Rapid intravenous symptom-inhibiting fentanyl induction (SIFI) to optimize rotation onto oral opioid agonist therapy among individuals who use unregulated fentanyl: protocol for an open-label, single arm clinical trial
Abstract Background Most opioid use disorder (OUD) treatment guidelines target community medical settings, and the subsequent recommendations were established to prioritize safety and reduce diversion prior to the fentanyl era. For people with OUD who use unregulated fentanyl, slow induction onto op...
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BMC
2025-07-01
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| Series: | Addiction Science & Clinical Practice |
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| Online Access: | https://doi.org/10.1186/s13722-025-00586-7 |
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| author | Pouya Azar Martha J. Ignaszewski Marianne Harris Zoran Barazanci Ruth Davison James S. H. Wong Anil Maharaj Nickie Mathew David Hall Silvia A. Guillemi Julie Foreman Rolando Barrios Julio S. G. Montaner |
| author_facet | Pouya Azar Martha J. Ignaszewski Marianne Harris Zoran Barazanci Ruth Davison James S. H. Wong Anil Maharaj Nickie Mathew David Hall Silvia A. Guillemi Julie Foreman Rolando Barrios Julio S. G. Montaner |
| author_sort | Pouya Azar |
| collection | DOAJ |
| description | Abstract Background Most opioid use disorder (OUD) treatment guidelines target community medical settings, and the subsequent recommendations were established to prioritize safety and reduce diversion prior to the fentanyl era. For people with OUD who use unregulated fentanyl, slow induction onto opioid agonist therapy (OAT) with gradual dose titration is often ineffective or insufficient for reducing withdrawal symptoms and cravings, thereby hampering engagement and retention in treatment. Given the severe risks associated with continued use of the increasingly toxic unregulated drug supply, new and innovative approaches to the management of OUD are urgently needed. We have developed an alternative induction protocol, using a rapid intravenous symptom-inhibiting fentanyl induction (SIFI) to optimize rotation onto oral OAT. Methods An open-label, single arm, prospective pilot clinical trial is being conducted in an outpatient setting to assess the safety, feasibility, and efficacy of a rapid symptom-inhibiting intravenous fentanyl induction protocol to establish starting doses of methadone or sustained-release oral morphine (SROM) based on individual opioid requirements, as a treatment strategy for individuals with OUD who use unregulated fentanyl. The primary outcome is safety, as defined by occurrence of study drug-related adverse events (including but not limited to opioid toxicity and QT interval prolongation) that require intervention during induction and the first 7 days on OAT. Secondary objectives are to determine whether the SIFI protocol will result in use of higher-than-standard starting doses of methadone and SROM, and to determine whether implementation of this protocol will be acceptable to participants and will result in reduced withdrawal symptoms, improved retention, and better long-term outcomes on OAT. Discussion This is the first study to rapidly and objectively estimate opioid tolerance and use it to calculate individualized starting doses of oral OAT in an outpatient setting among people who use unregulated fentanyl. We predict that starting methadone or SROM with individually-tailored doses will lead to therapeutic target concentrations being achieved quickly, safely, and with good patient satisfaction. This approach has the potential to more effectively and safely initiate OAT, to minimize opioid withdrawal and cravings, and in turn to decrease unregulated fentanyl use and increase retention on life-saving OAT. Trial registration ClinicalTrials.gov, NCT05905367; date of registration: June 15, 2023; latest update posted July 18, 2024. https://clinicaltrials.gov/study/NCT05905367 Protocol version: 4.0, April 22, 2024. |
| format | Article |
| id | doaj-art-589d81d4b91b45e49bdae7e465ea0028 |
| institution | DOAJ |
| issn | 1940-0640 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | Addiction Science & Clinical Practice |
| spelling | doaj-art-589d81d4b91b45e49bdae7e465ea00282025-08-20T03:05:13ZengBMCAddiction Science & Clinical Practice1940-06402025-07-0120111310.1186/s13722-025-00586-7Rapid intravenous symptom-inhibiting fentanyl induction (SIFI) to optimize rotation onto oral opioid agonist therapy among individuals who use unregulated fentanyl: protocol for an open-label, single arm clinical trialPouya Azar0Martha J. Ignaszewski1Marianne Harris2Zoran Barazanci3Ruth Davison4James S. H. Wong5Anil Maharaj6Nickie Mathew7David Hall8Silvia A. Guillemi9Julie Foreman10Rolando Barrios11Julio S. G. Montaner12Complex Pain and Addiction Services, Vancouver General HospitalComplex Pain and Addiction Services, Vancouver General HospitalBritish Columbia Centre for Excellence in HIV/AIDSBritish Columbia Centre for Excellence in HIV/AIDSBritish Columbia Centre for Excellence in HIV/AIDSComplex Pain and Addiction Services, Vancouver General HospitalPharmacokinetics Modeling and Simulation Laboratory, Faculty of Pharmaceutical Sciences, University of British ColumbiaDepartment of Psychiatry, University of British ColumbiaBritish Columbia Centre for Excellence in HIV/AIDSBritish Columbia Centre for Excellence in HIV/AIDSBritish Columbia Centre for Excellence in HIV/AIDSBritish Columbia Centre for Excellence in HIV/AIDSBritish Columbia Centre for Excellence in HIV/AIDSAbstract Background Most opioid use disorder (OUD) treatment guidelines target community medical settings, and the subsequent recommendations were established to prioritize safety and reduce diversion prior to the fentanyl era. For people with OUD who use unregulated fentanyl, slow induction onto opioid agonist therapy (OAT) with gradual dose titration is often ineffective or insufficient for reducing withdrawal symptoms and cravings, thereby hampering engagement and retention in treatment. Given the severe risks associated with continued use of the increasingly toxic unregulated drug supply, new and innovative approaches to the management of OUD are urgently needed. We have developed an alternative induction protocol, using a rapid intravenous symptom-inhibiting fentanyl induction (SIFI) to optimize rotation onto oral OAT. Methods An open-label, single arm, prospective pilot clinical trial is being conducted in an outpatient setting to assess the safety, feasibility, and efficacy of a rapid symptom-inhibiting intravenous fentanyl induction protocol to establish starting doses of methadone or sustained-release oral morphine (SROM) based on individual opioid requirements, as a treatment strategy for individuals with OUD who use unregulated fentanyl. The primary outcome is safety, as defined by occurrence of study drug-related adverse events (including but not limited to opioid toxicity and QT interval prolongation) that require intervention during induction and the first 7 days on OAT. Secondary objectives are to determine whether the SIFI protocol will result in use of higher-than-standard starting doses of methadone and SROM, and to determine whether implementation of this protocol will be acceptable to participants and will result in reduced withdrawal symptoms, improved retention, and better long-term outcomes on OAT. Discussion This is the first study to rapidly and objectively estimate opioid tolerance and use it to calculate individualized starting doses of oral OAT in an outpatient setting among people who use unregulated fentanyl. We predict that starting methadone or SROM with individually-tailored doses will lead to therapeutic target concentrations being achieved quickly, safely, and with good patient satisfaction. This approach has the potential to more effectively and safely initiate OAT, to minimize opioid withdrawal and cravings, and in turn to decrease unregulated fentanyl use and increase retention on life-saving OAT. Trial registration ClinicalTrials.gov, NCT05905367; date of registration: June 15, 2023; latest update posted July 18, 2024. https://clinicaltrials.gov/study/NCT05905367 Protocol version: 4.0, April 22, 2024.https://doi.org/10.1186/s13722-025-00586-7FentanylMethadoneOpioid use disorderOpioid substitution treatment |
| spellingShingle | Pouya Azar Martha J. Ignaszewski Marianne Harris Zoran Barazanci Ruth Davison James S. H. Wong Anil Maharaj Nickie Mathew David Hall Silvia A. Guillemi Julie Foreman Rolando Barrios Julio S. G. Montaner Rapid intravenous symptom-inhibiting fentanyl induction (SIFI) to optimize rotation onto oral opioid agonist therapy among individuals who use unregulated fentanyl: protocol for an open-label, single arm clinical trial Addiction Science & Clinical Practice Fentanyl Methadone Opioid use disorder Opioid substitution treatment |
| title | Rapid intravenous symptom-inhibiting fentanyl induction (SIFI) to optimize rotation onto oral opioid agonist therapy among individuals who use unregulated fentanyl: protocol for an open-label, single arm clinical trial |
| title_full | Rapid intravenous symptom-inhibiting fentanyl induction (SIFI) to optimize rotation onto oral opioid agonist therapy among individuals who use unregulated fentanyl: protocol for an open-label, single arm clinical trial |
| title_fullStr | Rapid intravenous symptom-inhibiting fentanyl induction (SIFI) to optimize rotation onto oral opioid agonist therapy among individuals who use unregulated fentanyl: protocol for an open-label, single arm clinical trial |
| title_full_unstemmed | Rapid intravenous symptom-inhibiting fentanyl induction (SIFI) to optimize rotation onto oral opioid agonist therapy among individuals who use unregulated fentanyl: protocol for an open-label, single arm clinical trial |
| title_short | Rapid intravenous symptom-inhibiting fentanyl induction (SIFI) to optimize rotation onto oral opioid agonist therapy among individuals who use unregulated fentanyl: protocol for an open-label, single arm clinical trial |
| title_sort | rapid intravenous symptom inhibiting fentanyl induction sifi to optimize rotation onto oral opioid agonist therapy among individuals who use unregulated fentanyl protocol for an open label single arm clinical trial |
| topic | Fentanyl Methadone Opioid use disorder Opioid substitution treatment |
| url | https://doi.org/10.1186/s13722-025-00586-7 |
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