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.
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. Strongly consider prescribing naloxone for the emergency treatment of opioid overdose. See Important Safety Information below. See Prescribing Information. Review Medication Guide with your patients.
REQUEST A
REPRESENTATIVE
Request a visit from a VIVITROL representative to learn more about how VIVITROL may help your appropriate patients with opioid dependence or alcohol dependence.
REQUEST A REPRESENTATIVELEARN ABOUT THE VIVITROL®
CO-PAY SAVINGS PROGRAM
Learn how the VIVITROL® Co-pay Savings Program may assist eligible§ patients with out-of-pocket expenses for their VIVITROL prescriptions.
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.
§Terms and Conditions
Eligibility for Alkermes-Sponsored Co-pay Savings. This offer is only available to patients 18 years or older, with a prescription consistent with the Prescribing Information and the patient is not enrolled in, or covered by, any local, state, federal or other government program that pays for any portion of medication costs, including but not limited to Medicare, including Medicare Part D or Medicare Advantage plans; Medicaid, including Medicaid Managed Care and Alternative Benefit Plans under the Affordable Care Act; Medigap; VA; DOD; TRICARE; or a residential correctional program.
Additional Terms of Use: This offer is not conditioned on any past, present, or future purchase, including refills. Alkermes reserves the right to rescind, revoke, or amend this offer, program eligibility, and requirements at any time without notice. This offer is limited to one per patient, may not be used with any other offer, is not transferable and may not be sold, purchased or traded, or offered for sale, purchase or trade. Void where prohibited by law. Program Administrator or its designee will have the right upon reasonable prior written notice, during normal business hours, and subject to applicable law, to audit compliance with this program.