Chronic Pain, Opioid-use Disorder, Substance Use Disorders
Conditions
Brief summary
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
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.
Interventions
DRUGBUP microdose induction
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
DRUGTAU
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
BEHAVIORALLinkage to outpatient BUP treatment
Participants will be given an expedited appointment (within 2 weeks) to continue BUP treatment at a Montefiore community health center
Sponsors
Montefiore Medical Center
National Institute on Drug Abuse (NIDA)
Weill Medical College of Cornell University
Wake Forest University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BUP Treatment Uptake | 7 days | The percentage of participants who start BUP treatment, defined as receiving BUP 7 days after the baseline visit, will be reported for each arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity | 3 months | Mean pain intensity score, measured using the Brief Pain Inventory (BPI), will be reported for each study arm. The pain intensity score has 4 items that are each rated on a scale from 0 (low intensity) to 10 (high intensity). The score reported is the average score from the 4-items also reported on a scale of 0-10. |
| Pain Interference | 3 months | Mean pain interference score, measured using the pain interference scale from the BPI, which is a 7-item instrument measuring the impact of pain on daily activities and physical functioning, will be reported for each study arm. Each item is rated on a scale from 0 (low interference) to 10 (high interference). The score reported is the average score from the 7-items also reported on a scale of 0-10. |
| BUP Retention in Care | 1, 3, and 6 months | The number/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. |
| Illicit Opioid Use | 1, 3, and 6 months | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAaron Fox, MD
Montefiore Medical Center
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BUP Microdose Induction Participants in this arm will receive a novel BUP microdose induction protocol.
BUP microdose induction: 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
Linkage to outpatient BUP treatment: Participants will be given an expedited appointment (within 2 weeks) to continue BUP treatment at a Montefiore community health center | 12 |
| Treatment As Usual (TAU) Participants in this arm will receive standard BUP induction protocol.
TAU: 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
Linkage to outpatient BUP treatment: Participants will be given an expedited appointment (within 2 weeks) to continue BUP treatment at a Montefiore community health center | 11 |
| Total | 23 |
Baseline characteristics
| Characteristic | Total | Treatment As Usual (TAU) | BUP Microdose Induction |
|---|---|---|---|
| Age, Continuous | 47.3 years STANDARD_DEVIATION 15.8 | 49.4 years STANDARD_DEVIATION 15.4 | 45.4 years STANDARD_DEVIATION 16.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 5 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 6 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Opioid Use Disorder status Opioid use disorder mild or Opioid misuse | 14 Participants | 7 Participants | 7 Participants |
| Opioid Use Disorder status Opioid use disorder moderate or severe | 9 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 8 Participants | 4 Participants | 4 Participants |
| Sex: Female, Male Female | 9 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 14 Participants | 8 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 1 / 11 |
| other Total, other adverse events | 12 / 12 | 11 / 11 |
| serious Total, serious adverse events | 8 / 12 | 6 / 11 |
Outcome results
Primary
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.
Time frame: 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BUP Microdose Induction | BUP Treatment Uptake | 11 Participants |
| Treatment As Usual (TAU) | BUP Treatment Uptake | 10 Participants |
p-value: 195% CI: [0.05, 16.54]Fisher Exact
Secondary
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.
Time frame: 1, 3, and 6 months
Secondary
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.
Time frame: 1, 3, and 6 months
Secondary
Pain Intensity
Mean pain intensity score, measured using the Brief Pain Inventory (BPI), will be reported for each study arm.
Time frame: 3 months
Secondary
Pain Interference
Mean pain interference score, measured using the pain interference scale from the BPI, which is a 7-item instrument measuring the impact of pain on daily activities and physical functioning, will be reported for each study arm.
Time frame: 3 months