Surmounting Withdrawal to Initiate Fast Treatment With Naltrexone

NCT04762537 | Completed Results DMC

• 2 other identifiers: CTN-0097UG1DA013035-19
• Study Type: interventional
• Target: 415
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Opioid-use Disorder

Outcome Measures

Primary Outcomes (1)

• The Percentage of Patients Who Receive the First XR-NTX Injection (Dichotomous: Did or Did Not Receive First Dose of XR-NTX)

  The primary goal of the study is to show RP is non-inferior to SP XR-NTX induction method.

  Induction Phase: 1-30 days

Secondary Outcomes (19)

• Mean for Time From Admission to First XR-NTX Injection by Treatment Group.

  Induction Phase: 1-30 days

• Mean of Individual Participant's Opioid Craving Measured by Visual Analog Scales (VAS) During Induction Phase

  Induction Phase: 1-30 days

• Mean of Individual Participant's Opioid Craving Measured by Visual Analog Scales (VAS) During Post-induction Weeks 1 Through 8

  Post Induction Phase: 1-8 weeks

• Mean of Individual Participant's Opioid Withdrawal Measured by Subjective Opioid Withdrawal Scale (SOWS) During Induction Phase

  Induction Phase: 1-30 days

• Mean of Individual Participant's Opioid Withdrawal Measured by Subjective Opioid Withdrawal Scale (SOWS) During Post-induction Weeks 1 Through 4

  Post Induction Phase: 1 - 4 weeks

Study Arms (2)

Standard Induction Method

ACTIVE COMPARATOR

The Standard Method (13-day long) includes 5-days of buprenorphine taper followed by 7-day washout period

Other: Standard Induction Procedure (SP)

Rapid Induction Method

EXPERIMENTAL

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

Other: Rapid Induction Procedure (RP)

Interventions

Standard Induction Procedure (SP) OTHER

SP includes stabilization on buprenorphine (6-8 mg) on Day 1 followed by a taper over the subsequent 4 days. After the completion of buprenorphine taper, participants will enter a washout period of at least 8 days. On the last day of the washout period, participants will be evaluated for eligibility to receive XR-NTX injection. Once found eligible, an XR-NTX injection will be given.

Standard Induction Method

Rapid Induction Procedure (RP) OTHER

RP includes 1 day of buprenorphine 6-8 mg, followed by a day of washout and 4 days of oral naltrexone titration. If the participant is able to tolerate the last dose of the naltrexone titration, an XR-NTX injection will be given

Rapid Induction Method

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older.
• Meets current Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for opioid use disorder.
• 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.
• Willing and able to provide written informed consent.
• Able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study.
• If female of childbearing potential, willing to practice an effective method of birth control for the duration of participation in the study.

You may not qualify if:

• \. 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:
• 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.
• Severe, untreated or inadequately treated mental disorder (e.g., active psychosis, uncontrolled manic-depressive illness) as assessed by history and/or clinical interview.
• 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).
• 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.
• \. 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.
• \. Presence of pain of sufficient severity as to require ongoing pain management with opioids.
• \. 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.
• \. 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.
• \. 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).
• \. Admitted to the inpatient detoxification or residential rehabilitation unit more than 3 days prior to consent.

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• National Institute on Drug Abuse (NIDA): collaborator
• The Emmes Company, LLC: collaborator

Study Sites (6)

Aspire Health Partners

Orlando, Florida, 32810, United States

Location

Avery Road Treatment Center

Rockville, Maryland, 20853, United States

Location

Gibson Recovery Center, Inc.

Cape Girardeau, Missouri, 63703, United States

Location

Stony Brook Eastern Long Island Hospital

Greenport, New York, 11944, United States

Location

Adapt

Roseburg, Oregon, 97470, United States

Location

Nexus Recovery Center, Inc.

Dallas, Texas, 75228, United States

Location

Related Publications (3)

• Sullivan M, Bisaga A, Pavlicova M, Choi CJ, Mishlen K, Carpenter KM, Levin FR, Dakwar E, Mariani JJ, Nunes EV. Long-Acting Injectable Naltrexone Induction: A Randomized Trial of Outpatient Opioid Detoxification With Naltrexone Versus Buprenorphine. Am J Psychiatry. 2017 May 1;174(5):459-467. doi: 10.1176/appi.ajp.2016.16050548. Epub 2017 Jan 10.

  PMID: 28068780 RESULT

• Shulman M, Greiner MG, Tafessu HM, Opara O, Ohrtman K, Potter K, Hefner K, Jelstrom E, Rosenthal RN, Wenzel K, Fishman M, Rotrosen J, Ghitza UE, Nunes EV, Bisaga A. Rapid Initiation of Injection Naltrexone for Opioid Use Disorder: A Stepped-Wedge Cluster Randomized Clinical Trial. JAMA Netw Open. 2024 May 1;7(5):e249744. doi: 10.1001/jamanetworkopen.2024.9744.

  PMID: 38717773 DERIVED

• Greiner MG, Shulman M, Opara O, Potter K, Voronca DC, Tafessu HM, Hefner K, Hamilton A, Scheele C, Ho R, Dresser L, Jelstrom E, Fishman M, Ghitza UE, Rotrosen J, Nunes EV, Bisaga A. Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone (SWIFT): A stepped wedge hybrid type 1 effectiveness-implementation study. Contemp Clin Trials. 2023 May;128:107148. doi: 10.1016/j.cct.2023.107148. Epub 2023 Mar 15.

  PMID: 36931426 DERIVED

MeSH Terms

Conditions

Opioid-Related Disorders

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Results Point of Contact

• Title: Kenzie Potter
• Organization: New York Psychiatric Institute

kenzie.potter@nyspi.columbia.edu

2535920386

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Model Details: The proposed study is an open-label, multi-center, stepped-wedge cluster randomized trial. As part of the stepped-wedge design proposed for this trial, one site, randomly chosen, will start implementing the Rapid procedure (RP) and will remain in this arm for the rest of the study. The next 4 sites randomly chosen will first implement the Standard procedure (SP), to establish the within-site comparison condition, and then at selected staggered time-points (steps) will switch to implementing only the RP. The 6th site (after 5 sites have been randomized to RP) will remain in the SP procedure arm throughout the whole duration of the study. Implementation of RP at study sites will be staggered by 14 weeks and the order in which sites will cross-over from SP to RP will be randomly chosen.

Study Record Dates

• First Submitted: January 21, 2021
• First Posted: February 21, 2021
• Study Start: March 16, 2021
• Primary Completion: July 19, 2022
• Study Completion: December 21, 2022
• Last Updated: September 18, 2023
• Results First Posted: September 18, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.

Locations

US (6)