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
Bibliographic record
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.024 | 0.023 |
| Meta-epidemiology (narrow) | 0.005 | 0.002 |
| Meta-epidemiology (broad) | 0.007 | 0.003 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.002 | 0.004 |
| Scholarly communication | 0.003 | 0.003 |
| Open science | 0.004 | 0.002 |
| Research integrity | 0.005 | 0.008 |
| Insufficient payload (model declined to judge) | 0.031 | 0.008 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".