Opioid Use DisorderPhase 4COPILOTNCT07469501
Comparing Outpatient Treatment Retention Among Individuals Using Fentanyl Randomized to Low-dose and Direct-to-inject Buprenorphine Initiation
A Phase 4 study testing Injectable buprenorphine and Sublingual Buprenorphine (SUBOXONE, Zubsolv, or generic tablets) in people with Opioid Use Disorder and Fentanyl, run by University of California, San Francisco at 1 site in United States.
Trial summary
The goal of this pragmatic randomized controlled trial is to compare treatment outcomes of two strategies for initiating buprenorphine treatment (low-dose initiation and direct-to-inject) in adults with opioid use disorder (OUD) who use fentanyl. This study aims to: 1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Opioid Use Disorder, Fentanyl
- What is being tested?
- Injectable buprenorphine and Sublingual Buprenorphine (SUBOXONE, Zubsolv, or generic tablets)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2026to May 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years of age at Visit 1.
- Documentation of an OUD diagnosis as evidenced by meeting two or more of the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) Criteria for Opioid Use Disorder
- Self-reported daily use of fentanyl ≥ 5 out of the past 7 days at baseline,
- Fentanyl-positive urine drug screening at baseline,
- Interest in stopping or reducing fentanyl use,
- Publicly insured through San Francisco Medicaid or Medicare and therefore able receive buprenorphine prescription dispensing through Community Behavioral Health Services (CBHS) Pharmacy
Who cannot join
- Currently nursing, pregnant, or anticipating pregnancy in the next 6 months
- Methadone-positive urine drug screening at baseline
- Buprenorphine-positive urine drug screening at baseline
- Be unable to provide any locator or contact information at least one contact in addition to themselves
- Any pending legal action that could prevent participation in study activities
- Presence of a condition or abnormality that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data (e.g., acute psychosis), or cognitive impairment (e.g., dementia)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
San Francisco Outpatient Buprenorphine Induction Clinic
San Francisco, California, 94103
Tricia Wright, MD, 628-754-9201, Tricia.Wright@ucsf.edu
About this study
Official title: Improving Buprenorphine Initiation Among Individuals With Opioid Use Disorder Using Fentanyl
The goal of this pragmatic randomized controlled trial is to compare treatment outcomes of two strategies for initiating buprenorphine treatment (low-dose initiation and direct-to-inject) in adults with opioid use disorder (OUD) who use fentanyl. This study aims to:
- Compare effectiveness of each strategy on treatment retention in a real world, clinical setting, and
- Assess differences between strategies in patient-reported outcomes, including withdrawal symptoms, cravings, drug use, treatment satisfaction, and overall acceptability.
Read more
Participants will:
- Be randomized to initiate buprenorphine via a low-dose initiation or direct-to-inject protocol at an outpatient buprenorphine clinic,
- Keep a diary of craving and withdrawal symptoms for the first 7 days after initiation, and
- Visit the outpatient clinic 7, 30, and 90 days after initiation for urinary drug screen and follow-up surveys.
- Conditions
- Opioid Use Disorder, Fentanyl
- Being tested
- Injectable buprenorphine, Sublingual Buprenorphine (SUBOXONE, Zubsolv, or generic tablets)
- Keywords
- Buprenorphine initiation, Low-dose initiation, Direct-to-inject initiation, Medication for opioid use disorder, Outpatient treatment for opioid use disorder
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Injectable buprenorphineDrug
Also called Direct-to-inject, Brixadi, Sublocade, Long-acting injectable buprenorphine
Starting dose (8-32mg) of long-acting injectable buprenorphine (Brixadi or Sublocade) on day 1, followed by monthly maintenance doses (e.g., 128mg Brixadi or 300mg Sublocade)
Sublingual Buprenorphine (SUBOXONE, Zubsolv, or generic tablets)Drug
Also called Low-dose buprenorphine initiation, Suboxone, Buprenorphine blister packs
Starting dose (0.5mg) of sublingual buprenorphine tablets in blister packs (Brixadi or Sublocade) on day 1, followed by 0.5-1.0mg daily increases in week 1 and maintenance dosing based on shared decision-making with provider
| Study group | Role | What they receive |
|---|---|---|
| Low-dose initiation (LDI) | Active comparator | Participants start 0.5mg sublingual buprenorphine (Subutex) and gradually increase by 0.5-1.0mg daily for 7 days Receives: Drug: Sublingual Buprenorphine (SUBOXONE, Zubsolv, or generic tablets) |
| Direct-to-inject (DTI) | Experimental | Participants receive 8-32mg long-acting injectable buprenorphine (Brixadi or Sublocade) on day 1, followed by monthly injections as discussed with the provider Receives: Drug: Injectable buprenorphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Continuous retention in outpatient buprenorphine treatment by day 90
Receiving continuous treatment with buprenorphine sublingual prescriptions or injections administrations during the 90 days of follow up post-randomization as intended-to-treat. A period without buprenorphine treatment ≥8 days will be considered treatment discontinuation. Number of days of continuous treatment with the site clinician prescribing sublingual or injectable buprenorphine treatment during the 90 days post-randomization among RCT participants
Measured: 90 days
Self-reported protocol satisfaction at day 7
Patient-reported satisfaction with buprenorphine initiation protocol measured by Likert-scale satisfaction survey administered on day 7 follow-up visit
Measured: 7 days
Secondary outcomes (16)
Per protocol and as-treated retention in outpatient buprenorphine treatment at day 90
Similar to the primary intention to treat analysis, though we will be analyzing data and individuals based on actual protocol received and treated, rather than assigned treatment at randomization
Measured: 90 days
Successful buprenorphine initiation within first 7 days
Defined as successfully completing buprenorphine initiation. For LDI treatment arm, this means self-reported completion of initiation "blister pack" during Days 1-6 at clinical follow up and pick up of buprenorphine refill based on prescription data. For DTI, this means administration of initial weekly BRIXADI injection and subsequent monthly BRIXADI or SUBLOCADE buprenorphine injection within 7 days of the initial weekly injection.
Measured: 7 days
Fentanyl use during days 1-7 determiend by urinary drug screen
Concurrent fentanyl use during days 1-7 following buprenorphine initiation, determined by urinary drug screen at day 7 follow-up visit.
Measured: 7 days
Fentanyl use during days 8-30 determined by urinary drug screen
Concurrent fentanyl use during days 8-30 following buprenorphine initiation, determined by urinary drug screen at day 30 follow-up visit.
Measured: 30 days
Fentanyl use during days 31-90 determined by urinary drug screen
Concurrent fentanyl use during days 31-90 following buprenorphine initiation, determined by urinary drug screen at day 90 follow-up visit.
Measured: 90 days
Self-reported concurrent fentanyl use during days 1-7
Concurrent fentanyl use during days 1-7 following buprenorphine initiation, determined by self-reported Timeline Follow Back survey at day 7 follow-up visit.
Measured: 7 days
Self-reported concurrent fentanyl use during days 8-30
Concurrent fentanyl use during days 8-30 following buprenorphine initiation, determined by self-reported Timeline Follow Back survey at day 30 follow-up visit.
Measured: 30 days
Self-reported concurrent fentanyl use during days 31-90
Concurrent fentanyl use during days 31-90 following buprenorphine initiation, determined by self-reported Timeline Follow Back survey at day 90 follow-up visit.
Measured: 90 days
Self-reported number of days of fentanyl use in first 7 days
Number of days of concurrent fentanyl use during days 1-7 following buprenorphine initiation, determined by self-reported Timeline Follow Back survey at day 7 follow-up visit.
Measured: 7 days
Self-reported number of days of concurrent fentanyl use during first 30 days
Number of days of concurrent fentanyl use during days 8-30 following buprenorphine initiation, determined by self-reported Timeline Follow Back survey at day 30 follow-up visit.
Measured: 30 days
Self-reported number of days of concurrent fentanyl use during days 31-90
Number of days of concurrent fentanyl use during days 31-90 following buprenorphine initiation, determined by self-reported Timeline Follow Back survey at day 90 follow-up visit.
Measured: 90 days
Baseline withdrawal symptoms, measured with COWS
At baseline, a Clinical Opioid Withdrawal Score (COWS) survey will be administered and confirmed with the prescribing clinician.
Measured: 0 days
Standardized self-reported daily withdrawal symptom severity over days 1-7 by SOWS
During each of the first 7 days, participants will rate the severity of withdrawal symptoms using standardized Likert-type response scales in a daily diary. Items will be adapted from the validated Subjective Opioid Withdrawal Scale [SOWS] (from 0-4, with 0 being not at all and 4 being extreme) to assess for subjective withdrawal symptoms to minimize participant burden while ensuring reliable data capture.
Measured: 7 days
Standardized self-reported peak withdrawal symptom severity during days 1-7 by SOWS
During each of the first 7 days, participants will rate the severity of withdrawal symptoms using standardized Likert-type response scales in a daily diary. Items will be adapted from the validated Subjective Opioid Withdrawal Scale [SOWS] (from 0-4, with 0 being not at all and 4 being extreme) to assess for subjective withdrawal symptoms to minimize participant burden while ensuring reliable data capture. We will calculate peak withdrawal symptoms during the 7-day period.
Measured: 7 days
Standardized self-reported daily craving symptom severity over days 1-7 by VAS
During each of the first 7 days, participants will rate the severity of craving symptoms using standardized Likert-type response scales in a daily diary. Items will be adapted from the validated Visual Analog Scale [VAS] (from 0-100, with 0 being none at all and 100 being strongest craving ever) to assess for subjective craving symptoms to minimize participant burden while ensuring reliable data capture.
Measured: 7 days
Standardized self-reported peak craving symptom severity during days 1-7 by VAS
During each of the first 7 days, participants will rate the severity of craving symptoms using standardized Likert-type response scales in a daily diary. Items will be adapted from the validated Visual Analog Scale [VAS] (from 0-100, with 0 being none at all and 100 being strongest craving ever) to assess for subjective craving symptoms to minimize participant burden while ensuring reliable data capture. We will calculate the peak craving severity during the first 7 days.
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2026
- Study startJun 2026 (estimated)
- Primary completionMay 2027 (estimated)
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Opioid Use DisorderStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Leslie W Suen, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07469501
- Sponsor's protocol ID
- 1K23DA060329-01
- Other IDs
- 1K23DA060329-01
- Acronym
- COPILOT
- Status last verified
- Mar 2026
- First submitted
- 20 Feb 2026
- Last updated
- 13 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: IPD will not be shared outside of this study's research team.
Publications
Noel M, Abbs E, Suen L, Samuel L, Dobbins S, Geier M, Soran CS. The Howard Street Method: A Community Pharmacy-led Low Dose Overlap Buprenorphine Initiation Protocol for Individuals Using Fentanyl. J Addict Med. 2023 Jul-Aug 01;17(4):e255-e261. doi: 10.1097/ADM.0000000000001154. Epub 2023 Feb 17.
PubMed 37579105Rosenwohl-Mack S, Suen LW, Logan AA, Peterson D, Snyder HR. Outpatient Initiation of 7-Day Injectable Buprenorphine: A Direct-to-Inject Case Series. Subst Use Addctn J. 2025 Oct;46(4):1064-1069. doi: 10.1177/29767342251330412. Epub 2025 Apr 4.
PubMed 40183345
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Buprenorphine Initiation Among Individuals With Opioid Use Disorder Using Fentanyl
- ClinicalTrials.gov ID
- NCT07469501
- Acronym / sponsor ID
- COPILOT / 1K23DA060329-01
- Conditions
- Opioid Use Disorder, Fentanyl
- Keywords
- Buprenorphine initiation, Low-dose initiation, Direct-to-inject initiation, Medication for opioid use disorder, Outpatient treatment for opioid use disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute on Drug Abuse (NIDA)
- Study start
- Jun 2026 (estimated)
- Primary completion
- May 2027 (estimated)
- Study completion
- May 2027 (estimated)
- First posted
- 13 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this pragmatic randomized controlled trial is to compare treatment outcomes of two strategies for initiating buprenorphine treatment (low-dose initiation and direct-to-inject) in adults with opioid use disorder (OUD) who use fentanyl. This study aims to:
- Compare effectiveness of each strategy on treatment retention in a real world, clinical setting, and
- Assess differences between strategies in patient-reported outcomes, including withdrawal symptoms, cravings, drug use, treatment satisfaction, and overall acceptability.
Participants will:
- Be randomized to initiate buprenorphine via a low-dose initiation or direct-to-inject protocol at an outpatient buprenorphine clinic,
- Keep a diary of craving and withdrawal symptoms for the first 7 days after initiation, and
- Visit the outpatient clinic 7, 30, and 90 days after initiation for urinary drug screen and follow-up surveys.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low-dose initiation (LDI) | Active comparator | Drug: Sublingual Buprenorphine (SUBOXONE, Zubsolv, or generic tablets)Participants start 0.5mg sublingual buprenorphine (Subutex) and gradually increase by 0.5-1.0mg daily for 7 days |
| Direct-to-inject (DTI) | Experimental | Drug: Injectable buprenorphineParticipants receive 8-32mg long-acting injectable buprenorphine (Brixadi or Sublocade) on day 1, followed by monthly injections as discussed with the provider |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥ 18 years of age at Visit 1.
- Documentation of an OUD diagnosis as evidenced by meeting two or more of the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) Criteria for Opioid Use Disorder
- Self-reported daily use of fentanyl ≥ 5 out of the past 7 days at baseline,
- Fentanyl-positive urine drug screening at baseline,
- Interest in stopping or reducing fentanyl use,
Key exclusion criteria (6 listed)
- Currently nursing, pregnant, or anticipating pregnancy in the next 6 months
- Methadone-positive urine drug screening at baseline
- Buprenorphine-positive urine drug screening at baseline
- Be unable to provide any locator or contact information at least one contact in addition to themselves
- Any pending legal action that could prevent participation in study activities
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Injectable buprenorphineAlso: Direct-to-inject, Brixadi, Sublocade, Long-acting injectable buprenorphineStarting dose (8-32mg) of long-acting injectable buprenorphine (Brixadi or Sublocade) on day 1, followed by monthly maintenance doses (e.g., 128mg Brixadi or 300mg Sublocade) | Drug | Direct-to-inject (DTI) |
| Sublingual Buprenorphine (SUBOXONE, Zubsolv, or generic tablets)Also: Low-dose buprenorphine initiation, Suboxone, Buprenorphine blister packsStarting dose (0.5mg) of sublingual buprenorphine tablets in blister packs (Brixadi or Sublocade) on day 1, followed by 0.5-1.0mg daily increases in week 1 and maintenance dosing based on shared decision-making with provider | Drug | Low-dose initiation (LDI) |
Primary outcome
Continuous retention in outpatient buprenorphine treatment by day 90
Time frame: 90 days
Receiving continuous treatment with buprenorphine sublingual prescriptions or injections administrations during the 90 days of follow up post-randomization as intended-to-treat. A period without buprenorphine treatment ≥8 days will be considered treatment discontinuation. Number of days of continuous treatment with the site clinician prescribing sublingual or injectable buprenorphine treatment during the 90 days post-randomization among RCT participants
Self-reported protocol satisfaction at day 7
Time frame: 7 days
Patient-reported satisfaction with buprenorphine initiation protocol measured by Likert-scale satisfaction survey administered on day 7 follow-up visit
16 secondary outcomes
Per protocol and as-treated retention in outpatient buprenorphine treatment at day 90
Time frame: 90 days
Successful buprenorphine initiation within first 7 days
Time frame: 7 days
Fentanyl use during days 1-7 determiend by urinary drug screen
Time frame: 7 days
Fentanyl use during days 8-30 determined by urinary drug screen
Time frame: 30 days
Fentanyl use during days 31-90 determined by urinary drug screen
Time frame: 90 days
Self-reported concurrent fentanyl use during days 1-7
Time frame: 7 days
Self-reported concurrent fentanyl use during days 8-30
Time frame: 30 days
Self-reported concurrent fentanyl use during days 31-90
Time frame: 90 days
Self-reported number of days of fentanyl use in first 7 days
Time frame: 7 days
Self-reported number of days of concurrent fentanyl use during first 30 days
Time frame: 30 days
Self-reported number of days of concurrent fentanyl use during days 31-90
Time frame: 90 days
Baseline withdrawal symptoms, measured with COWS
Time frame: 0 days
Standardized self-reported daily withdrawal symptom severity over days 1-7 by SOWS
Time frame: 7 days
Standardized self-reported peak withdrawal symptom severity during days 1-7 by SOWS
Time frame: 7 days
Standardized self-reported daily craving symptom severity over days 1-7 by VAS
Time frame: 7 days
Standardized self-reported peak craving symptom severity during days 1-7 by VAS
Time frame: 7 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2026.
- Background: PubMed 37579105Noel M, Abbs E, Suen L, Samuel L, Dobbins S, Geier M, Soran CS. The Howard Street Method: A Community Pharmacy-led Low Dose Overlap Buprenorphine Initiation Protocol for Individuals Using Fentanyl. J Addict Med. 2023 Jul-Aug 01;17(4):e255-e261. doi: 10.1097/ADM.0000000000001154. Epub 2023 Feb 17.
- Background: PubMed 40183345Rosenwohl-Mack S, Suen LW, Logan AA, Peterson D, Snyder HR. Outpatient Initiation of 7-Day Injectable Buprenorphine: A Direct-to-Inject Case Series. Subst Use Addctn J. 2025 Oct;46(4):1064-1069. doi: 10.1177/29767342251330412. Epub 2025 Apr 4.
- Individual participant dataSharing planned: No. IPD will not be shared outside of this study's research team.
Related trials for Opioid Use Disorder
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Enrolling by invitationObservational study
Development of an Interview-Informed Timeline Follow-Back (TLFB) for Opioid Use in the Era of Fentanyl
Substance Use Disorders (SUDs)
Not yet recruiting
Comprehensive Opioid Management and Breathing During Sleep
Sleep-Disordered Breathing, Chronic Opioid Use
Active, not recruitingPhase 2
Wellcome Leap Psilocybin for OUD
Opioid Use Disorder
Recruiting
Opioid and Pain Treatment in Indigenous Communities (OPTIC) Trial
Opioid Use Disorder, Opioid Misuse
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Leslie W Suen, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Injectable buprenorphine and Sublingual Buprenorphine (SUBOXONE, Zubsolv, or generic tablets) in people with Opioid Use Disorder and Fentanyl, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 13 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Leslie W Suen, MD (628-206-6007, leslie.suen@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Continuous retention in outpatient buprenorphine treatment by day 90 (time frame: 90 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07469501, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2026.