An open-label, randomized trial compared the effectiveness and safety of extended-release naltrexone (XR-NTX) vs buprenorphine-naloxone (BUP-NX)*
X:BOT: OPEN-LABEL, HEAD-TO-HEAD STUDY IN THE TREATMENT OF OPIOID DEPENDENCE1
- XR-NTX treatment could be initiated after complete opioid detoxification,† whereas BUP-NX could be initiated when withdrawal symptoms emerged. 79 participants could not be initiated on XR-NTX due to unsuccessful opioid detoxification and 17 participants could not be initiated onto BUP-NX
- The primary outcome was the time to a relapse event.‡ Published secondary outcomes included opioid craving,§ proportion of participants successfully initiated onto study medication, safety, and frequency of non-study opioid use
Study Limitations
- 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
Primary endpoint
The intention-to-treat (ITT) population included all randomized participants. The per-protocol population included only the participants who successfully began study medication
OPIOID RELAPSE, WEEKS 3-24 – ITT
OR 1.44, 95% CI 1.02-2.01; P=0.036
OPIOID RELAPSE, WEEKS 3-24 – PER-PROTOCOL
OR 0.87, 95% CI 0.60-1.25; P=0.44
In the per-protocol population, median time to relapse was similar, rates of study completion were similar.Secondary endpoint
VAS=visual analogue scale
ADVERSE REACTIONS IN THE X:BOT OPEN-LABEL, HEAD-TO-HEAD STUDY1
ADVERSE EVENTS
| Treatment-emergent adverse events | XR-NTX 380 mg (n=283) | BUP-NX (n=287) |
||
| Participants with one or more treatment-emergent adverse eventII | 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 minor to moderate severity
¶ P=0.14 (Fisher’s exact).
# P=0.31 (Fisher’s exact).
**Four participants reported more than one overdose event. Three of the four participants were randomly assigned to XR-NTX (two of these induction failures, one successfully inducted); each reported two overdose events. One of the four was randomly assigned to BUP-NX (successfully inducted) and reported three overdose events. None of these nine overdoses were fatal.
This is not a complete list of adverse events for VIVITROL. Please see Important Safety Information and full Prescribing Information for additional safety information.
DISCLOSURE
Funding: National Institute on Drug Abuse (NIDA) Clinical Trials Network.
XR-NTX was approved based on DSM-IV-TR criteria.
FULL STUDY DESIGN: X:BOT1
X:BOT was a US-based 24-week, multicenter, open-label, randomized clinical trial of opioid use disorder (DSM-5 criteria) outpatients, age 18 and above. 772 participants were recruited and screened during voluntary, usual care, inpatient detoxification admissions. Participants had used non-prescribed opioids in the previous 30 days. Of these, 570 participants were randomized to receive either daily sublingual self-administered BUP-NX, 8 to 24 mg/day (n=287), or XR-NTX, 380 mg, administered intramuscularly every fourth week (n=283). XR-NTX treatment could be initiated after ≥3 days from last opioid use, opioid-negative urine drug test, 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 greater than 5 times the upper limit of normal; suicidal or homicidal; had allergy or sensitivity to XR-NTX or BUP-NX; were not able to have safe intramuscular XR-NTX treatment; or women who were or could become pregnant, or were breastfeeding.
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View the open-label, head-to-head study in the treatment of opioid dependence.
DOWNLOAD X:BOT STUDYDEMOGRAPHICS and CLINICAL BASELINE CHARACTERISTICS
| Intention to Treat (N=570) |
||
|---|---|---|
| Extended-release Naltrexone (n=283) |
Buprenorphine-Naloxone (n=287) |
|
| Age, years | 34.0 (9.5) | 33.7 (9.8) |
| Male | 69% | 72% |
| Female | 31% | 28% |
| White | 73% | 75% |
| Opioid use, years | 12.8 (9.0) | 12.2 (9.0) |
| Opioid used in the 7 days before detox admission | ||
| Heroin | 81% | 81% |
| Opioid analgesic | 15% | 16% |
| Buprenorphine | 2% | 1% |
| Methodone | 1% | 1% |
Data are mean (SD).
*Clinical trial of opioid use disorder (DSM-5 criteria) outpatients, age above 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. Of these, 570 participants were randomized to receive either daily sublingual self-administered BUP-NX, 8 to 24 mg/day (n=287), or XR-NTX, 380 mg, administered intramuscularly every fourth week (n=283). XR-NTX treatment could be initiated after ≥3 days from last opioid use, opioid-negative urine drug test, and a negative naloxone challenge. BUP-NX treatment could be initiated once withdrawal symptoms emerged. Exclusion criteria included the presence of serious medical, psychiatric, or substance use disorders; liver function tests greater than 5 times the upper limit of normal; suicidal or homicidal; had allergy or sensitivity to XR-NTX or BUP-NX; were not able to have safe intramuscular XR-NTX treatment; or women who were or could become pregnant, or were breastfeeding.
†Before XR-NTX induction, participants had to complete opioid detoxification (≥3 days from last opioid use), have opioid-negative urine, and a negative naloxone challenge (no or minimal opioid withdrawal symptoms following intramuscular, subcutaneous, or intravenous administration of ≥0.4 mg dose of naloxone, a short-acting opioid antagonist).
‡Relapse was defined as opioid use after day 20, either 4 consecutive weeks with at least one day of non-study opioid as measured by a weekly urine drug test (UDT) or 7 consecutive days with self-reported opioid use.
§Craving was self-reported with an opioid-craving visual analogue scale (VAS), range 0-100.
IITreatment-emergent is defined as any adverse events that occurred after induction day in those participants inducted onto study medication. Data are n (%) or N.
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.
