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Surmounting Withdrawal to Initiate Fast Treatment With Naltrexone (SWIFT)

N

New York State Psychiatric Institute

Status

Completed

Conditions

Opioid-use Disorder

Treatments

Other: Standard Induction Procedure (SP)
Other: Rapid Induction Procedure (RP)

Study type

Interventional

Funder types

Other
Industry
NIH

Identifiers

NCT04762537
CTN-0097
UG1DA013035-19 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

This study compares two methods of initiating treatment with extended-release naltrexone (XR-NTX) when implemented at community-based inpatient or residential programs. The primary goal of this hybrid effectiveness-implementation study is to determine whether the Rapid Method (5-7 day long) is non-inferior to a Standard Method (13-day long) on the primary effectiveness outcome of successful initiation of XR-NTX (receiving the first injection). Secondary objectives include comparing Rapid versus Standard method on: time from admission to first dose of XR-NTX and time to dropout, craving, withdrawal severity, retention, abstinence, and safety measures, as measured during the inpatient induction process and the first two months of post-induction XR-NTX maintenance. Other exploratory outcomes include predictors of initiation success, and economic analyses. The implementation goal is to operationalize an implementation facilitation strategy that will be used to train clinical sites on the XR-NTX initiation method, to capture fidelity to the rapid induction process, and to study barriers and facilitators to implementation and refine the implementation facilitation strategy accordingly.

Full description

The overarching objective of the SWIFT trial (CTN-0097) is to foster widespread adoption of a regimen for rapid initiation of treatment with extended-release injection naltrexone (XR-NTX) at inpatient or residential Community Treatment Programs (CTPs). If widely adopted, such a regimen would have a substantial public health impact by expanding medication treatment options offered to patients with OUD to include XR-NTX.

In multi-site, randomized (subject level) trials, XR-NTX, once initiated, has been found to have similar effectiveness to sublingual buprenorphine on clinical outcomes of retention in treatment and abstinence from opioids. However, initiation of naltrexone often involves a significant (up to 2 weeks) delay, which is a clinical hurdle that impedes the widespread adoption of XR-NTX as a treatment option. Initiation of naltrexone in patients actively using opioids requires that a patient be detoxified first, and the official prescribing information for XR-NTX recommends an additional 7- to 10-day waiting period after last dose of opioid before administering XR-NTX. This standard initiation regimen, involving a brief period of agonist, usually buprenorphine, taper followed by a 7- to 10-day waiting period, takes approximately two weeks. During this time, patients are vulnerable to drop out and relapse; further, this waiting period is problematic in the face of funding restrictions on the duration of inpatient stays. In a single-site randomized trial, a Rapid naltrexone induction method utilizing minimal buprenorphine, non-opioid medications to treat withdrawal symptoms, and upward titration of oral naltrexone starting with small doses, XR-NTX initiation was accomplished in 5 to 7 days and was found superior to the standard 14-day approach on the proportion of patients initiating XR-NTX.

The primary goal of this hybrid effectiveness-implementation study is to determine whether the Rapid method of initiating treatment with XR-NTX is non-inferior to a standard method on the primary effectiveness outcome of successful initiation of XR-NTX (receiving the first injection) when implemented at community-based inpatient or residential programs. Secondary objectives include comparing rapid versus standard method of XR-NTX initiation on: time from admission to first dose of XR-NTX and time to dropout, craving, withdrawal severity, retention, abstinence, and safety measures, as measured during the inpatient initiation process and the first two months post XR-NTX induction. Other exploratory outcomes include predictors of initiation success, and economic analyses. The implementation goal is to operationalize an implementation facilitation strategy that will be used to train clinical sites on the XR-NTX initiation method, to capture fidelity to the rapid induction process, and to study barriers and facilitators to implementation and refine the implementation facilitation strategy accordingly.

Enrollment

415 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  1. 18 years of age or older.
  2. Meets current Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for opioid use disorder.
  3. Seeking treatment for opioid use disorder, willing to accept treatment with XR- NTX and, in the judgment of the treating physician, is a good candidate for naltrexone- based treatment.
  4. Willing and able to provide written informed consent.
  5. Able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study.
  6. If female of childbearing potential, willing to practice an effective method of birth control for the duration of participation in the study.

Exclusion criteria

  1. Serious medical, psychiatric or substance use disorder that, in the opinion of the study physician, would make a detoxification and naltrexone initiation, or maintenance treatment with XR-NTX, hazardous (relative contra-indications) or requires a different level of care. Examples include:

  2. Disabling or terminal medical illness (e.g., uncompensated heart failure, severe acute hepatitis, cirrhosis or end-stage liver disease) as assessed by medical history and/or review of systems.

  3. Severe, untreated or inadequately treated mental disorder (e.g., active psychosis, uncontrolled manic-depressive illness) as assessed by history and/or clinical interview.

  4. Current severe alcohol, benzodiazepine, or other depressant or sedative hypnotic use likely to require a complicated medical detoxification (routine alcohol and sedative detoxifications may be included).

  5. Suicidal or homicidal ideation that requires immediate attention. Known allergy or sensitivity to buprenorphine, naloxone, naltrexone, polylactide-co-glycolide, carboxymethylcellulose, or other components of the Vivitrol® diluent.

    1. Maintenance treatment with methadone. 4. Maintenance treatment with buprenorphine unless the patient is determined to have a poor treatment response (in the form of buprenorphine non-adherence with or without the use of illicit opioids), warranting change to XR-NTX treatment.

    2. Presence of pain of sufficient severity as to require ongoing pain management with opioids.

    3. Circumstances (legal, personal, occupational) that would threaten the feasibility of XR- NTX treatment or make another treatment (e.g. buprenorphine or methadone) a better choice.

    4. Are currently in jail, prison or other overnight facility as required by court of law or have pending legal action that could prevent participation in study activities.

    5. If female, currently pregnant or breastfeeding, or planning on conception. 9. Body habitus that, in the judgment of the study physician, precludes safe intramuscular injection of XR-NTX (e.g., BMI>40, excess fat tissue over the buttocks, emaciation).

    6. Admitted to the inpatient detoxification or residential rehabilitation unit more than 3 days prior to consent.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

None (Open label)

415 participants in 2 patient groups

Standard Induction Method
Active Comparator group
Description:
The Standard Method (13-day long) includes 5-days of buprenorphine taper followed by 7-day washout period
Treatment:
Other: Standard Induction Procedure (SP)
Rapid Induction Method
Experimental group
Description:
The Rapid Method includes one day of buprenorphine followed by a day of washout and 3-4 days of oral naltrexone titration with adjunctive medications
Treatment:
Other: Rapid Induction Procedure (RP)

Trial documents
2

Trial contacts and locations

6

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Data sourced from clinicaltrials.gov

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