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

Official title

Symptom-inhibited Naloxone Induction (SINI) to Initiate Buprenorphine/Naloxone and Buprenorphine Extended-release for Opioid Use Disorder: A Single-arm Feasibility Trial

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?

Detailed description

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

• Drug Naloxone Hydrochloride 0.4 MG/ML
  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.
• Drug Buprenorphine hydrochloride and naloxone hydrochloride dihydrate sublingual tablet (2 mg/0.5 mg and 8 mg/2 mg)
  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).
• Drug Buprenorphine extended-release injection (300 mg/1.5 mL)
  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).

Primary outcome measures

• Enrollment rate [Time frame: Enrollment]
• Proportion of ≥8 mg BUP/NLX [Time frame: Within 1 hour of first NLX dose]
• Proportion of 300 mg BUP-XR [Time frame: Within 1 hour of first BUP/NLX dose]

Secondary outcome measures (12)

• Recruitment [Time frame: Through study completion, anticipated to be 6 months]
• Unregulated opioid use [Time frame: Baseline, Follow up (Day 14 and 28).]
• Severity of Opioid Withdrawal (Subjective) [Time frame: Intervention (before, after, and during), and follow up (Day 14 and 28)]
• Respiratory 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 [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]
• Oxygen Saturation [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]
• Blood Pressure [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]
• Participant reported experience [Time frame: Post intervention and follow up (Day 14 and 28)]
• Adverse Event [Time frame: During intervention and follow up (Day 14 -28)]
• Severity of Opioid Withdrawal (Objective) [Time frame: Intervention (before, after, and during), and follow up (Day 14 and 28)]
• Intervention delivery and timing [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 [Time frame: Follow up (Day 14 and 28)]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Canada · 2 centers

• Hope to Health Research & Innovation Centre — Vancouver
• Vancouver General Hospital — Vancouver

Identifiers

NCT: NCT07439549 · H25-01585

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗