourth week (n=283)
- XR-NTX treatment could be initiated and administered by an HCP after complete detoxification (≥3 days from last opioid use), opioid-negative urine drug test (UDT), and a negative naloxone challenge. Criteria were not met by 79 participants
- BUP-NX treatment could be initiated once withdrawal symptoms emerged. Criteria were not met by 17 participants
- Exclusion criteria included the presence of serious medical, psychiatric, or substance use disorders; liver function tests >5x the upper limit of normal; those who were suicidal or homicidal; had allergy or sensitivity to XR-NTX or BUP-NX; were not able to have safe intramuscular XR-NTX treatment; had methadone maintenance; had chronic pain requiring opioids; had a legal status precluding study completion; or women who were or could become pregnant or were breastfeeding
- The study design, particularly the acute detoxification setting, flexible randomization, and varied induction protocols, limits interpretation and generalizability
- Site differences in detoxification protocols and lengths of stay contributed to induction and relapse events, and showed substantial variability in standard opioid detoxification approaches. Ease of induction is a well-known limitation of XR-NTX
- An open-label, real-world effectiveness study such as this includes more sources of bias than a tightly controlled efficacy study, including the absence of placebo control or masking
- The intention-to-treat (ITT) population included all randomized participants
- The per-protocol population included only the participants who successfully began study medication
Participants who were randomized but unable to initiate treatment were considered induction failures and excluded from the per-protocol population.
Demographics and baseline clinical characteristics1
|Age (years)||34.0 (9.5)||33.7 (9.8)||33.7 (9.3)||33.7 (9.8)|
|Male||195 (69%)||206 (72%)||138 (68%)||193 (71%)|
|White||206 (73%)||215 (75%)||157 (77%)||201 (74%)|
|Duration of opioid use (years)||12.8 (9.0)||12.2 (9.0)||12.9 (9.1)||12.3 (9.1)|
|Primary opioid used in the 7 days
before detoxification admission
|Buprenorphine||6 (2%)||2 (1%)||4 (2%)||2 (1%)|
|Opioid analgesics||43 (15%)||47 (16%)||36 (18%)||45 (17%)|
|Methadone||3 (1%)||4 (1%)||3 (1%)||4 (1%)|
|Heroin||230 (81%)||233 (81%)||160 (78%)||218 (81%)|
PRIMARY Outcome measure1
Primary outcome measure was time to a relapse event
- Relapse was defined as opioid use after Day 20 postrandomization: either 4 consecutive weeks with at least 1 day of non-study opioid use as measured by a weekly UDT or 7 consecutive days with self-reported opioid use
Primary endpoint: relapse rates1
The ITT population included all randomized participants. The per-protocol population included only the participants who successfully began study medication.
Opioid relapse rates, Weeks 3-24, ITT1
Opioid relapse rates, Weeks 3-24, per protocol1
SECONDARY ENDPOINT: OPIOID CRAVING SCORE IN PATIENTS ADMINISTERED XR-NTX VS BUP-NX OVER 24 WEEKS1
Craving was self-reported with an opioid-craving VAS, range 0-100.
|Treatment-emergent adverse events||
XR-NTX 380 mg
|Participants with one or more treatment-emergent adverse event‡||111 (54%)||141 (52%)|
|Number of treatment-emergent adverse events||247||334|
|Study medication discontinued due to adverse event||6||8|
|Type of treatment-emergent adverse event|
|Injection site reaction, mild or moderate||46||N/A|
|Injury, poisoning, and procedural complications||23||25|
|Infections and infestations||22||27|
|Nervous system disorders||22||28|
|Participants with one or more overdose event (all)||15||8|
|Participants with one or more overdose event (per protocol)||9||7|
|Number of overdose events (all)||18||10|
|Number of overdose events (per protocol)||10||9|
|Fatal overdose events|
|Number of fatal overdose events (all)||2||3|
|Number of fatal overdose events (per protocol)||2||3|
The proportion of participants reporting adverse events and serious adverse events did not differ between groups, with the exception of injection site reactions among the XR-NTX group that were of mild to moderate severity
- 2 participants treated with XR-NTX and 3 participants treated with BUP-NX had fatal overdoses
Funding: National Institute on Drug Abuse (NIDA) Clinical Trials Network.
XR-NTX was approved based on DSM-IV-TR criteria.
View the open-label, head-to-head study in the treatment of opioid dependence.
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Reference: 1. Lee JD, Nunes EV Jr, Novo P, et al. Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial. Lancet. 2018;391(10118):309-318.
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