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Clinical Trial
. 2024 Jul 1;7(7):e2420702.
doi: 10.1001/jamanetworkopen.2024.20702.

Extended-Release 7-Day Injectable Buprenorphine for Patients With Minimal to Mild Opioid Withdrawal

Gail D'Onofrio  1   2   3 , Andrew A Herring  4   5   6 , Jeanmarie Perrone  7 , Kathryn Hawk  1   3 , Elizabeth A Samuels  8   9 , Ethan Cowan  10 , Erik Anderson  4   5 , Ryan McCormack  11 , Kristen Huntley  12 , Patricia Owens  1 , Shara Martel  1 , Mark Schactman  13 , Michele R Lofwall  14   15 , Sharon L Walsh  14   15 , James Dziura  1 , David A Fiellin  1   2   16
Affiliations
Clinical Trial

Extended-Release 7-Day Injectable Buprenorphine for Patients With Minimal to Mild Opioid Withdrawal

Gail D'Onofrio et al. JAMA Netw Open. .

Abstract

Importance: Buprenorphine is an effective yet underused treatment for opioid use disorder (OUD).

Objective: To evaluate the feasibility (acceptability, tolerability, and safety) of 7-day injectable extended-release buprenorphine in patients with minimal to mild opioid withdrawal.

Design, setting, and participants: This nonrandomized trial comprising 4 emergency departments in the Northeast, mid-Atlantic, and Pacific geographic areas of the US included adults aged 18 years or older with moderate to severe OUD and Clinical Opiate Withdrawal Scale (COWS) scores less than 8 (minimal to mild), in which scores range from 0 to 7, with higher scores indicating increasing withdrawal. Exclusion criteria included methadone-positive urine, pregnancy, overdose, or required admission. Outcomes were assessed at baseline, daily for 7 days by telephone surveys, and in person at 7 days. Patient recruitment occurred between July 13, 2020, and May 25, 2023.

Intervention: Injection of a 24-mg dose of a weekly extended-release formulation of buprenorphine (CAM2038) and referral for ongoing OUD care.

Main outcomes and measures: Primary feasibility outcomes included the number of patients who (1) experienced a 5-point or greater increase in the COWS score or (2) transitioned to moderate or greater withdrawal (COWS score ≥13) within 4 hours of extended-release buprenorphine or (3) experienced precipitated withdrawal within 1 hour of extended-release buprenorphine. Secondary outcomes included injection pain, satisfaction, craving, use of nonprescribed opioids, adverse events, and engagement in OUD treatment.

Results: A total of 100 adult patients were enrolled (mean [SD] age, 36.5 [8.7] years; 72% male). Among the patients, 10 (10.0% [95% CI, 4.9%-17.6%]) experienced a 5-point or greater increase in COWS and 7 (7.0% [95% CI, 2.9%-13.9%]) transitioned to moderate or greater withdrawal within 4 hours, and 2 (2.0% [95% CI, 0.2%-7.0%]) experienced precipitated withdrawal within 1 hour of extended-release buprenorphine. A total of 7 patients (7.0% [95% CI, 2.9%-13.9%]) experienced precipitated withdrawal within 4 hours of extended-release buprenorphine, which included 2 of 63 (3.2%) with a COWS score of 4 to 7 and 5 of 37 (13.5%) with a COWS score of 0 to 3. Site pain scores (based on a total pain score of 10, in which 0 indicated no pain and 10 was the worst possible pain) after injection were low immediately (median, 2.0; range, 0-10.0) and after 4 hours (median, 0; range, 0-10.0). On any given day among those who responded, between 29 (33%) and 31 (43%) patients reported no cravings and between 59 (78%) and 75 (85%) reported no use of opioids; 57 patients (60%) reported no days of opioid use. Improving privacy (62%) and not requiring daily medication (67%) were deemed extremely important. Seventy-three patients (73%) were engaged in OUD treatment on day 7. Five serious adverse events occurred that required hospitalization, of which 2 were associated with medication.

Conclusions and relevance: This nonrandomized trial of the feasibility of a 7-day buprenorphine injectable in patients with minimal to mild opioid withdrawal (COWS scores, 0-7) found the formulation to be acceptable, well tolerated, and safe in those with COWS scores of 4 to 7. This new medication formulation could substantially increase the number of patients with OUD receiving buprenorphine.

Trial registration: ClinicalTrials.gov Identifier: NCT04225598.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Hawk reported receiving a grant from the Foundation for Opioid Response Efforts (FORE). Dr McCormack reported receiving grants from the FORE, the Emergency Medicine Foundation, and the National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH) outside the submitted work. Dr Lofwall reported receiving personal fees as a research consultant from Braeburn Pharmaceuticals, Berkshire Biomedical, Titan, and Journey Colab outside the submitted work. Dr Walsh reported receiving personal fees from Opiant Pharmaceuticals, Cervel Therapeutics, Lundbeck, AstraZeneca, Pocket Naloxone, Kinoxis, Braeburn Pharmaceuticals, and Titan outside the submitted work and having a patent for Tradipitant issued by the University of Kentucky and Vanda Pharmaceuticals. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Participant Flow Diagram
COWS indicates Clinical Opiate Withdrawal Scale; DSM-5, Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition); ED, emergency department; OUD, opioid use disorder. aParticipants may not have met the inclusion criteria for more than 1 reason.
Figure 2.
Figure 2.. Change in Clinical Opiate Withdrawal Scale (COWS) Scores Over Time
Each line represents 1 patient. Dashed lines represent a patient with only a screening COWS score available who experienced symptoms of precipitated withdrawal 165 minutes after injection. COWS scores ranged from 0 to 27, with higher scores indicating increasing withdrawal.
See this image and copyright information in PMC

References

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    1. National Academies of Sciences, Engineering, and Medicine . Medications for Opioid Use Disorder Save Lives. National Academies Press; 2019. - PubMed
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