Opioid Use DisorderPhase 4NCT07546396
Methadone Rapid Restart
A Phase 4 study testing Methadone in people with Opioid Use Disorder, run by Pouya Azar at 1 site in Canada.
Trial summary
The usual treatment for opioid use disorder (OUD) is opioid agonist therapy (OAT) with either methadone or buprenorphine. These treatments are well-established, reduce the risk of fatal overdoses, and are considered the standard approach. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Opioid Use Disorder
- What is being tested?
- Methadone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteCanada
- Study dates
- May 2026to Mar 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 19 years or older
- Opioid use disorder (OUD) of any severity by DSM-5 TR Clinical Diagnostic criteria [American Psychiatric Association, 2022]
- Previously 'stable' on methadone as per the below definitions:
- Previous maintenance treatment with methadone for opioid use disorder at a stable dose for at least 5 consecutive days prior to discontinuing, with allowance for a maximum of 1 missed dose within that 5-day period.
- Participants who were being titrated on methadone for opioid use disorder prior to discontinuation. If participants were on the most recent dose for less than 5 days, they can be restarted on the prior dose providing they cumulatively received 5 consecutive doses (with a maximum of 1 missed dose in that period) between the two most recent dosages.
- Missed 4-8 doses of methadone in a row leading up to intake assessment.
Show all 18Show fewer
- Participant able to provide baseline opiate use history as per opiate use screening questions in Appendix A. This must provide an estimate of opiate use prior to stopping methadone and change in use since stopping.
- Self-reported increased use of fentanyl since stopping methadone.
- No significant change in opiate withdrawal symptoms as compared to when on methadone, based on self-report and examination.
- Urine drug test (UDT) positive for fentanyl at screening or within 24 hours prior to re-initiating methadone.
- Participant wishes to continue methadone maintenance treatment.
- If applicable the participant must be willing to complete a urine pregnancy test to ensure they are not currently pregnant.
- Participants will require a baseline ECG that demonstrates a QTc < 500ms.
- For participants from VGH study site specifically:
- must be admitted to either psychiatry or CTU, ideally with planned admission of at least 3 days.
- must agree if discharged prior to the completion of the 7 day follow up period, to either return to VGH Diamond Centre for follow up assessments on Days 1/3/7 (+/-2 days).
- must have access to a functioning cell phone to allow for the study team to contact them in case of discharge prior to completion of study follow up period.
- The participants must be willing and able to provide written informed consent for study participation.
Who cannot join
- COWS score of 8 or more at the time of clinician assessment
- Self-reported Opioid overdose or naloxone administration since methadone discontinuation or during the 5 days prior to methadone discontinuation
- Self-reported New cardiac disease diagnosis since methadone discontinuation
- Self-reported Intolerable side effects reported when taking methadone
- Individuals who are pregnant (urine pregnancy test) or breast-feeding (self-reported)
- Use of buprenorphine-naloxone (Suboxone®, Sublocade®, Butrans ®) within the previous 3 days (self-reported)
- Participants with a QTc interval >500 msec on the screening ECG
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Methadone Rapid Restart Study
The usual treatment for opioid use disorder (OUD) is opioid agonist therapy (OAT) with either methadone or buprenorphine. These treatments are well-established, reduce the risk of fatal overdoses, and are considered the standard approach. However, current methadone guidelines were developed when most people were using heroin, which is far less potent than today's unregulated/illicit fentanyl supply. As a result, people who use fentanyl often need higher doses to feel stable. Because methadone must be started at low doses and increased slowly, it can take weeks before someone reaches an effective dose. This process becomes even longer when doses are missed, since treatment often needs to be restarted at a lower level.
The Methadone Rapid Restart is a newer strategy designed to take ongoing fentanyl use into account. Early clinical experience and modelling suggest that many people who use fentanyl have high opioid tolerance and may be able to return to their previous stable methadone dose even after several missed days, without added safety risk. This approach has shown promise in small clinical settings, but it is not yet known whether it provides better outcomes than the standard methadone titration used today. This study will be testing whether this protocol to help rapidly restart people on Methadone is acceptable for patients and use the learning to guide a subsequent larger clinical trial.
Read the detailed description
Canada continues to see the ongoing effects of the illicit drug overdose in the last decade. Fentanyl and fentanyl analogues account for the majority illicit drug overdose deaths with the highest rate of opioid-related deaths in Canada occurring in British Columbia (BC). Despite this rapid rise in unregulated fentanyl use, treatment strategies for people who use unregulated fentanyl still rely on the opioid use disorder (OUD) treatment guidelines developed from research conducted in people using heroin, a relatively less potent opioid. Currently, methadone and buprenorphine are the recommended medications for opiate use disorder (MOUD).
Methadone at higher doses (at least 60-120mg/day) has shown to have greater effectiveness and treatment retention as compared to lower dosages, based on studies with patient populations using heroin (Bromley et al. 2021). It therefore stands to reason that in the age of unregulated fentanyl, even higher doses of methadone are likely necessary to achieve optimal efficacy and retention rates. Despite this, the highest recommended starting dose of methadone is currently 40mg with a maximum of 15 mg increase every 3 days, for those with a known very high tolerance. As a result, it takes several weeks for people using unregulated fentanyl to reach an effective dose, which is further compounded by missed doses. It is also recommended that if 4 doses of methadone are missed, patients restart at at 50% of their previous dose or at 30-40mg, whichever is higher; and if 5 or more consecutive doses are missed, patients receive a full re-titration, starting from 30-40mg. However, emerging clinical and pharmacokinetic data suggest that, as long as opioid tolerance remains unchanged, methadone can be safely restarted at the same stable dose after missing 4-8 subsequent doses.
The proposed study aims to determine the safety and efficacy of continuing maintenance dose methadone after 4-8 missed doses in people continuing to use unregulated fentanyl to meet their opioid needs.
- Conditions
- Opioid Use Disorder
- Being tested
- Methadone
- Keywords
- Opioid Use Disorder, Opiate Agonist Therapy, Methadone, Medications for Opiate Use Disorder
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethadoneDrug
Also called Metadol-D, Methadose
Participants who meet study inclusion criteria and have no exclusion criteria, who have missed 4-8 doses of methadone will, be administered methadone according to the stratification below and will continue the same dose for the 7 day follow up.
- Arm 1: Previous maintenance treatment with methadone for opioid use disorder at a stable dose for at least 5 consecutive days prior to discontinuing, with allowance for a maximum of 1 missed dose within that 5-day period. These participants will be re-initiated on 100% of their most recent methadone dose.
- Arm 2: Participant was being titrated on methadone prior to discontinuation such that they were on their most recent dosage for less than 5 days but received at least 5 consecutive days of methadone between the prior two dosages (with a maximum of 1 missed dose in that period) be. These participants will be restarted on the lower of their two most recent dosages.
| Study group | Role | What they receive |
|---|---|---|
| Methadone rapid restart for participants on methadone maintenance treatment | Experimental | Participants who have missed 4-8 doses of methadone, but were on maintenance treatment with methadone for opioid use disorder at a stable dose for at least 5 consecutive days prior to discontinuing, with allowance for a maximum of 1 missed dose within that 5-day period. These participants will be re-initiated on 100% of their most recent methadone dose. Receives: Drug: Methadone |
| Methadone rapid restart for participants being titrated on methadone | Experimental | Participants who have missed 4-8 doses of methadone, but were being titrated on methadone prior to discontinuation such that they were on their most recent dosage for less than 5 days but received at least 5 consecutive days of methadone between the prior two dosages (with a maximum of 1 missed dose in that period) be. These participants will be restarted on the lower of their two most recent dosages. Receives: Drug: Methadone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Enrollment rate
Number of participants enrolled per month
Measured: Enrollment
Patient Satisfaction
At the end of the follow up period participants will be asked, "Overall, how satisfied were you with the methadone restart protocol?" The response will be recorded on a 7-point scale: 1=extremely dissatisfied; 2= very dissatisfied; 3= somewhat dissatisfied; 4=neither satisfied nor dissatisfied; 5=somewhat satisfied; 6=very satisfied; 7=extremely satisfied.
Measured: Assessed retrospectively at the end of 7 day follow up period.
Secondary outcomes (11)
Recruitment
Number of patients approached, eligible, and enrolled
Measured: Through study completion, anticipated to be 12 months
Level of sedation
Pasero Opioid-Induced Sedation Scale (Score range: 1-4) : Minimal/No sedation (score: 1-2), High sedation (score: 3-4)
Measured: Baseline, Intervention (1, 2, and 3 hour post-dose) and follow up (Day 1, 3 and 7)
Blood Pressure
Systolic and diastolic blood pressure
Measured: Baseline, intervention (1,2, and 3 hour post methadone dose), and follow up (Day 1, 3, and 7)
Oxygen saturation
Oxygen saturation
Measured: Baseline, intervention (1, 2, and, 3 hour post dose) and follow up (Day 1, 3, and 7)
Respiratory rate
Respiration rate
Measured: Baseline, intervention (1, 2 and 3 hour after post methadone dose), and follow up (Day 1, 3, and 7)
Heart rate
Heart rate
Measured: Baseline, intervention (1, 2 and 3 hour after post methadone dose), and follow up (Day 1, 3, and 7)
Change in unregulated substance use patterns
The change in the unregulated substance use patterns assessed at baseline and end of the methadone restart protocol
Measured: Baseline and follow up (Day 1, 3, and 7)
ECG
QTc levels in Electrocardiogram
Measured: Baseline and follow up (Day 3 and 7)
Adverse events
Incidence of adverse events (AEs) possibly/probably/definitely related to the study drug
Measured: During intervention and follow up
OAT retention
Retention of methadone and other opioid agonist therapy
Measured: Follow up
Overdose and hospitalization
Rate of overdose and hospitalization
Measured: Follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2026
- Study startMay 2026 (estimated)
- Primary completionMar 2027 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Opioid Use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pouya Azar
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Pouya Azar, University of British Columbia
- Investigators
- Pouya Azar, Principal investigator, Department of Psychiatry, Faculty of Medicine, University of British Columbia and Vancouver General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07546396
- Sponsor's protocol ID
- H25-03989
- Status last verified
- Apr 2026
- First submitted
- 18 Mar 2026
- Last updated
- 22 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Methadone Rapid Restart Study
- ClinicalTrials.gov ID
- NCT07546396
- Acronym / sponsor ID
- H25-03989
- Conditions
- Opioid Use Disorder
- Keywords
- Opioid Use Disorder, Opiate Agonist Therapy, Methadone, Medications for Opiate Use Disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Pouya AzarUniversity, hospital or other
- Study start
- May 2026 (estimated)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 22 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The usual treatment for opioid use disorder (OUD) is opioid agonist therapy (OAT) with either methadone or buprenorphine. These treatments are well-established, reduce the risk of fatal overdoses, and are considered the standard approach. However, current methadone guidelines were developed when most people were using heroin, which is far less potent than today's unregulated/illicit fentanyl supply. As a result, people who use fentanyl often need higher doses to feel stable. Because methadone must be started at low doses and increased slowly, it can take weeks before someone reaches an effective dose. This process becomes even longer when doses are missed, since treatment often needs to be restarted at a lower level.
The Methadone Rapid Restart is a newer strategy designed to take ongoing fentanyl use into account. Early clinical experience and modelling suggest that many people who use fentanyl have high opioid tolerance and may be able to return to their previous stable methadone dose even after several missed days, without added safety risk. This approach has shown promise in small clinical settings, but it is not yet known whether it provides better outcomes than the standard methadone titration used today. This study will be testing whether this protocol to help rapidly restart people on Methadone is acceptable for patients and use the learning to guide a subsequent larger clinical trial.
Detailed description
Canada continues to see the ongoing effects of the illicit drug overdose in the last decade. Fentanyl and fentanyl analogues account for the majority illicit drug overdose deaths with the highest rate of opioid-related deaths in Canada occurring in British Columbia (BC). Despite this rapid rise in unregulated fentanyl use, treatment strategies for people who use unregulated fentanyl still rely on the opioid use disorder (OUD) treatment guidelines developed from research conducted in people using heroin, a relatively less potent opioid. Currently, methadone and buprenorphine are the recommended medications for opiate use disorder (MOUD).
Methadone at higher doses (at least 60-120mg/day) has shown to have greater effectiveness and treatment retention as compared to lower dosages, based on studies with patient populations using heroin (Bromley et al. 2021). It therefore stands to reason that in the age of unregulated fentanyl, even higher doses of methadone are likely necessary to achieve optimal efficacy and retention rates. Despite this, the highest recommended starting dose of methadone is currently 40mg with a maximum of 15 mg increase every 3 days, for those with a known very high tolerance. As a result, it takes several weeks for people using unregulated fentanyl to reach an effective dose, which is further compounded by missed doses. It is also recommended that if 4 doses of methadone are missed, patients restart at at 50% of their previous dose or at 30-40mg, whichever is higher; and if 5 or more consecutive doses are missed, patients receive a full re-titration, starting from 30-40mg. However, emerging clinical and pharmacokinetic data suggest that, as long as opioid tolerance remains unchanged, methadone can be safely restarted at the same stable dose after missing 4-8 subsequent doses.
The proposed study aims to determine the safety and efficacy of continuing maintenance dose methadone after 4-8 missed doses in people continuing to use unregulated fentanyl to meet their opioid needs.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methadone rapid restart for participants on methadone maintenance treatment | Experimental | Drug: MethadoneParticipants who have missed 4-8 doses of methadone, but were on maintenance treatment with methadone for opioid use disorder at a stable dose for at least 5 consecutive days prior to discontinuing, with allowance for a maximum of 1 missed dose within that 5-day period. These participants will be re-initiated on 100% of their most recent methadone dose. |
| Methadone rapid restart for participants being titrated on methadone | Experimental | Drug: MethadoneParticipants who have missed 4-8 doses of methadone, but were being titrated on methadone prior to discontinuation such that they were on their most recent dosage for less than 5 days but received at least 5 consecutive days of methadone between the prior two dosages (with a maximum of 1 missed dose in that period) be. These participants will be restarted on the lower of their two most recent dosages. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Age 19 years or older
- Opioid use disorder (OUD) of any severity by DSM-5 TR Clinical Diagnostic criteria [American Psychiatric Association, 2022]
- Previously 'stable' on methadone as per the below definitions:
- Missed 4-8 doses of methadone in a row leading up to intake assessment.
- Participant able to provide baseline opiate use history as per opiate use screening questions in Appendix A. This must provide an estimate of opiate use prior to stopping methadone and change in use since stopping.
Key exclusion criteria (7 listed)
- COWS score of 8 or more at the time of clinician assessment
- Self-reported Opioid overdose or naloxone administration since methadone discontinuation or during the 5 days prior to methadone discontinuation
- Self-reported New cardiac disease diagnosis since methadone discontinuation
- Self-reported Intolerable side effects reported when taking methadone
- Individuals who are pregnant (urine pregnancy test) or breast-feeding (self-reported)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethadoneAlso: Metadol-D, MethadoseParticipants who meet study inclusion criteria and have no exclusion criteria, who have missed 4-8 doses of methadone will, be administered methadone according to the stratification below and will continue the same dose for the 7 day follow up. * Arm 1: Previous maintenance treatment with methadone for opioid use disorder at a stable dose for at least 5 consecutive days prior to discontinuing, with allowance for a maximum of 1 missed dose within that 5-day period. These participants will be re-initiated on 100% of their most recent methadone dose. * Arm 2: Participant was being titrated on methadone prior to discontinuation such that they were on their most recent dosage for less than 5 days but received at least 5 consecutive days of methadone between the prior two dosages (with a maximum of 1 missed dose in that period) be. These participants will be restarted on the lower of their two most recent dosages. | Drug | Methadone rapid restart for participants being titrated on methadone, Methadone rapid restart for participants on methadone maintenance treatment |
Primary outcome
Enrollment rate
Time frame: Enrollment
Number of participants enrolled per month
Patient Satisfaction
Time frame: Assessed retrospectively at the end of 7 day follow up period.
At the end of the follow up period participants will be asked, "Overall, how satisfied were you with the methadone restart protocol?" The response will be recorded on a 7-point scale: 1=extremely dissatisfied; 2= very dissatisfied; 3= somewhat dissatisfied; 4=neither satisfied nor dissatisfied; 5=somewhat satisfied; 6=very satisfied; 7=extremely satisfied.
11 secondary outcomes
Recruitment
Time frame: Through study completion, anticipated to be 12 months
Level of sedation
Time frame: Baseline, Intervention (1, 2, and 3 hour post-dose) and follow up (Day 1, 3 and 7)
Blood Pressure
Time frame: Baseline, intervention (1,2, and 3 hour post methadone dose), and follow up (Day 1, 3, and 7)
Oxygen saturation
Time frame: Baseline, intervention (1, 2, and, 3 hour post dose) and follow up (Day 1, 3, and 7)
Respiratory rate
Time frame: Baseline, intervention (1, 2 and 3 hour after post methadone dose), and follow up (Day 1, 3, and 7)
Heart rate
Time frame: Baseline, intervention (1, 2 and 3 hour after post methadone dose), and follow up (Day 1, 3, and 7)
Change in unregulated substance use patterns
Time frame: Baseline and follow up (Day 1, 3, and 7)
ECG
Time frame: Baseline and follow up (Day 3 and 7)
Adverse events
Time frame: During intervention and follow up
OAT retention
Time frame: Follow up
Overdose and hospitalization
Time frame: Follow up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Pouya Azar principal investigator
Department of Psychiatry, Faculty of Medicine, University of British Columbia and Vancouver General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Methadone in people with Opioid Use Disorder, run by Pouya Azar at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 22 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact James Wong ((604) 875-5823, james.wong@vch.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Enrollment rate (time frame: Enrollment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2026.