Slow-Release Oral Morphine for the Treatment of Opioid Use Disorder (pRESTO)

M. Eugenia Socias

Status and phase: Terminated; Phase 3

Conditions: Morphine; Fentanyl; Opioid-Related Disorders; Methadone; Opiate Substitution Treatment

Treatments: Drug: Slow release oral morphine (SROM); Drug: Methadone

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03948464

BCCSU-002

Details and patient eligibility

About

This is a non-inferiority randomized clinical trial that will compare slow release oral morphine vs methadone as a second line oral treatment for opioid use disorder.

Full description

Slow-release oral morphine (SROM) has emerged as a promising yet understudied form of oral treatment for opioid use disorder (OUD), with preliminary studies suggesting similar efficacy rates as methadone with respect to promoting abstinence, and with better improvements in a number of patient-reported outcomes, including tolerability, treatment satisfaction, mental symptoms, and craving. The proposed study is an open-label, non-inferiority, randomized controlled trial evaluating the relative effectiveness, safety and acceptability of SROM vs. methadone for the treatment of OUD in outpatient clinical settings. Participants will be randomized 1:1 to SROM or methadone for 24 weeks. Data linkages performed three years after randomization will evaluate long term health outcomes. This study aims to provide evidence to optimize care for individuals with OUD, and potentially increase access to additional form of evidence-based oral treatment.

Enrollment: 27 patients

Sex: All

Ages: 19 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Participants must meet all the following criteria to be eligible for the study:

1. Be between 19 and 65 years of age, inclusively;

2. Be diagnosed with opioid use disorder requiring opioid agonist treatment (OAT), as per DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) criteria and the discretion of the study physician;

3. Be interested in receiving OAT;

4. Be willing and eligible to be randomized to slow release oral morphine (SROM) or methadone-based OAT as per British Columbia guidelines;

5. If female:

   1. Be of non-childbearing potential, defined as (i) postmenopausal (12 months of spontaneous amenorrhea and over 45 years of age); or (ii) documented surgical sterilization (i.e., tubal ligation, hysterectomy, or bilateral oophorectomy); or
   2. If of childbearing potential, be willing to use an acceptable method of contraception throughout the study and have a negative pregnancy test at screening;

6. Be able to provide written informed consent;

7. Be willing to comply with study procedures;

8. Be able to communicate in English;

Exclusion criteria

Participants will be excluded from the study if any of the following criteria are met:

1. Any disabling, severe, or unstable medical or psychiatric condition that, in the opinion of the study physician, precludes safe participation in the study or the ability to provide fully informed consent, as assessed by medical and psychiatric history, physical examination, vital signs, and/or laboratory tests. These may include but are not limited to: significant respiratory depression, severe respiratory compromise or obstructive disease, severe respiratory distress, acute or severe bronchial asthma, known or suspected paralytic ileus;
2. Any severe or unstable co-morbid substance use disorder (e.g., delirium tremens, acute alcohol intoxication) that, in the opinion of the study physician, precludes safe participation in the study;
3. Maintenance on buprenorphine at doses of ≥4 mg in the 5 days prior to screening and stable in the opinion of the study physician;
4. Maintenance on methadone at doses of ≥60 mg in the 5 days prior to screening and stable in the opinion of the study physician;
5. Maintenance on slow release oral morphine at doses of ≥250 mg in the 5 days prior to screening and stable in the opinion of the study physician;
6. Pregnant, breastfeeding, or planning to become pregnant during the study period;
7. History of a serious adverse drug reaction, hypersensitivity reaction, or allergy to methadone or SROM;
8. Use of an investigational drug in the 30 days prior to screening;
9. Pending legal action or other reasons that might prevent completion of the study;
10. Current or anticipated need for treatment with any medication that may interact with methadone or SROM (e.g., benzodiazepines, monoamine oxidase inhibitors [MAOIs] pRESTO Protocol Version 3.0, 08 October 2019 Page 21 of 66 used currently or within the past 14 days) and that, in the opinion of the study physician, would be deemed unsafe or could prevent study completion.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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27 participants in 2 patient groups

Slow release oral morphine (SROM)

Experimental group

Description:

Daily witnessed ingestion of SROM (24-hour formulation) for 24 weeks as per provincial and national guidelines for opioid use disorder.

Treatment:

Drug: Slow release oral morphine (SROM)

Methadone

Active Comparator group

Description:

Daily witnessed ingestion of methadone for 24 weeks as per provincial and national guidelines for opioid use disorder.

Treatment:

Drug: Methadone