This is an open-label, single arm, prospective clinical trial involving 50 individuals
with opioid use disorder (OUD) who use illicit fentanyl and for whom opioid agonist
therapy (OAT) with either methadone or slow-release oral morphine (SROM) is clinically
indicated. Participants who provide informed consent and are found to be eligible will
undergo a "symptom-inhibited" fentanyl induction procedure under close medical
supervision in a community clinic. A study doctor or nurse will administer intravenous
(IV) fentanyl at 5-minute intervals until the participant indicates comfort and their
opioid withdrawal symptoms are minimized, or until their sedation level is 2 on the
Pasero Opioid-induced Sedation Scale (POSS). Immediately before the first dose of
fentanyl, after each dose during the induction procedure, and every 5 minutes for 15
minutes (or until stable) after the final fentanyl dose, study staff will monitor the
participants' level of sedation (POSS), withdrawal symptoms (Clinical Opiate Withdrawal
Scale, COWS), and vital signs (heart rate, respiratory rate, blood pressure, oxygen
saturation).
Selection of the appropriate OAT agent for each participant will be done in advance by
the clinical addictions management team. Participants with a QTc interval >500 msec on
screening ECG will not be eligible to receive methadone, and will be offered SROM if
clinically appropriate. Participants with known chronic kidney disease will have serum
creatinine tested for calculation of estimated glomerular filtration rate (eGFR) if they
are to receive SROM; if eGFR is between 15 and 60 mL/min, SROM doses will be adjusted
according to current recommendations [Lexicomp 2021]; if eGFR<15 mL/min, the participant
will not be eligible to receive SROM.
The total cumulative dose of IV fentanyl administered during the induction phase (the
loading dose) x 8 will be used as a proxy for the individual's 24-hour opioid tolerance,
which in turn will be converted to oral morphine equivalents and used to calculate the
appropriate starting dose of methadone or SROM, up to a maximum daily dose of 200 mg for
methadone or 2000 mg for SROM. The first OAT dose will be administered under observation
in the clinic, preferably on the same day and 15-30 minutes after the completion of the
induction procedure. Participants will remain in the clinic under observation for 3 hours
after the first dose of methadone or SROM. Vital signs, POSS, and COWS will be monitored
before the first OAT dose, then hourly and prior to discharge. Study staff will assess
the participants' satisfaction with the symptom-inhibited fentanyl induction process,
using the single item Medication Satisfaction Questionnaire (MSQ) and 3-open ended
questions. Participants will be discharged from the clinic when medically stable.
Participants will return to the study clinic once daily for 7 days for OAT dispensing and
assessment of activity level in the previous 24 hours, vital signs, POSS, and COWS. An
ECG will be performed on OAT Days 3 (+/- 2 days) and 7 (+/- 2 days) for participants
receiving methadone. Methadone will be preferentially be maintained at the same dose for
the first 7 days; however, methadone dose may be adjusted (up to a maximum daily dose of
200 mg) if felt to be safe and clinically indicated. SROM doses may be increased by 100
mg every 24-48 hours (consistent with current clinical guidelines from the British
Columbia Centre on Substance Use) up to a maximum daily dose of 2000 mg if clinically
indicated (presence of cravings or withdrawal symptoms, and absence of SROM-related
adverse events and opioid toxicity).
After Day 7, OAT will be dispensed through a community pharmacy according to standard
procedure. Participants will return to the study clinic for the following assessments at
7 days (up to +2 days) , 1 month (+/- 2 weeks), 3 months (+/- 1 month), 6 months (+/- 2
months), and 12 months (+/- 3 months) post-induction:
Participant satisfaction with their current OUD treatment (single-item MSQ)
Whether maintained on oral OAT and, if so, current dose
Whether on prescribed opioids for risk mitigation, and if so, type and dose
Self-reported illicit opioid use - type, route, amount, frequency
Self-reported use of other substances - type, route, amount, frequency
Withdrawal symptoms (COWS score)
Urine drug test
At the same time points, additional information will be obtained from the clinic's
electronic medical record (EMR) database:
Overdose events requiring intervention (acute care or hospitalization)
Hospitalizations, including diagnosis, route of admission, dates, duration
Survival; if deceased, cause of death