Standard Versus High Dose ED-Initiated Buprenorphine Induction

Phase 3

Recruiting

• Conditions: Opioid Use Disorder
• Interventions: Drug: Buprenorphine

• Registration Number: NCT06494904
• Lead Sponsor: Yale University

Brief Summary

This study is a multisite double-blind, double-dummy, randomized clinical trial enrolling ED patients with untreated moderate to severe opioid use disorder (OUD) to compare Standard Dose Induction (SDI) and High Dose Induction (HDI) on rates of participation in OUD treatment within 10 days post randomization, and opioid withdrawal symptoms, opioid craving, and use of illicit and non-prescribed drugs.

Detailed Description

This study will recruit, train, and provide resources to approximately 4 ED systems throughout the U.S. to recruit ED patients presenting with OUD not receiving medications for opioid use disorder (MOUD) as part of an RCT to compare SDI (Zubsolv 5.7/1.4 mg buprenorphine/naloxone\* plus 2 placebo tablets) with HDI (three Zubsolv 5.7/1.4 mg\* buprenorphine/naloxone tablets) to evaluate rate of participation in OUD treatment within 10 days post-randomization and differences in outcomes of tolerability, opioid withdrawal symptoms, craving, and use of illicit drugs.

Study Timeline

• Study First Submitted: 2024-07-02
• Study First Submitted QC: 2024-07-02
• Study First Posted: 2024-07-10
• Study Start: 2024-12-06
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-23
• Last Update Posted: 2025-04-25
• Primary Completion: 2027-04
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 360

Inclusion Criteria

All patients enrolled into the study must:

1. Be 18-65 years of age.
2. Be treated in the ED during study screening hours.
3. Meet DSM-5 diagnostic criteria for moderate to severe OUD.
4. Have a Clinical Opiate Withdrawal Scale (COWS) score of ≥8 at enrollment (including 2 objective signs of withdrawal at enrollment).
5. Have a urine toxicology test that is positive for opioids.
6. Be able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study.

Exclusion Criteria

All patients enrolled into the study must not:

1. Have a medical or psychiatric condition that requires hospitalization at the time of index ED visit.
2. Have a known hypersensitivity reaction to buprenorphine/naloxone
3. Be actively suicidal or severely cognitively impaired precluding informed consent.
4. Require ongoing prescription for opioid analgesics.
5. Have a physical exam or reported history consistent with severe liver failure
6. Have a positive urine test for methadone and reported use in the past 72 hours
7. Be a prisoner or in police custody at the time of index ED visit.
8. Be unwilling to follow study procedures (e.g., unwilling to provide permission to contact referral provider/program or unavailable for the follow-up assessments)
9. Have prior enrollment in the current study.
10. Receiving MOUD treatment within the past 7 days.
11. Be pregnant as determined by human gonadotropin (hCG) testing at the index ED visit
12. Have a respiratory rate <8 or oxygen saturation <93%
13. Be a participant in any other clinical trial in which medications are being delivered or the use of an investigational drug or device within the last 30 days

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard SL-BUP	Buprenorphine	Participants will receive three pills; one 5.7 mg Zubsolv pill with active medication and two placebo pills.
High Dose SL-BUP	Buprenorphine	Participants will receive three 5.7 mg Zubsolv pills; all will be active medication.

Primary Outcome Measures

Name	Time	Method
Engagement in Treatment (10)	Within 10 days after study randomization	The proportion of patients in each of the two study arms participating in OUD treatment within 10 days after the study randomization

Secondary Outcome Measures

Name	Time	Method
Craving	Measured daily for 10 days post randomization	The maximum intensity of opioid cravings during the preceding 24 hours assessed daily for 10 days post randomization using a numerical rating scale (0 to 10).
Substance Use	Measured daily for 10 days post randomization	The number of days with illicit opioid and other substance use based on self-reported data obtained daily during the first 10 days post randomization
Withdrawal	Measured daily for 10 days post randomization	The maximum intensity of opioid withdrawal symptoms during the preceding 24 hours assessed daily for 10 days post randomization using a numerical rating scale (0 to 10).
Engagement in Treatment (30)	Within 30 days after randomization	The proportion of patients in each of the two study arms participating in OUD treatment

Trial Locations

Locations (5)

Highland Hospital; 🇺🇸 Oakland, California, United States

San Leandro Hospital; 🇺🇸 San Leandro, California, United States

Maine Medical Center; 🇺🇸 Portland, Maine, United States

Cooper University Hospital; 🇺🇸 Camden, New Jersey, United States

University of Utah Hospital; 🇺🇸 Salt Lake City, Utah, United States