Buprenorphine Loading in the Emergency Department

Study Overview
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Brief Summary
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Buprenorphine (BUP) is FDA-approved for the treatment of opioid withdrawal and opioid use disorder. Few ED providers have received the necessary DEA registration (aka X waiver) required to prescribe BUP, and urgent appointments to continue ongoing BUP treatment may not be readily available, thus leading to medication discontinuity. A loading dose induction strategy with 32mg of BUP may help effectively link ED patients to outpatient treatment while minimizing known barriers to ED uptake. Administering a loading dose of BUP to saturate mu-opioid receptors would extend the duration of action and provide additional time to secure ongoing treatment. Further, BUP's ceiling effect on respiratory depression makes it a remarkably safe drug even at high doses. In recent years, ED providers have begun to incorporate this approach into clinical protocols, however, it has not been formally studied in this clinical setting. The investigator's study represents the necessary step of studying this novel approach in the ED setting to define the parameters for clinical protocols and large-scale studies.

Detailed Description
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A novel induction strategy, in which a loading dose of Buprenorphine (BUP) 32mg is administered, has the potential to mitigate barriers to treatment initiation. ED providers can treat patients with BUP for opioid withdrawal since DEA registration (X-waiver) is not required unless they wish to issue a prescription. Current BUP induction protocols, developed for inpatient and ambulatory care settings as well as for unobserved self- administration via prescription, usually recommend a first day dose of 8mg given in divided doses of 2- 4mg. However, patients discharged with ≤ 8mg SL total dose may experience return of withdrawal symptoms and/or opioid craving within only 4 hours.Treatment with a loading dose of 32mg in the ED may provide the necessary bridge treatment, relieving symptoms of withdrawal until a patient is able to attend a follow up appointment for further treatment.

Official Title
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Buprenorphine Loading in the Emergency Department

Conditions
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Opioid-use Disorder

Intervention / Treatment
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* Drug: Buprenorphine Naloxone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study. Meets DSM-5 criteria for moderate to severe OUD Has a positive urine screen for opioids and a negative urine screen for methadone Must be experiencing opioid withdrawal with a COWS score ≥8 Is willing and able to participate in the study and follow study procedures Is able to provide adequate and reliable locator information for follow-up Has reliable access to a phone Exclusion Criteria: Is currently engaged in medication treatment for OUD with methadone, BUP, or naltrexone Has a urine toxicology test that is positive for methadone or buprenorphine Currently requires prescribed opioids for treatment of an ongoing pain condition Has a known allergy to BUP Is pregnant as determined by urine hCG testing at the index ED visit Is breastfeeding as determined by self-report Has medical, psychiatric, or concurrent substance use conditions or severe cognitive impairment which might prelude safe participation Is a prisoner or in police custody at the time of the index ED visit Has previously enrolled in the current study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BUP treatment arm<br>Subjects will be given BUP 32mg in 2 doses, and observed for at least 90 minutes after the 2nd dose. The whole process will take a total of about 3-4 hours including the consenting process. Subjects will be asked questions and be examined repeatedly. Subjects will have 4 in-person visits and a phone call in addition to review of medical records. | Drug: Buprenorphine Naloxone<br>* Participants will receive the BUP SL 32mg in divided doses rather than all at once. If after the initial 8mg dose a participant experiences over-sedation or another adverse event that would preclude further dosing, such as an allergic reaction, the subsequent dose will not be administered and the patient will be withdrawn from the study. The participant will be reassessed for other possible etiologies for these symptoms.<br>* Other names: Suboxone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with successful rapid induction | This will be measured by the proportion of participants who report Successful Rapid Induction. Participants will receive a loading dose of BUP SL 32mg in the ED without experiencing a clinically significant serious and/or severe adverse event (AE) related to the intervention - specifically, the receipt of a dose of BUP SL greater than 8mg during the Index ED visit. Successful rapid induction is defined only by the outcome of the participant's visit, and not by any following research visits. | Day 0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in opioid withdrawal and craving using COWS | The Clinical Opiate Withdrawal Scale (COWS) is an 11-item scale designed to be administered by a clinician. The tool can be used in both inpatient and outpatient settings to reproducibly rate common signs and symptoms of withdrawal and monitor these symptoms over time. The summed score can be used to help clinicians determine the stage or severity of withdrawal and assess the level of physical dependence on opioids. The change in withdrawal and craving symptoms will be measured using COWS during the index visit, as well as during the research visits on days 1, 2, and 3. | Index ED Visit 1(Day 0), Research Visit 2 ( Day 1), Research Visit 3 (Day 2), Research Visit 4 (Day 3)] | 
| Change in Opioid withdrawal and craving scores using SOWS during the index ED visit | The Subjective Opiate Withdrawal Scale (SOWS) is a self-administered scale for grading opioid withdrawal symptoms. It contains 16 symptoms whose intensity the patient rates on a scale of 0 (not at all) to 4 (extremely). Similar to COWS, the score is used to assess stage and severity of withdrawal and level of physical dependence on opioids. SOWS will be assessed during the index visit, as well as research visits on days 1, 2, and 3. | Index ED Visit 1(Day 0), Research Visit 2 ( Day 1), Research Visit 3 (Day 2), Research Visit 4 (Day 3)] | 
| Change in Time to next BUP dose (length of withdrawal suppression) | Participants will asked to report the date and time of the next dose of BUP following the loading dose given during their index visit. If needed for treatment of withdrawal, this dose may be administered or prescribed by the study team during a research visit. | Research Visit 2 ( Day 1), Research Visit 3 (Day 2), Research Visit 4 (Day 3), Research phone call (Day 30) | 
| Change in the Opioid and other illicit drug use | Participants will be asked to report any use of opioids as well as other illicit drugs during the study period. Usage patterns of opioids and other substances will be compared from before and after administration of the 32 mg loading dose of BUP. Substance use will be reported at each research visit, as well as during the 30 day follow up phone call. During the phone call, the Timeline Follow-Back method (TLFB) will be used to report usage during the past 30 days. | Research Visit 2 ( Day 1), Research Visit 3 (Day 2), Research Visit 4 (Day 3), Research phone call (Day 30) | 
| Change in healthcare utilization | Change in healthcare utilization using the non-study treatment service use form, participant satisfaction and perceived utility of ED-initiated intervention. Engagement in treatment will be assessed by self-report and/or confirmed by treatment provider. | Research Visit 2 ( Day 1), Research Visit 3 (Day 2), Research Visit 4 (Day 3), Research phone call (Day 30) |