X:bot study
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
STUDY LIMITATIONS1
- 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
POPULATIONS:
- 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
| itt population |
per-protocol population |
|||
|---|---|---|---|---|
|
XR-NTX (n=283) |
BUP-NX (n=287) |
XR-NTX (n=204) |
BUP-NX (n=270) |
|
| 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.
Adverse events1
| Treatment-emergent adverse events |
XR-NTX 380 mg (n=283) |
BUP-NX (n=287) |
|---|---|---|
| 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 |
| Gastrointestinal | 34 | 59 |
| Psychiatric disorders | 30 | 29 |
| Injury, poisoning, and procedural complications | 23 | 25 |
| Infections and infestations | 22 | 27 |
| Nervous system disorders | 22 | 28 |
| Overdose events | ||
| 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
Disclosure:
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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LEARN MOREReference: 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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