Emergency Department-initiated standard versus high-dose buprenorphine induction (ENVISION): a randomised clinical trial protocol

Abstract

Introduction

The initiation of buprenorphine for patients with opioid use disorder (OUD) in the emergency department (ED) has been associated with improved outcomes including reduced ED visits and increased treatment engagement. Though both standard-dose (8 mg buprenorphine equivalent) and high-dose (24 mg buprenorphine equivalent) strategies to initiate buprenorphine have been used in the ED, no prospective trials comparing outcomes among patients receiving these treatments have been reported.

Methods and analysis

This multisite randomised clinical trial is a multisite double-blind, double-dummy, randomised clinical trial enrolling 360 emergency department patients with moderate-to-severe OUD. Enrolled patients will be randomised to one of two study arms: standard-dose induction or high-dose induction, both provided in the ED. This study will engage, train and provide resources to five EDs throughout the US to recruit patients with untreated OUD into a randomised clinical trial. The primary aim is to evaluate the effects of the standard-dose induction and high-dose induction on rates of OUD treatment participation within 10 days post-randomisation. The secondary aims are to evaluate differences between standard-dose induction and high-dose induction on the outcomes of opioid craving, opioid withdrawal symptoms and illicit drug use assessed during 10 days post randomisation and evaluate the effects between treatment arms on rates of OUD treatment participation within 30 days post randomisation.

Ethics and dissemination

This study is funded by the National Institute on Drug Abuse and has been approved by the WCG Instutitional Review Board. It has been registered at clinicaltrials.gov. This study will inform the strategy for treatment initiation with buprenorphine among diverse ED settings and will provide ongoing evidence to support the safety and efficacy of initiating treatment for OUD in the ED.

Trial registration number

NCT06494904.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• This study uses a rigorous double-blind, double-dummy, randomised clinical trial study design to compare two dosing strategies for the initiation of buprenorphine in emergency department patients with untreated opioid use disorder.

• The primary outcome of treatment engagement within ten days is objectively verified with treatment facility rather than by self-report.

• Housing instability and other contextual factors may pose challenges in our ability to reach participants for follow-up assessments; thus we have optimised our procedures to maximise success.

• This prospective study has the potential to change routine emergency department care for initiating treatment for opioid use disorder in the emergency department with buprenorphine.

Introduction

Background, rationale and objectives

Drug overdoses in the USA have recently begun to decline following decades of increases. However, there were still over 80 000 drug overdose deaths in the USA during 2024, including over 54 000 involving opioids.¹ The treatment of opioid use disorder (OUD) with buprenorphine (BUP) or methadone has been associated with improved quality of life, reduced drug use, diminished HIV/hepatitis C transmission, reduced opioid overdose and decreased all-cause mortality.^{2 3} With only 17% of individuals with OUD receiving medications for opioid use disorder (MOUD) treatment,⁴ opioid overdose remains a leading cause of unintentional death for US adults. Emergency departments (EDs) serve the socially vulnerable, racial and ethnic minorities who are currently experiencing disparate rises in overdose and access to MOUD.⁵ Thus, EDs have the potential to mitigate these disparities in MOUD access. Narrowing the treatment gap by expanding access to MOUD beyond specialised drug treatment settings is widely viewed to be a public health priority, and the ED, offering access 24 hours, 7 days a week, 365 days a year, is a logical touch point for intervention.⁵ ED patients have a disproportionately high prevalence of OUD, and for many, the ED is the primary or only access point in the healthcare system.^{6 7} Patients seen in the ED after opioid overdose have a notable 5% 1-year mortality, with a substantial number of deaths occurring in the first 2 days after discharge.⁸

Initiating MOUD treatment in the ED is recommended by consensus guidelines from the American College of Emergency Physicians,⁹ though practices for initiating BUP in the ED continue to evolve.^{10 11} Protocols for ED induction are widely shared on websites,¹²,¹⁴ with the BUP initiation app¹⁵ recommending 4–8 mg of BUP for patients with a Clinical Opioid Withdrawal Scale¹⁶ (COWS) score of 8 or higher and unobserved home initiation for those in minimal withdrawal.¹⁷ Though practices vary widely, the Food and Drug Administration (FDA) product insert still recommends treatment initiation with divided doses up to 8 mg of BUP for the treatment of opioid withdrawal on day 1, which is still practice in some EDs,¹⁸ although the landmark randomized clinical trial ED-initiated BUP study published in 2015 started all ED patients receiving BUP at a single dose of 8 mg.¹⁶

Anecdotally, practitioners are concerned about BUP-precipitated withdrawal, particularly with patients using synthetic opioids such as fentanyl, and both low-dose initiation and high-dose initiation (HDI) strategies have been used without rigorous testing.¹⁹ An accelerated induction process that achieves therapeutic BUP levels in less than 3–4 hours compared with the typical 2–3 days could potentially increase safety and comfort during the crucial gap between ED discharge and engagement in continuing treatment by limiting illicit opioid use and encouraging follow-up visits with OUD treatment providers, while diminishing withdrawal and craving which may also increase engagement in follow-up treatment. Previous studies have shown non-inferiority of thrice weekly BUP dosing of 34 or 44 mg BUP compared with 16 mg BUP daily, highlighting the lasting effects of larger doses of BUP.²⁰ In the ED, administering larger doses of BUP could improve outcomes by providing more sustained relief of withdrawal and craving after a single dose, allowing patients additional time to arrange transportation, obtain medications from the pharmacy and address other needs during this crucial post-discharge window.

Interest in high-dose BUP initiation strategies has been increasing, although no prospective clinical trials have been reported. A recent retrospective review of 579 ED encounters of ED-BUP at a single site revealed that high-dose induction was safe and well tolerated, with no cases of respiratory depression and an overall low rate of precipitated withdrawal that was not dose-related.²¹,²³ Thus, our team proposed a National Drug Abuse Treatment Clinical Trials Network (CTN) study, CTN-0145: Emergency department-iNitiated standard vs hIgh doSe buprenorphIne inductiON (ENVISION). This paper describes the protocol for CTN-0145 (ENVISION).

Methods

Study design

ENVISION is a multisite double-blind, double-dummy, randomised clinical trial enrolling ED patients with untreated moderate-to-severe OUD (n=360) across five EDs. The study will compare standard-dose initiation (SDI) and high-dose initiation (HDI) on rates of participation in OUD treatment within 10 days post randomisation, and opioid withdrawal symptoms, opioid craving and use of illicit and non-prescribed drugs. For this study, we have defined SDI as equivalent to 8 mg of BUP based on the initial ED induction dose in the landmark ED-initiated BUP study¹⁶ and subsequent protocols for initiating BUP in the ED.^{14 24} A high-dose BUP initiation has been previously defined as initiating BUP at doses between 12 mg (the upper limit of FDA BUP/naloxone label for day 1)¹⁸ and >32 mg²¹. For this study, we defined HDI as treatment initiation with the equivalent of 24 mg of BUP based on existing protocols and clinical practice along with pragmatic reasons, such as hypothesised differences between outcomes based on dosing and factors associated with medication blinding and administration.

At the time of study start, Zubsolv was the only BUP/naloxone formulation with a commercially available placebo formulation that matched the appearance, taste and colour of active BUP/naloxone medication tablets. Studies show that Zubsolv 5.7/1.4 BUP/naloxone tablet is closely bioequivalent to Suboxone 8/2 mg of BUP/naloxone and has similar efficacy for treating OUD.²⁵

The primary aim of this study is to evaluate the effects of SDI and HDI on rates of OUD treatment participation within 10 days post randomisation. Secondary aims include evaluation of differences between SDI and HDI on the outcomes of opioid craving, opioid withdrawal symptoms and illicit drug use assessed during 10 days post randomisation and an evaluation of the effects of the SDI and HDI on rates of OUD treatment participation within 30 days post randomisation. Exploratory aims will also include rates of precipitated withdrawal, the use of fentanyl and other polysubstance use such as stimulants, sedatives, alcohol; overdose rates and outcomes characterised by different races, housing instability and other social determinants of health.

The study design was overseen by an independent Protocol Review Board in coordination with the National Institute on Drug Abuse (NIDA) Clinical Trials Network, the Emmes Company Data and Statistics Center (DSC) and the Emmes Company Clinical Coordinating Center (CCC). Patients and the general public were not involved in the design and conduct of this clinical trial, although the planning of this trial has been informed by qualitative research with ED patients with OUD focused on the initiation of treatment for OUD in the ED.²⁶,²⁸

This study will be conducted as an Investigational New Drug (IND) study by the US FDA, and in compliance with US Code of Federal Regulations 21 CFR 312.30(b), 45 CFR 46 and its subparts, and the International Council for Harmonization Good Clinical Practice Guidelines (ICH E6 R2). As depicted in online supplemental table 1, study enrolment started in December 2024 and is on track to finish enrolment in May 2027.

Site selection

Approximately five EDs throughout the USA will recruit ED patients presenting with untreated OUD to participate in the trial. All sites have had extensive experience with enrolling ED patients with OUD into an earlier BUP trial, ED INNOVATION (CTN-0099).²⁹ Selected sites included EDs at Maine Medical Center in Portland, Maine; Cooper University in Camden, New Jersey; University of Utah in Salt Lake City, Utah; Highland Hospital in Oakland, California; and San Leandro Hospital in San Leandro, California.

Participants

Potential participants must meet all the inclusion criteria to be eligible to participate in the study and none of the exclusion criteria. All patients enrolled into the study must: (1) be between 18 and 65 years of age; (2) be treated in the ED during study screening hours; (3) meet the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 diagnostic criteria for moderate-to-severe OUD; (4) have a COWS score of ≥8 at enrolment; (5) have a urine toxicology test that is positive for opioids and (6) be able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study.

All patients enrolled into the study must not: (1) have a medical or psychiatric condition that requires hospitalisation at the time of the index ED visit; (2) have a known hypersensitivity reaction to BUP/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 the index ED visit; (8) be unwilling to follow study procedures (eg, unwilling to provide permission to contact referral provider/programme or unavailable for the follow-up assessments); (9) have prior enrollment in the current study; (10) have received MOUD treatment within the past 7 days; (11) be pregnant as determined by human chorionic gonadotropin (hCG) testing at the index ED visit; (12) have a respiratory rate <8 or oxygen saturation <93%; and (13) be a participant in any other clinical trial in which medication(s) are being delivered or the use of an investigational drug or device within the last 30 days.

Participant compensation is in accordance with the Instutitional Review Board (IRB) of record’s policies and procedures and approved by the IRB. Enrolled participants will be compensated with a US$50 gift card for completing the enrollment process at the initial ED visit, and an additional US$100 for completing the Day 10 Telephone Interview and another US$100 for completing the Day 30 Telephone Interview, for a maximum of US$250 at study completion.

Screening procedures

Research Assistants (RAs) will be available in the EDs, including during evenings and weekends, to ensure success with enrollment at each ED site. The RA will identify patients seen in the ED by screening and reviewing the electronic health record (EHR) track boards and by clinician referral. The RA will keep a log of all patients screened and excluded and the reasons for exclusion. Potential participants identified will be evaluated by an RA and Site principal investigator (PI) for eligibility.

Potential participants will be asked for verbal consent to complete a set of screening assessments that includes questions about non-prescribed opioid use, including heroin, fentanyl and non-medical use of prescription opioids in the past 30 days (ED Health Quiz screener). The screener will also include questions about safety, tobacco and alcohol use.^{8 9}

Potential study participants who report any non-prescribed opioid use in the past month will complete a 7-day timeline recall of opioid use. If any non-prescribed opioid use is reported during the past 7 days, a brief structured diagnostic interview with questions based on the DSM-5 criteria will be used to evaluate for the presence of moderate or severe OUD. If the urine tests are positive for any opioid (other than methadone) and the patient meets all eligibility criteria, the patient will be offered participation in the trial and written informed consent will be obtained. Study procedures have been optimised to minimise delay to study medication administration.

Enrollment and randomisation

Once the study eligibility is confirmed and the written consent (online supplemental file 2) has been obtained by the RA, the patient will be considered enrolled in the study. The informed consent form for this study includes an optional section for participants to indicate interest in being contacted by the study team for future IRB approved studies. The enrolment procedures will be captured through a centralised process managed by the DSC. Enrolled participants will be randomised 1:1 to SDI or HDI by the DSC. Only the DSC staff overseeing the random assignment schedule, a few designated CCC staff and the central research staff preparing the study medication will be unblinded; all other study personnel and participants will remain blinded to treatment arm until the nationwide completion of the trial and the database is formally locked. Figure 1 shows the screening and enrolment flowchart.

Figure 1. Screening and enrolment processes. COWS, Clinical Opioid Withdrawal Scale; DSM-5, Diagnostic and Statistical Manual of Mental Disorders-5; ED, emergency department; PI, principal investigator.

ED intervention and procedures

Uniform BUP induction protocols will be used for all enrolled participants, who must have a COWS of at least 8. Enrolled participants randomised to SDI will receive three tablets; one 5.7 mg BUP Zubsolv tablet and two placebo tablets. Those randomised to HDI will receive three 5.7 mg BUP Zubsolv tablets. Tablets will be administered sublingually by ED staff with the RA present, and the RAs will be trained to verify medication dissolution under the participant’s tongue.

All participants will be observed for 2 hours post-study medication administration with repeated COWS at hours 1 and 2. These participants will be discharged with a prescription for 16 mg of BUP based on patient factors prior to discharge.

For participants with objectively worsening withdrawal symptoms (ie, vomiting, diarrhoea, increased agitation, nausea, etc) after study medication administration but before the planned 1-hour COWS evaluation, a COWS will be documented. If the COWS score suggests worsening or precipitated withdrawal, additional BUP or other medications may be given as described below at clinician discretion.

Other related symptoms, worsening or precipitated withdrawal

Table 1 shows medications that may be given for associated symptoms of withdrawal. If within 2 hours after the initial study medication dosing, any participant with isolated, related symptoms such as nausea (which may be a side effect of BUP) can receive anti-nausea medications. Similarly, other isolated symptoms can be treated as shown in table 1.

Table 1. Medications for associated symptoms of withdrawal.

Symptom	Medications
Abdominal cramps or pain	Acetaminophen, NSAIDs: ibuprofen; ketorolac (Toradol)
Nausea	Ondansetron (Zofran), prochlorperazine (Compazine), promethazine (Phenergan)
Elevated blood pressure, tachycardia, anxiety or restlessness	Clonidine, lofexidine
Restlessness	Pramipexole or ropinirole

NSAID, Nonsteroidal Anti-Inflammatory Drug.

Any participant with an increase in COWS of ≥5 points in objective COWS components (eliminating nausea which can be a side effect of the BUP administration³⁰ within 2 hours of initial administration may be experiencing worsening or prolonged withdrawal and can receive an additional 8 mg of BUP sublingual (SL). If the clinician suspects precipitated withdrawal based on a rapidly deteriorating course, 16 mg of BUP or more can be administered.

All participants who experience an increase in COWS of ≥5 points, including objective COWS components within 2 hours of study medication administration, will have their clinical course reviewed by pre-selected blinded expert consultants external to the research team to evaluate for the diagnosis of precipitated withdrawal. This determination will be based on the severity of the withdrawal signs and symptoms, the rapidity of the onset of withdrawal symptoms, and clinical factors (eg, timing since last use of an opioid agonist(s), type(s) of opioid agonist, duration of action of opioid agonist(s) used and route of administration).

Referral for ongoing treatment

Referral for ongoing MOUD will be made based on participant preference and insurance and will be identical for both treatment arms. Participants may be referred to clinicians that offer BUP formulations or methadone as their ongoing MOUD. This will allow participants to receive referrals to federally licensed opioid treatment programmes, ‘bridge’ clinics or other office-based clinicians. All participants will be provided with naloxone and a wallet card identifying the fact they were enrolled in an ED-BUP dosing initiation study and a printed reminder about the planned follow-up dates prior to discharge.

Medication blinding

The study participant, clinical staff and research staff will be blinded and have no knowledge of study arm randomisation. Designated centralised DSC staff who oversaw the development of an automated computerised randomisation process, and the study medications were prepared by unblinded central staff prior to the shipment of medication to sites in numbered medication sachets. All other study personnel and participants will remain blinded to treatment arm until the nationwide completion of the trial and the database is formally locked. Detailed information on the study procedures regarding the double-blinding will be contained in a standalone Blinding Management Plan and Study Site Blinding Plan. A Data and Safety Monitoring Board (DSMB) will review study data throughout the course of the trial in a blinded fashion (eg, masked treatment assignments).

After study medication administration, the RA will independently administer a brief assessment to both the study participant and to the ED staff who administered the medication (ie, nurse) to evaluate which medication dose they believe was administered. A Blinding Management Plan is in place should there be an unanticipated need to break the blind for a specific study participant before completion of the trial, although no clear circumstances in which we anticipate this need have been identified.

Assessments

Study assessments will be administered in person during the Index ED visit and by telephone at 10 days and 30 days post randomisation. Participants will receive pre-paid phones to answer daily electronic surveys for 10 days. Engagement in OUD treatment within 10 days after randomisation will be assessed by direct contact with the OUD treatment clinician/programme provided by the participant and/or EHR review.

The baseline and follow-up assessments are brief, balancing the value of comprehensive data against feasibility, to minimise assessment reactivity that can obscure treatment effects. Excluding collection of study participant characteristics and locator information, the participant baseline data will include a brief instrument assessing health status, healthcare utilisation, overdose events, past 7-day alcohol and drug use including opioids using the Timeline Follow-Back^{31 32} method and use of other substances. Table 2 provides the schedule of study assessments. The total expected time burden is less than 30 min for baseline, 10-day and 30-day assessments. Daily assessments should take less than 5 min to complete.

Table 2. Schedule of study assessments.

Instrument/activity	Study assessments
	(Index ED visit 0)		Days 1–10	Day 10	Day 30
	Screen	Baseline	Tablet/phone	Phone	Phone
Verbal informed consent	X
ED health quiz	X
DSM-5	X
Urine toxicology	X
COWS	X	X
Pregnancy test	X
Randomisation enrollment	X
Written informed consent, research authorisation, release of information	X
Demographics		X
Additional demographics		X
Locator information form		X		X
Treatment administration record		X
Timeline follow-back (TLFB)		X			X
Crime and criminal justice		X			X
Health Related Behaviour Survey (HRBS)		X			X
Patient Health Questionnaire (PHQ-9)		X			X
Athens Insomnia Scale		X			X
Daily craving, withdrawal and use			X

COWS, Clinical Opioid Withdrawal Scale; DSM-5, Diagnostic and Statistical Manual of Mental Disorders-5; ED, emergency department.

Outcome measures

The primary outcome measure is the proportion of patients in each of the two study arms participating in OUD treatment within 10 days after randomisation. OUD treatment will be defined based on the American Society of Addiction Medicine Criteria Levels of Care 1–4.

The secondary outcome measures are defined as the maximum daily opioid craving and opioid withdrawal ratings self-reported using Visual Analogue Scales and the number of days with illicit opioid and other substance use based on self-reported data obtained daily during the first 10 days post randomisation. These outcomes will be represented by continuous variables. We will also assess the proportion of patients in each study arm participating in OUD treatment within 30 days of randomisation.

Adverse events and serious adverse events

Adverse events will be captured and reported through the AE reporting mechanisms. The reporting period for AEs and serious adverse events (SAEs) for the trial starts at randomisation and ends at the last study visit, day 30 after randomisation. AEs and SAEs are collected when participants return to the ED, if they are reported during nonscheduled follow-ups and based on any information reported during the 10-day or 30-day follow-ups. Formal medical record abstraction is done by the RA after 30 days for ED visits and hospitalisation.

Data quality and monitoring

Qualified monitors will oversee aspects of site conformity to make certain the site staff is operating within the confines of the protocol and in accordance with Good Clinical Practice. This includes but is not limited to protocol compliance, documentation auditing, monitoring of drug disposition and ensuring the informed consent process is being correctly followed and documented.

Statistical design and analyses

Nominal, categorical and ordinal data collected in the proposed research will be summarised using frequencies and percentages. Continuous variables will be summarised using descriptive statistics and relevant measures of central tendency including the means, SD, medians and other indices of ranges, variability and distributional characteristics. All analyses will follow the intention to treat principle.

Randomisation

The DSC statistician will generate the randomisation schedule using balanced blocks of varying sizes within strata to ensure lack of predictability along with relative equality of assignment across treatment groups. The DSC statistician will review randomisation data on a regular basis to ensure that the scheme is being implemented according to plan. If a participant drops out of the study at any point after randomisation, the randomisation slot will not be reallocated to a new participant.

At each study site, the randomisation will be stratified by the following factors: sex at birth (male/other); amphetamine, methamphetamine or cocaine positive urine toxicology (yes/no); and housing instability (yes/no).

Statistical methods for primary and secondary outcomes

The statistical significance of the primary hypothesis will be tested using a mixed-effects logistic regression³² also known as a hierarchical logistic regression³³ with the treatment (SDI vs HDI) as a fixed effect. A statistically significant intervention effect with significantly higher odds of OUD treatment engagement among patients who received HDI compared with SDI will be considered supportive of this hypothesis. This analysis will include additional predictors to explore the effects of patient characteristics on the observed differences in the primary outcome. The hierarchical logistic regression is preferable to other simpler methods as it allows the inclusion of covariates in the analytical model to account for potential between-group differences and correlations between observations on different individuals within participant groups. The proposed analytical model will also allow the evaluation of differential effects of sex, race, ethnicity, insurance types and housing stability on the primary outcome.

The statistical significance of the secondary outcomes will be tested using the mixed-models repeated measures analysis of variance procedure. The mixed-models procedure is designed for unbalanced repeated measures with missing data, allowing for intrasubject serial correlation and unequal variance and covariance structure across time.^{34 35} We will use the mixed-models procedure for analysing repeated measures data with fixed and random effects to evaluate intervention group assignment effect on these continuous and repeated outcome measures.

We will also use linear mixed-effects models to test for between group and time main effects and their interactions on continuous secondary outcome measures. In those analyses, participants will be the clustering factor and we will select the best-fitting variance-covariance structure based on Akaike’s Information Criterion.³⁶ Mixed models are designed for unbalanced repeated measures with missing data, allowing for intra-subject serial correlation and unequal variance and covariance structure across time. Sensitivity analyses with selection and pattern mixture models will be performed to assess how robust the results are if data are not missing at random. The analytical models described above will also allow us to evaluate potential differential effects of key patient characteristics including sex, race, ethnicity, insurance type, housing instability and other important factors including the use of fentanyl, stimulants and/or sedatives.

Rationale for sample size and statistical power

Statistical power and sample size calculations were conducted using G*Power software²⁶,²⁸ and are based on the estimated effect size of the hypothesised difference on the primary outcome between the two study arms: SDI vs HDI. A sample size of 180 participants per group is required to ensure 80% statistical power at the 2-sided 0.05 significance level to detect a between-group difference in the proportion of participants engaged in OUD continuation treatment within 10 days after randomisation with the estimated effect size w=0.16³⁷ and taking into account a potential loss to follow-up of 15% of the enrolled participants. This sample size will also provide 80% or greater statistical power to detect a small to medium magnitude difference effect size d=0.30 or larger,³⁸ on outcomes of opioid craving, withdrawal symptoms and illicit drug use assessed for 10 days post randomisation between the two study arms. The planned study sample and the proposed analytical methods will also allow for meaningful exploratory evaluations of potential differential effects of sex, race, ethnicity, insurance types and housing stability on the evaluated treatment outcomes.

Missing data and dropouts

The primary outcome measure (the proportion of patients participating in OUD treatment within 10 days post randomisation) will be based on validated OUD treatment provider documentation. Patients who are lost to follow-up or for whom verifiable documentation of treatment participation is not available for any reason will be coded as not participating in OUD treatment. No imputation of missing data will be performed for any analyses.

Data safety and monitoring board

An independent NIDA CTN DSMB will examine accumulating data to assure protection of participants’ safety during the active study protocol. The CTN DSMB is responsible for conducting periodic reviews of accumulating safety and efficacy data as defined in the protocol or as required based on emerging trends that impact participant safety and need to make the most informed recommendations. The DSMB will provide recommendation(s) to NIDA that will be used to determine whether there is support for continuation of the trial as originally designed, if the trial should be modified or if the trial should be halted, for reasons relating to the safety of the study participants, the efficacy of the treatment under study or inadequate trial performance (eg, poor recruitment).

Confidentiality

Participant records will be held confidential by using study codes for identifying participants, secure storage of any documents that have participant identifiers and secure computing procedures for entering and transferring electronic data. The study participant’s contact information will be securely stored at each clinical site for internal use during the study and will be securely deleted after the required designated period following trial completion.

Ethics and dissemination

This study has been reviewed and approved by the WCG institutional review board, with protocol version 1.0 submitted in June 2024 (WCG # 20242480) and approved in September 2024. Any relevant modifications in protocol will be submitted to the WCG IRB as amendments. This study was registered (clinicaltrials.gov https://clinicaltrials.gov/study/NCT06494904) on 2 July 2024. Study findings will be widely disseminated through Open Access publications and presentations at national and international emergency medicine and addiction conferences.

Patient and public involvement

Patients and the general public were not involved in the design and conduct of this clinical trial, although the planning of this trial has been informed by qualitative research with ED patients with OUD focused on the initiation of treatment for OUD in the ED.