Symptom-Inhibited Naloxone Induction (SINI) for Buprenorphine Initiation: A Feasibility Trial

Phase 4Not Yet RecruitingNCT07439549

Pouya Azar12 enrolled

Overview

The goal of this clinical study is to evaluate a new treatment approach called symptom inhibited naloxone induction (SINI) for people with opioid use disorder. In this study, participants will receive small doses of intravenous (IV) naloxone at intervals until they feel mild opioid withdrawal symptoms. At this point, they will be given buprenorphine/naloxone under the tongue to help with the withdrawal symptoms. One hour after, they will receive a injection of long acting buprenorphine under the skin if they choose to. The main questions this study aims to answer are: Is it feasible to use the SINI protocol in inpatient and outpatient settings? Is the SINI protocol safe and tolerable for individuals with opioid use disorder?

This is a prospective, single arm, open label, feasibility study involving 12 participants with opioid use disorder who have a clinical indication to start opioid agonist therapy with buprenorphine. Eligible participants provide informed consent will undergo buprenorphine induction using the symptom inhibited naloxone induction protocol (SINI). A study doctor or nurse will administer 0.1 - 0.2 mg of intravenous naloxone every 2 minutes until the patient is in mild opioid withdrawal, defined as a Clinical Opiate Withdrawal Scale (COWS) score of ≥8 and at least two objective withdrawal signs not attributable to other causes. Once this is level of opioid withdrawal is achieved, ≥ 8 mg of sublingual buprenorphine/naloxone (BUP/NLX) will be administered consistent with the recommended minimum induction dose in the product monograph and published high dose induction strategies. If the patient opts for extended release buprenorphine treatment (BUP-XR) and their COWS score has not increased by more than 5 points one hour after sublingual buprenorphine/naloxone administration, a 300 mg dose of BUP-XR will be administered subcutaneously one hour after their sublingual BUP/NLX. The following information will the collected * Substance use history * Substance use treatment utilization * Harm reduction service utilization * Clinical Opiate Withdrawal Scores / Subjective Opiate Withdrawal Scores * Vital Signs (Heart rate, blood pressure, respiratory rate, oxygen saturation) * Adverse events * Treatment satisfaction questionnaire for medication (TSQM) Following the SINI protocol, participants receiving sublingual BUP/NLX treatment, ongoing medication dispensing will transition to a community pharmacy in accordance with standard clinical practice. Participants receiving subcutaneous BUP/XR treatment, subsequent doses will be administered either at a CPAS physician's office, clinic, or pharmacy, as per standard clinical practice. Participants will be followed for 28 days, during which the information listed below will be collected. * Retention on BUP/NLX or BUP-XR, or other forms of OAT * Unregulated opioid use * Rates of overdose and hospitalization * Adverse events

Interventions

Naloxone Hydrochloride 0.4 MG/MLDRUG

0.1 mg naloxone is administered IV every 2 minutes until mild symptoms with COWS ≥ 8 and at least two objective withdrawal signs not attributable to other causes. If fourth and subsequent doses are needed, and withdrawal symptoms are not emerging or are progressing too slowly, the dose may be increased to 0.2 mg based on clinical judgment.

Buprenorphine hydrochloride and naloxone hydrochloride dihydrate sublingual tablet (2 mg/0.5 mg and 8 mg/2 mg)DRUG

If the patient opts for BUP/NLX treatment, ≥ 2 mg BUP/NX will be administered under the tongue Q1-3H PRN for withdrawal/pain/cravings. The total dose administered on the first day determines the starting dose for Day 2. If symptoms persist on Day 2, extra doses can be given until stable, and that total amount on Day 2 becomes the new maintenance dose (Maximum dose: 32 mg/day).

Buprenorphine extended-release injection (300 mg/1.5 mL)DRUG

If the patient opts for BUP-XR, 1 hour after the administration of sublingual buprenorphine/naloxone, study nurse or physician will subcutaneously administer buprenorphine extended-release injection (300 mg/1.5 mL).

Eligibility

Sex: ALLMin age: 19 Years

Medical Language ↔ Plain English

Inclusion Criteria: To be eligible for this study, participants must fulfill all the following inclusion criteria: * 19 years of age or older. * Opioid use disorder as confirmed by DSM 5 diagnostic criteria. * Clinical indication to start OAT with buprenorphine. * Willingness to tolerate mild opioid withdrawal precipitated by naloxone, expected to last less than 20 minutes. * Willing and able to have and maintain IV access for the duration of the SINI * If of childbearing potential and elected BUP-XR, agree to use an effective method of birth control. o Highly effective methods of birth control include hormonal contraceptives (e.g., combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device (IUD) or intrauterine system (IUS); vasectomy and tubal ligation. Effective methods include barrier methods of contraception (e.g., male condom, female condom, cervical cap, diaphragm, contraceptive sponge). * Willing and able to provide written informed consent for study participation. Exclusion Criteria: If participants meet any of the following exclusion criteria, they will be excluded from participation in the study: * Diagnosis of severe medical or psychiatric conditions contraindicated for naloxone or buprenorphine. * Concomitant use of medications with drug-drug interactions with buprenorphine, unless alternative treatment options are less appropriate and a risk-benefit assessment has been discussed and recommended by the participant's healthcare team. o Examples include, but are not limited to: benzodiazepines and non-benzodiazepine central nervous system depressants, naltrexone, CYP3A4 inhibitors and inducers, serotonergic drugs, monoamine oxidase inhibitors, QTc interval-prolonging drugs, diuretics, anticholinergics, and antiretrovirals. * Known allergy or sensitivity to naloxone or buprenorphine. * Use of BUP/NLX within the past 9 days. * Use of BUP-XR within the past 43 weeks. * Previous participation in this study (previous receipt of SINI in a clinical setting is not exclusionary). * Currently pregnant or breastfeeding. * COWS ≥ 8

Outcomes

Primary Outcomes

Enrollment rate

Number of participants enrolled per month

Time frame: Enrollment

Proportion of ≥8 mg BUP/NLX

Proportion of enrolled patients who receive ≥8 mg sublingual buprenorphine/naloxone within 1 hour of protocol initiation

Time frame: Within 1 hour of first NLX dose

Proportion of 300 mg BUP-XR

Proportion of enrolled patients who transition to 300 mg Buprenorphine extended release within 1 hour of first BUP/NLX dose, for those who elect it

Time frame: Within 1 hour of first BUP/NLX dose

Secondary Outcomes

Recruitment

Number of patients approached, eligible, consented

Time frame: Through study completion, anticipated to be 6 months

Unregulated opioid use

Opioid use within 24 hours prior to SINI, during the induction, OAT, and follow up

Time frame: Baseline, Follow up (Day 14 and 28).

Severity of Opioid Withdrawal (Subjective)

Subjective Opiate Withdrawal Scale (Score range: 1-30) Mild Withdrawal: 1 - 10 , Moderate withdrawal: 11 - 20 , Severe withdrawal: 21 - 30

Time frame: Intervention (before, after, and during), and follow up (Day 14 and 28)

Respiratory rate

Respiration rate

Time frame: Baseline; 2 minutes after each NLX dose; immediately prior to first BUP/NLX dose; 1 hour and 3 hours after first BUP/NLX dose; immediately prior to 300 mg BUP-XR dose; 1 hour, 12 hours, and 24 hours after 300 mg BUP-XR dose

Heart Rate

Heart rate

Oxygen Saturation

Oxygen saturation

Blood Pressure

Systolic and Diastolic Blood Pressure

Participant reported experience

Treatment Satisfaction Questionnaire for Medication (TSQM).

Time frame: Post intervention and follow up (Day 14 and 28)

Adverse Event

Incidence of adverse events (AEs) possibly/probably/definitely related to the study drug

Time frame: During intervention and follow up (Day 14 -28)

Severity of Opioid Withdrawal (Objective)

Clinical Opiate Withdrawal Score (Score: 0-40) 0-12: Mild withdrawal, 13-24: Moderate withdrawal, 25-36: Moderately severe withdrawal, and above 36: Severe withdrawal

Time frame: Intervention (before, after, and during), and follow up (Day 14 and 28)

Intervention delivery and timing

Dose and timing of each NLX dose, the first BUP/NLX dose, any subsequent BUP/NLX doses prior to 300 mg BUP-XR, and the 300 mg BUP-XR dose (for patients who elect it)

Time frame: From first NLX administration through 24 hours after 300 mg BUP-XR administration, or through 3 hours after first BUP/NLX administration for participants not receiving BUP-XR.

OAT retention

Retention of sublingual buprenorphine/naloxone, extended release buprenorphine, and other opioid agonist therapy

Time frame: Follow up (Day 14 and 28)

Overdose and Hospitalization

Rate of overdose and hospitalization

Time frame: Follow up (Day 14 to Day 28)