A Phase 2 interventional study of CAM2038 and Buprenorphine Sublingual Product in Opioid-use Disorder, sponsored by Yale University. Completed at 35 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-01-10.
Sponsored by Yale University · Phase 2, Interventional, and Treatment
This study will (1) recruit, train and provide resources to approximately 30 Emergency Department (ED) sites throughout the U.S. using implementation facilitation strategies to provide ED-initiated buprenorphine (BUP) for patients presenting with opioid use disorder (OUD) who are not receiving medications for opioid use disorder (MOUD). Once implementation is adequately achieved, the sites will (2) conduct a randomized controlled trial (RCT) to compare the effectiveness of sublingual buprenorphine (SL-BUP) versus extended-release buprenorphine (XR-BUP) on ED patients' engagement in formal addiction treatment 7-days after their ED visit. In addition, in an ancillary component of the study, the investigators will (3) assess the use of XR-BUP in ED patients with Clinical Opioid Withdrawal Scale (COWS) scores \< 8 in a case series to potentially expand the eligibility of patients in the larger RCT to those presenting with little to no opioid withdrawal symptoms. Finally, the investigators will (4) develop and validate ED electronic health record (EHR) opioid-related phenotypes, both of which will inform the main RCT.
The study will be comprised of four components as outlined below:
Site implementation component:
In this component, the investigators will use previously developed implementation facilitation strategies and resources to train ED providers and staff at approximately 30 diverse EDs in treatment initiation with SL-BUP and XR-BUP and develop ED buprenorphine protocols and procedures. The investigators anticipate that this will result in a minimum of 24 sites (80%) that will meet the implementation milestones for competence in ED-initiated BUP using standard SL and XR-BUP inductions.
Effectiveness RCT component:
This component is a large pragmatic RCT using a Hybrid Type 1 Effectiveness-Implementation design. Sites that satisfactorily complete the site implementation component will be activated on a rolling basis for the RCT after demonstrated implementation milestones have been met. In this Hybrid Type 1 design the primary research question is the effectiveness of SL-BUP induction compared with that of XR-BUP on the primary outcome measure of engagement in formal addiction treatment at 7-days post ED visit. This design also allows us to gather information and report on implementation processes.
Ancillary component - XR-BUP Induction for patients with COWS \< 8:
This observational case series will begin in advance of the Effectiveness RCT component at approximately 4 ED sites with extensive experience in ED-initiated BUP. The investigators will collect quantitative and qualitative data on the use of XR-BUP in ED patients with low COWS scores for approximately 75 patients. Sites will receive a supply of XR-BUP for provision to up to 5 patients with a COWS score > 8. The purpose is to pre-study the procedures at the four ancillary study sites on treating OUD patients with XR-BUP prior to initiation of the ancillary component. Data collected from this pre-study will not be included in the analysis of the ancillary and effectiveness RCT component. These initial up to 20 pre-study patients will meet all other study criteria and undergo all assessments. It is anticipated that the information collected from the 75 patients in the ancillary component will allow for modification to the larger Effectiveness RCT by expanding eligibility criteria to include patients with COWS \<8.
Development and validation of EHR ED opioid-related phenotypes component:
In this component, the investigators will develop EHR phenotypes of opioid-related illnesses that accurately and automatically characterize patient conditions, enhance the ability to actively monitor and surveil, and better identify representative samples and patients potentially eligible for study inclusion, leading ultimately to an enhanced inclusion and understanding of opioid-related conditions. At the primary Yale New Haven Health System sites, the phenotypes (rules- and machine learning-based) will be iteratively developed and internally validated. The rules-based phenotype will be mapped to a common data model and externally validated at 4 trial sites.
The primary focus of this clinicaltrials.gov registration are the RCT outcomes. Implementation and ancillary outcomes will be identified as secondary outcomes for the purpose of this clinicaltrials.gov registration
1,439 studies on the registry are indexed under Opioid-Related Disorders; 291 are open to participants now.
This study's enrollment of 2,000 is above the median of 62 across 1,145 interventional studies indexed under Opioid-Related Disorders.
Browse Opioid-Related Disorders studies →Yale University is the lead sponsor of 1,763 studies on the registry; 292 are open to participants now.
Of its 217 completed or terminated interventional studies of FDA-regulated products, 128 (59%) have results posted.
Counted across the registry records on this site, refreshed daily.
RCT Component:
Inclusion Criteria:
Exclusion Criteria:
Ancillary Component:
Inclusion Criteria:
Exclusion Criteria:
Injectable buprenorphine
Drug: CAM2038
Sublingual buprenorphine
Drug: Buprenorphine Sublingual Product
Patients will receive a 24 mg dose of injectable CAM2038 in the ED on Day 0.
COWS ≥ 8: Patients will receive 4mg of SL-BUP for a COWS score of 8-12 (mild withdrawal). After 30-45 minutes if tolerated and no unanticipated adverse reactions, an additional 4mg can be administered for a total of 8mg in the ED. Patients presenting with moderate-severe withdrawal (COWS \>≥ 13) will receive an initial dose of 8mg SL-BUP. All patients will receive a buprenorphine prescription and instructions for additional BUP doses to allow for up to a dose of 12mg if needed, and for 16mg each subsequent day until their scheduled follow up appointment for ongoing MOUD (medications for opioid use disorder). COWS 4-7: Patients will be provided with a uniform set of instructions to guide unobserved (home) induction. They will be prescribed doses of SL-BUP to allow them to take dose up to 12mg in the 24 hours after discharge. All patients will also receive a buprenorphine prescription for 16mg each subsequent day until their scheduled follow up appointment for ongoing MOUD.
RCT Component: Patient engagement (yes/no) in formal addiction treatment at 7 days post randomization
Engagement in formal addiction treatment will be defined as enrollment and receiving formal addiction treatment on the 7th day post randomization, confirmed by contact with the facility and/or treating clinician. Formal addiction treatment will be operationally defined as those treatments consistent with the American Society of Addiction Medicine's levels of care (1-4) and can include a range of clinical settings including office-based providers of BUP or naltrexone, opioid treatment programs (OTPs), intensive outpatient, inpatient, or residential treatments. Patients do not need to be receiving MOUD at 7 days to be considered engaged in formal addiction treatment. Participation in a mutual-help program such as Alcoholics Anonymous (AA) or (Narcotics Anonymous) NA alone will not be considered as engagement in formal addiction treatment. Additional analyses evaluating the effects of patient and site characteristics will also be conducted.
Time frame: 7 days post randomization
RCT Component: Engagement in MOUD (yes/no) at 7 days post randomization
self-report verified with treatment provider(s)
Time frame: 7 days post randomization
RCT Component: Patient engagement (yes/no) in formal addiction treatment at 30 days post randomization
Engagement in formal addiction treatment will be defined as enrollment in formal addiction treatment on the 30th day post randomization, confirmed by direct contact with the facility and/or treating clinician. Formal addiction treatment will be operationally defined as those treatments consistent with the American Society of Addiction Medicine's levels of care (1-4) and can include a range of clinical settings including office-based providers of BUP or naltrexone, OTPs, intensive outpatient, inpatient, or residential treatments. Patients do not need to be receiving MOUD on the 30th day post randomization to be considered engaged in formal addiction treatment. Participation in a mutual-help program such as Alcoholics or Narcotics Anonymous alone will not be considered as engagement in formal addiction treatment. Additional analyses evaluating the effects of patient and site characteristics will also be conducted.
Time frame: 30 days post randomization
RCT Component: Patient Engagement in MOUD (yes/no) at 30 days post randomization
self report verified with treatment provider(s)
Time frame: 30 days post randomization
RCT Component: Self-reported days of illicit opioid use (past 7 days) at 7 days post randomization
The Timeline Follow-back procedure will be used to elicit the patient participant's self-reported days of use of opioids.
Time frame: 7 days post randomization
RCT Component: Self-reported days of illicit opioid use (past 7 days) at 30 days post randomization
The Timeline Follow-back procedure will be used to elicit the patient participant's self-reported days of use of opioids.
Time frame: 30 days post randomization
RCT Component: Craving scores at 7 days post randomization
The investigators will use visual analogue scales (VAS) to assess craving, desire to use opioids and need to use opioids with a scale of 0-100.
Time frame: 7 days post randomization
RCT Component: Healthcare services utilization (past 30 days) regarding ED visits and hospitalizations at 30 days post randomization
A brief, structured interview regarding health care utilization (inpatient and outpatient) will be used, which collects information on the type and amount of services received. This includes ED visits, hospitalizations, primary medical care visits (excluding those for BUP treatment and self-help sources of support (e.g., NA).
Time frame: 30 days post randomization
RCT Component: Patient satisfaction with BUP at 7 days post randomization
The investigators will modify the patient satisfaction scale where overall experience is rated from 1 to 5 (1 is completely ineffective and 5 is completely effective) and treatment characteristics are rated 1 to 7 (1 is not important and 7 is extremely important) based on previous published data.
Time frame: 7 days post randomization
RCT Component: Overdose Events at 30 days post randomization
Assessment of past 30-day overdose events will be completed at 30 days post study enrollment. In addition, Site PIs will search local electronic medical records for fatal and non-fatal overdose events.
Time frame: 30 days post randomization
Ancillary Component: Proportion of participants that experience a 5 or greater increase in COWS score within 4 hours of of XR-BUP administration
Clinical Opiate Withdrawal Scale (COWS) - the COWS is a validated measure of the severity of opioid withdrawal that consists of 11 subjective and objective items. Scores on the individual items are combined to a single overall score that has been used to determine the SL-BUP induction strategy. COWS scoring, and interpretation is as follows: Score: 5-12 = mild opioid withdrawal; 13-24 = moderate opioid withdrawal; 25-36 = moderately severe opioid withdrawal; more than 36 = severe opioid withdrawal.
Time frame: Within 4 hours of XR-BUP administration
Ancillary Component: Proportion of participants that transition to moderate withdrawal (COWS 13-24) within 4 hours of XR-BUP administration
Clinical Opiate Withdrawal Scale (COWS) - the COWS is a validated measure of the severity of opioid withdrawal that consists of 11 subjective and objective items. Scores on the individual items are combined to a single overall score that has been used to determine the SL-BUP induction strategy. COWS scoring, and interpretation is as follows: Score: 5-12 = mild opioid withdrawal; 13-24 = moderate opioid withdrawal; 25-36 = moderately severe opioid withdrawal; more than 36 = severe opioid withdrawal.
Time frame: Within 4 hours of XR-BUP administration
Ancillary Component: Proportion of participants that experience clinician determined precipitated withdrawal within 1 hour of XR-BUP administration
Assessment of Proportion of participants that experience clinician determined precipitated withdrawal within 1 hour of XR-BUP administration.
Time frame: Within 1 hour post XR-BUP injection
RCT Component: Cost effectiveness of XR-BUP compared to SL-BUP using ICER (incremental cost-effectiveness ratio): Engagement
The final outcome measure for the cost-effectiveness analysis is the ICER (incremental cost-effectiveness ratio), which includes the relevant cost differential between the study arms in the numerator, and the difference in a chosen effectiveness measure in the denominator. 3 types of ICERs will be generated, each one with a different effectiveness measure (engagement in formal addiction treatment at 30 days; quality-adjusted life-years (QALYs) gained; and Abstinent Years). The reason being that different ICERs are more relevant to certain potential stakeholder groups than others.
Time frame: 7 days post randomization
RCT Component: Cost effectiveness of XR-BUP compared to SL-BUP using ICER (incremental cost-effectiveness ratio): QALYs
The final outcome measure for the cost-effectiveness analysis is the ICER (incremental cost-effectiveness ratio), which includes the relevant cost differential between the study arms in the numerator, and the difference in a chosen effectiveness measure in the denominator. 3 types of ICERs will be generated, each one with a different effectiveness measure (engagement in formal addiction treatment at 30 days; quality-adjusted life-years (QALYs) gained; and Abstinent Years). The reason being that different ICERs are more relevant to certain potential stakeholder groups than others.
Time frame: 7 days post randomization
RCT Component: Cost effectiveness of XR-BUP compared to SL-BUP using ICER (incremental cost-effectiveness ratio): Abstinent Years
The final outcome measure for the cost-effectiveness analysis is the ICER (incremental cost-effectiveness ratio), which includes the relevant cost differential between the study arms in the numerator, and the difference in a chosen effectiveness measure in the denominator. 3 types of ICERs will be generated, each one with a different effectiveness measure (engagement in formal addiction treatment at 30 days; quality-adjusted life-years (QALYs) gained; and Abstinent Years). The reason being that different ICERs are more relevant to certain potential stakeholder groups than others.
Time frame: 7 days post randomization
RCT Component: Cost effectiveness of XR-BUP compared to SL-BUP using ICER (incremental cost-effectiveness ratio): Engagement
The final outcome measure for the cost-effectiveness analysis is the ICER (incremental cost-effectiveness ratio), which includes the relevant cost differential between the study arms in the numerator, and the difference in a chosen effectiveness measure in the denominator. 3 types of ICERs will be generated, each one with a different effectiveness measure (engagement in formal addiction treatment at 30 days; quality-adjusted life-years (QALYs) gained; and Abstinent Years). The reason being that different ICERs are more relevant to certain potential stakeholder groups than others.
Time frame: 30 days post randomization
RCT Component: Cost effectiveness of XR-BUP compared to SL-BUP using ICER (incremental cost-effectiveness ratio): QALYs
The final outcome measure for the cost-effectiveness analysis is the ICER (incremental cost-effectiveness ratio), which includes the relevant cost differential between the study arms in the numerator, and the difference in a chosen effectiveness measure in the denominator. 3 types of ICERs will be generated, each one with a different effectiveness measure (engagement in formal addiction treatment at 30 days; quality-adjusted life-years (QALYs) gained; and Abstinent Years). The reason being that different ICERs are more relevant to certain potential stakeholder groups than others.
Time frame: 30 days post randomization
RCT Component: Cost effectiveness of XR-BUP compared to SL-BUP using ICER (incremental cost-effectiveness ratio): Abstinent Years
The final outcome measure for the cost-effectiveness analysis is the ICER (incremental cost-effectiveness ratio), which includes the relevant cost differential between the study arms in the numerator, and the difference in a chosen effectiveness measure in the denominator. 3 types of ICERs will be generated, each one with a different effectiveness measure (engagement in formal addiction treatment at 30 days; quality-adjusted life-years (QALYs) gained; and Abstinent Years). The reason being that different ICERs are more relevant to certain potential stakeholder groups than others.
Time frame: 30 days post randomization
Plan to share: Yes — In line with the National Institutes of Health Helping to End Addiction Long-term (NIH HEAL) Initiative Public Access and Data Sharing Policy, publications and underlying primary data will be made available to the public.
Time frame: Data will be made available after 1) the primary paper has been accepted for publication, or 2) the data is locked for more than 18 months, whichever comes first.
This study is completed, as verified in Jan 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: CAM2038