Randomized Trial of Buprenorphine Microdose Inductions During Hospitalization

Study Overview
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Brief Summary
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Investigators will test a novel protocol for starting BUP (buprenorphine-naloxone) treatment. The BUP microdose induction protocol has participants start very low doses of BUP without stopping other opioids that they are taking. The treatment as usual (TAU) has participants stop other opioids and experience opioid withdrawal before starting BUP. Investigators propose to test BUP microdose inductions vs. TAU in a randomized controlled trial.

Detailed Description
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Investigators will conduct a hybrid type 1 effectiveness-implementation study, using a pragmatic, open-label, randomized controlled trial (RCT). Investigators will randomize 270 hospitalized patients with (a) chronic pain and (b) opioid misuse or opioid use disorder (OUD) to a 5-day BUP microdose induction protocol (without stopping full agonists) or 2-day standard induction (with stopping full agonists), and then link participants to outpatient BUP treatment when they are released from the hospital. Study assessment visits will occur at baseline, 1 week, and 1, 3, and 6 months. Assessments will include interviews and urine drug tests to determine whether participants start BUP, continue BUP, have improvements in pain and decrease illicit opioid use. During induction and 3-months of follow-up, investigators will also collect data on mobile devices to assess opioid withdrawal, opioid craving, pain, and anxiety. These data will allow investigators to assess whether BUP microdosing targets of engagement-opioid- and pain-related symptoms-mediate OUD outcomes. Exploratory analyses will also examine pain as a trigger for opioid relapse. Aim 1: To test the effectiveness of BUP microdose induction (vs. TAU) on OUD outcomes. H1: The microdose arm (vs. TAU) will have better BUP treatment uptake and retention, and less illicit opioid use. H2: Improvements in H1 will be mediated by opioid- and pain-related symptoms. Aim 2: To test the effectiveness of microdosing (vs. TAU) on pain outcomes. H3: The microdose arm (vs. TAU) will have less pain intensity and interference, and improved quality of life. H4: Improvements in H3 will be mediated by OUD outcomes. Aim 3: To inform future implementation and dissemination efforts, investigators will: 3a) Examine factors influencing reach, adoption, implementation, and maintenance of BUP microdosing. Investigators will use qualitative and quantitative methods to describe multi-level factors influencing these domains; 3b) Calculate the cost and examine cost-effectiveness of BUP microdosing. H5: Compared with TAU, BUP microdosing will be cost-effective from a societal and a health sector perspective.

Official Title
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Randomized Trial of Buprenorphine Microdose Inductions During Hospitalization

Conditions
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Substance Use Disorders, Opioid-use Disorder, Chronic Pain

Intervention / Treatment
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* Drug: BUP microdose induction
* Drug: TAU
* Behavioral: Linkage to outpatient BUP treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Opioid misuse or OUD Chronic pain Currently taking opioids Fluency in English or Spanish Planned hospitalization for ≥ 48 hours Exclusion Criteria: Current OUD treatment (BUP, methadone, naltrexone) Severe alcohol or benzodiazepine use disorder Hypersensitivity to BUP or naloxone Pain due to malignancy Severe untreated mental illness (suicidality, psychosis) Pregnancy Unable to consent due to pain or cognitive impairment

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BUP microdose induction<br>Participants in this arm will receive a novel BUP microdose induction protocol. | Drug: BUP microdose induction<br>* Participants will be started on a 5-day BUP microdose induction protocol (without stopping full agonists). Day 1: participants will receive buprenorphine (Belbuca) 225 mcg mg every 12 hours Day 2: participants will receive buprenorphine (Belbuca) 450 mcg every 8 hours Day 3: participants will receive buprenorphine-naloxone 2-0.5 mg every 8 hours Day 4: participants will receive buprenorphine-naloxone 4-1 mg every 8 hours Day 5: participants will receive buprenorphine-naloxone 8-2 mg every 12 hours<br>Behavioral: Linkage to outpatient BUP treatment<br>* Participants will be given an expedited appointment (within 2 weeks) to continue BUP treatment at a Montefiore community health center<br>|
| Active Comparator: Treatment As Usual (TAU)<br>Participants in this arm will receive standard BUP induction protocol. | Drug: TAU<br>* 2-day standard BUP induction protocol (with stopping full agonists) Day 1: hold all opioids Day 2: buprenorphine-naloxone 2-0.5 mg every 6 hours Day 3: buprenorphine-naloxone 8-2 mg every 12 hours<br>Behavioral: Linkage to outpatient BUP treatment<br>* Participants will be given an expedited appointment (within 2 weeks) to continue BUP treatment at a Montefiore community health center<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BUP treatment uptake | The percentage of participants who start BUP treatment, defined as receiving BUP 7 days after the baseline visit, will be reported for each arm. | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Illicit opioid use | The mean number of days of illicit opioid use, defined as self-reported use of heroin, fentanyl, or non-prescribed opioid analgesics in the prior 30 days based on the Addiction Severity Index, will be reported for each arm. | 1, 3, and 6 months | 
| BUP retention in care | The percentage of participants who are retained in BUP treatment, defined as having a BUP prescription written 180-210 days (6-month retention) after enrollment, will be reported for each arm. | 6 months |