Opioid-use Disorder
Conditions
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.
Detailed 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.
Interventions
OTHERStandard Induction Procedure (SP)
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.
OTHERRapid Induction Procedure (RP)
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
Sponsors
National Institute on Drug Abuse (NIDA)
The Emmes Company, LLC
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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: 1. 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. 2. Severe, untreated or inadequately treated mental disorder (e.g., active psychosis, uncontrolled manic-depressive illness) as assessed by history and/or clinical interview. 3. 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). 4. 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. 3\. 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. 5\. Presence of pain of sufficient severity as to require ongoing pain management with opioids. 6\. 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. 7\. 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. 8\. 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). 10\. Admitted to the inpatient detoxification or residential rehabilitation unit more than 3 days prior to consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Patients Who Receive the First XR-NTX Injection (Dichotomous: Did or Did Not Receive First Dose of XR-NTX) | Induction Phase: 1-30 days | The primary goal of the study is to show RP is non-inferior to SP XR-NTX induction method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean of Individual Participant's Opioid Craving Measured by Visual Analog Scales (VAS) During Induction Phase | Induction Phase: 1-30 days | Craving for opioids measured by Visual Analog Scales (VAS). Scale 0-100, 0 no craving and 100 Most intense craving possible |
| 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 | Craving for opioids measured by Visual Analog Scales (VAS). Scale 0-100, 0 no craving and 100 Most intense craving possible |
| Mean of Individual Participant's Opioid Withdrawal Measured by Subjective Opioid Withdrawal Scale (SOWS) During Induction Phase | Induction Phase: 1-30 days | Opioid withdrawal symptoms as measured by the Subjective Opioid Withdrawal Scale (SOWS). Scale 0-64, with the higher score representing greater withdrawal severity. |
| 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 | Opioid withdrawal symptoms as measured by the Subjective Opioid Withdrawal Scale (SOWS). Scale 0-64, with the higher score representing greater withdrawal severity. |
| Mean of Individual Participant's Opioid Withdrawal Measured by Clinical Opioid Withdrawal Scale (COWS) During Induction Phase | Induction Phase: 1-30 days | Opioid withdrawal symptoms as measured by the Clinical Opiate Withdrawal Scale (COWS). Scale 0-59, with the higher score representing greater withdrawal severity. |
| Mean of Individual Participant's Opioid Craving Measured by Clinical Opioid Withdrawal Scale (COWS) During Post-induction Weeks 1 Through 4 | Post Induction Phase: 1 - 4 weeks | Opioid withdrawal symptoms as measured by the Clinical Opiate Withdrawal Scale (COWS). Scale 0-59, with the higher score representing greater withdrawal severity. |
| Mean for Individual Participant's Patient Health Questionnaire (PHQ-9) Score During Induction Phase | Induction Phase: 1-30 days | Other depressive, anxiety, and subacute withdrawal symptoms as measured by the Patient Health Questionnaire-9 (PHQ-9). Scale 0-27, with the higher score representing greater severity. |
| Mean for Individual Participant's Patient Health Questionnaire (PHQ-9) Score During Post-induction Weeks 1 Through 8 | Post Induction Phase: 1 - 8 weeks | Other depressive, anxiety, and subacute withdrawal symptoms as measured by the Patient Health Questionnaire-9 (PHQ-9). Scale 0-27, with the higher score representing greater severity. |
| Mean for Individual Participant's General Anxiety Disorder (GAD-7) Score During Induction Phase | Induction Phase: 1-30 days | Other depressive, anxiety, and subacute withdrawal symptoms as measured by the General Anxiety Disorder-7 (GAD-7). Scale 0-21, with the higher score representing greater severity. |
| Mean for Time From Admission to First XR-NTX Injection by Treatment Group. | Induction Phase: 1-30 days | Time to receipt of first injection of XR-NTX from day of admission for participants that receive first injection of XR-NTX. |
| Frequency of Targeted Safety Events Related to Study Medication and Any Serious Adverse Events During Induction Period and During Eight Weeks of Post-induction Treatment | Induction Phase- 1 - 30 days, Post Induction Phase- 1-8 weeks | Safety, as measured by targeted safety events and serious adverse events. |
| Number of Medical Visits and Therapy Completed During Follow up Treatment. | Post Induction Phase: 1 - 8 weeks | Engagement with medical visits and therapy (based on medical management log, XR- NTX dose log, Psychosocial log). |
| Percent of Patients Reporting Continued Treatment With Medication for Opioid Use Disorder (MOUD) at Week 8 | Post Induction Phase: Week 8 | Use of medication for opioid use disorder (MOUD) as measured by patient self-report on Timeline Followback (TLFB). |
| Percent of Participants Positive for Opioids Using Weekly TLFB During Eight Weeks of Post-induction | Post Induction Phase: 1 - 8 weeks | Opioid abstinence, as measured by the Timeline Followback (TLFB) (self-report days using opioids) |
| Percent of Participants Positive for Opioids Using Urine Drug Screens at Week 4 and 8 | Post Induction Phase: Week 4 and Week 8 | Opioid abstinence, as measured by the proportion of opioid-positive urine tests. |
| Percent of Participants Positive for Cocaine, Sedatives, Alcohol, Cannabis, and Tobacco Using Weekly TLFB During Eight Weeks of Post- Induction | Post Induction Phase: 1 - 8 weeks | Use of alcohol and other drugs of abuse (e.g., cocaine, other stimulants, cannabis, benzodiazepines), by self-report |
| Percent of Participants Positive for Cocaine, Sedatives, Alcohol, Cannabis, and Tobacco Using Urine Drug Screens at Week 4 and 8 | Post Induction Phase: Week 4 and Week 8 | Use of alcohol and other drugs of abuse (e.g., cocaine, other stimulants, cannabis, benzodiazepines), by urine drug screens. |
| Proportion of Participants That Receive Second and Third Injection of XR-NTX (at 1 Month and 2 Months, From First Injection) | Post Induction Phase: Week 4 and Week 8 | Retention in the trial to receive the second and the third XR-NTX injections. |
| Mean for Individual Participant's General Anxiety Disorder (GAD-7) Score During Post-induction Weeks 1 Through 8 | Post Induction Phase: 1 - 8 weeks | Other depressive, anxiety, and subacute withdrawal symptoms as measured by the General Anxiety Disorder-7 (GAD-7). Scale 0-21, with the higher score representing greater severity. |
Countries
United States
Participant flow
Pre-assignment details
451 participants were found eligible at pre-screening, 32 of which did not meet eligibility criteria at screening. Of the 419 participants determined eligible at screening, 4 withdrew interest in participation or left prior to completion of screening and initiation of enrollment. The total remaining 415 were enrolled in one of the study treatment arms.
Participants by arm
| Arm | Count |
|---|---|
| Standard Induction Method The Standard Method (13-day long) includes 5-days of buprenorphine taper followed by 7-day washout period
Standard Induction Procedure (SP): 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. | 190 |
| Rapid Induction Method 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
Rapid Induction Procedure (RP): 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 | 225 |
| Total | 415 |
Baseline characteristics
| Characteristic | Rapid Induction Method | Standard Induction Method | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Categorical >=65 years | 199 Participants | 168 Participants | 367 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 22 Participants | 46 Participants |
| Baseline substance use (Urine Drug Screen) Amphetamine | 67 Number of positive test results | 36 Number of positive test results | 103 Number of positive test results |
| Baseline substance use (Urine Drug Screen) Barbiturate | 1 Number of positive test results | 1 Number of positive test results | 2 Number of positive test results |
| Baseline substance use (Urine Drug Screen) Benzodiazepines | 116 Number of positive test results | 63 Number of positive test results | 179 Number of positive test results |
| Baseline substance use (Urine Drug Screen) Buprenorphine | 129 Number of positive test results | 127 Number of positive test results | 256 Number of positive test results |
| Baseline substance use (Urine Drug Screen) Cocaine | 49 Number of positive test results | 55 Number of positive test results | 104 Number of positive test results |
| Baseline substance use (Urine Drug Screen) Ecstasy (MDMA) | 7 Number of positive test results | 8 Number of positive test results | 15 Number of positive test results |
| Baseline substance use (Urine Drug Screen) Fentanyl | 140 Number of positive test results | 123 Number of positive test results | 263 Number of positive test results |
| Baseline substance use (Urine Drug Screen) Marijuana | 78 Number of positive test results | 83 Number of positive test results | 161 Number of positive test results |
| Baseline substance use (Urine Drug Screen) Methadone | 4 Number of positive test results | 7 Number of positive test results | 11 Number of positive test results |
| Baseline substance use (Urine Drug Screen) Methamphetamine | 61 Number of positive test results | 38 Number of positive test results | 99 Number of positive test results |
| Baseline substance use (Urine Drug Screen) Opiates | 64 Number of positive test results | 38 Number of positive test results | 102 Number of positive test results |
| Baseline substance use (Urine Drug Screen) Oxycodone | 7 Number of positive test results | 11 Number of positive test results | 18 Number of positive test results |
| Baseline substance use (Urine Drug Screen) Phencyclidine | 0 Number of positive test results | 3 Number of positive test results | 3 Number of positive test results |
| Education Completed Associate's degree: academic program | 8 Participants | 11 Participants | 19 Participants |
| Education Completed Associate's degree: occupational, technical, or vocational program | 9 Participants | 11 Participants | 20 Participants |
| Education Completed Bachelor's degree | 7 Participants | 4 Participants | 11 Participants |
| Education Completed Doctoral degree | 0 Participants | 0 Participants | 0 Participants |
| Education Completed Don't know | 6 Participants | 2 Participants | 8 Participants |
| Education Completed GED or equivalent | 34 Participants | 24 Participants | 58 Participants |
| Education Completed High school graduate | 69 Participants | 58 Participants | 127 Participants |
| Education Completed Less than high school diploma | 49 Participants | 39 Participants | 88 Participants |
| Education Completed Master's degree | 3 Participants | 3 Participants | 6 Participants |
| Education Completed Professional school degree | 0 Participants | 0 Participants | 0 Participants |
| Education Completed Some college, no degree | 40 Participants | 38 Participants | 78 Participants |
| Employment Disabled permanently or temporarily | 4 Participants | 6 Participants | 10 Participants |
| Employment Keeping house | 12 Participants | 3 Participants | 15 Participants |
| Employment Looking for work, unemployed | 140 Participants | 121 Participants | 261 Participants |
| Employment Only temporarily laid off, sick leave, or maternity leave | 15 Participants | 5 Participants | 20 Participants |
| Employment Other | 1 Participants | 3 Participants | 4 Participants |
| Employment Retired | 0 Participants | 1 Participants | 1 Participants |
| Employment Student | 1 Participants | 1 Participants | 2 Participants |
| Employment Working now | 52 Participants | 50 Participants | 102 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 53 Participants | 38 Participants | 91 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 172 Participants | 147 Participants | 319 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 5 Participants | 5 Participants |
| First COWS Score on Day 1 of admission | 4.8 units on a scale STANDARD_DEVIATION 3.53 | 5.7 units on a scale STANDARD_DEVIATION 4.5 | 5.2 units on a scale STANDARD_DEVIATION 3.99 |
| History of lifetime opioid overdose | 111 Participants | 89 Participants | 200 Participants |
| Location participant spent the night before coming to the unit Detox | 1 Participants | 1 Participants | 2 Participants |
| Location participant spent the night before coming to the unit Halfway house, residential treatment program (focus: establishing sobriety) | 3 Participants | 1 Participants | 4 Participants |
| Location participant spent the night before coming to the unit Homeless shelter | 1 Participants | 4 Participants | 5 Participants |
| Location participant spent the night before coming to the unit Hotel, SRO, or boarding home | 8 Participants | 17 Participants | 25 Participants |
| Location participant spent the night before coming to the unit Institution (hospital, nursing home, etc.) | 3 Participants | 4 Participants | 7 Participants |
| Location participant spent the night before coming to the unit Missing | 32 Participants | 22 Participants | 54 Participants |
| Location participant spent the night before coming to the unit Other | 5 Participants | 3 Participants | 8 Participants |
| Location participant spent the night before coming to the unit Other - homeless | 3 Participants | 3 Participants | 6 Participants |
| Location participant spent the night before coming to the unit Other - stable housing | 4 Participants | 1 Participants | 5 Participants |
| Location participant spent the night before coming to the unit Outdoors/street, abandoned/public building, vehicle, or other place not meant for human habitation | 11 Participants | 11 Participants | 22 Participants |
| Location participant spent the night before coming to the unit Own apartment, room or house - not subsidized | 84 Participants | 47 Participants | 131 Participants |
| Location participant spent the night before coming to the unit Own apartment, room or house - subsidized, for example Section 8 or living in public housing | 3 Participants | 9 Participants | 12 Participants |
| Location participant spent the night before coming to the unit Someone else's apartment, room or house | 65 Participants | 66 Participants | 131 Participants |
| Location participant spent the night before coming to the unit Transitional housing (focus: movement into permanent housing) | 2 Participants | 1 Participants | 3 Participants |
| Marital Status Divorced | 28 Participants | 23 Participants | 51 Participants |
| Marital Status Don't know | 10 Participants | 4 Participants | 14 Participants |
| Marital Status Living with partner | 28 Participants | 16 Participants | 44 Participants |
| Marital Status Married | 16 Participants | 15 Participants | 31 Participants |
| Marital Status Never married | 121 Participants | 112 Participants | 233 Participants |
| Marital Status Refused | 0 Participants | 1 Participants | 1 Participants |
| Marital Status Separated | 15 Participants | 15 Participants | 30 Participants |
| Marital Status Widowed | 7 Participants | 4 Participants | 11 Participants |
| Number of lifetime overdoses | 4.1 overdoses STANDARD_DEVIATION 4.59 | 4.5 overdoses STANDARD_DEVIATION 6.92 | 4.3 overdoses STANDARD_DEVIATION 5.73 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 4 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 26 Participants | 28 Participants | 54 Participants |
| Race/Ethnicity, Customized Don't Know | 2 Participants | 10 Participants | 12 Participants |
| Race/Ethnicity, Customized Multiracial | 6 Participants | 16 Participants | 22 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 11 Participants | 12 Participants | 23 Participants |
| Race/Ethnicity, Customized Refused to Answer | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 175 Participants | 115 Participants | 290 Participants |
| Region of Enrollment United States | 225 Participants | 190 Participants | 415 Participants |
| Sex: Female, Male Female | 133 Participants | 77 Participants | 210 Participants |
| Sex: Female, Male Male | 92 Participants | 113 Participants | 205 Participants |
| Sexual-Orientation Bisexual | 24 Participants | 15 Participants | 39 Participants |
| Sexual-Orientation Gay or lesbian | 4 Participants | 2 Participants | 6 Participants |
| Sexual-Orientation Heterosexual or straight | 173 Participants | 146 Participants | 319 Participants |
| Sexual-Orientation Missing | 21 Participants | 23 Participants | 44 Participants |
| Sexual-Orientation Not sure | 2 Participants | 1 Participants | 3 Participants |
| Sexual-Orientation Queer | 0 Participants | 2 Participants | 2 Participants |
| Sexual-Orientation Something else | 1 Participants | 1 Participants | 2 Participants |
| Substance use disorder Alcohol use disorder | 111 participants | 105 participants | 216 participants |
| Substance use disorder Amphetamine use disorder | 119 participants | 85 participants | 204 participants |
| Substance use disorder Cannabis use disorder | 159 participants | 129 participants | 288 participants |
| Substance use disorder Cocaine use disorder | 104 participants | 109 participants | 213 participants |
| Substance use disorder Opioid use disorder | 224 participants | 189 participants | 413 participants |
| Substance use disorder Sedative use disorder | 95 participants | 68 participants | 163 participants |
| TLFB substance use (at least once in the past 30 days) Benzodiazepines | 64 # participants with reported use | 28 # participants with reported use | 92 # participants with reported use |
| TLFB substance use (at least once in the past 30 days) Buprenorphine | 16 # participants with reported use | 25 # participants with reported use | 41 # participants with reported use |
| TLFB substance use (at least once in the past 30 days) Cannabis | 114 # participants with reported use | 95 # participants with reported use | 209 # participants with reported use |
| TLFB substance use (at least once in the past 30 days) Cocaine | 61 # participants with reported use | 70 # participants with reported use | 131 # participants with reported use |
| TLFB substance use (at least once in the past 30 days) Ecstasy (MDMA) | 6 # participants with reported use | 18 # participants with reported use | 24 # participants with reported use |
| TLFB substance use (at least once in the past 30 days) Heavy alcohol use (Females: 3 or more; Males: 4 or more (drinks per day)) | 39 # participants with reported use | 36 # participants with reported use | 75 # participants with reported use |
| TLFB substance use (at least once in the past 30 days) Heroin/Fentanyl | 155 # participants with reported use | 141 # participants with reported use | 296 # participants with reported use |
| TLFB substance use (at least once in the past 30 days) Inhalants | 2 # participants with reported use | 1 # participants with reported use | 3 # participants with reported use |
| TLFB substance use (at least once in the past 30 days) Methadone | 3 # participants with reported use | 11 # participants with reported use | 14 # participants with reported use |
| TLFB substance use (at least once in the past 30 days) Methamphetamine | 73 # participants with reported use | 60 # participants with reported use | 133 # participants with reported use |
| TLFB substance use (at least once in the past 30 days) Missing | 29 # participants with reported use | 21 # participants with reported use | 50 # participants with reported use |
| TLFB substance use (at least once in the past 30 days) No opioids (heroine/fentanyl, opioid analgesics, buprenorphine, methadone) | 8 # participants with reported use | 2 # participants with reported use | 10 # participants with reported use |
| TLFB substance use (at least once in the past 30 days) Opioid analgesics | 47 # participants with reported use | 45 # participants with reported use | 92 # participants with reported use |
| TLFB substance use (at least once in the past 30 days) Other amphetamine | 10 # participants with reported use | 9 # participants with reported use | 19 # participants with reported use |
| TLFB substance use (at least once in the past 30 days) Other drugs | 6 # participants with reported use | 1 # participants with reported use | 7 # participants with reported use |
| TLFB substance use (at least once in the past 7 days) Benzodiazepines | 43 # participants with reported use | 18 # participants with reported use | 61 # participants with reported use |
| TLFB substance use (at least once in the past 7 days) Buprenorphine | 11 # participants with reported use | 17 # participants with reported use | 28 # participants with reported use |
| TLFB substance use (at least once in the past 7 days) Cannabis | 87 # participants with reported use | 80 # participants with reported use | 167 # participants with reported use |
| TLFB substance use (at least once in the past 7 days) Cocaine | 42 # participants with reported use | 51 # participants with reported use | 93 # participants with reported use |
| TLFB substance use (at least once in the past 7 days) Ecstasy (MDMA) | 4 # participants with reported use | 10 # participants with reported use | 14 # participants with reported use |
| TLFB substance use (at least once in the past 7 days) Heavy alcohol use (Females: 3 or more; Males: 4 or more (drinks per day)) | 28 # participants with reported use | 27 # participants with reported use | 55 # participants with reported use |
| TLFB substance use (at least once in the past 7 days) Heroin/Fentanyl | 151 # participants with reported use | 132 # participants with reported use | 283 # participants with reported use |
| TLFB substance use (at least once in the past 7 days) Inhalants | 2 # participants with reported use | 1 # participants with reported use | 3 # participants with reported use |
| TLFB substance use (at least once in the past 7 days) Methadone | 1 # participants with reported use | 6 # participants with reported use | 7 # participants with reported use |
| TLFB substance use (at least once in the past 7 days) Methamphetamine | 56 # participants with reported use | 50 # participants with reported use | 106 # participants with reported use |
| TLFB substance use (at least once in the past 7 days) Missing | 29 # participants with reported use | 21 # participants with reported use | 50 # participants with reported use |
| TLFB substance use (at least once in the past 7 days) No opioids (heroin/fentanyl, opioid analgesics, buprenorphine, methadone) | 12 # participants with reported use | 7 # participants with reported use | 19 # participants with reported use |
| TLFB substance use (at least once in the past 7 days) Opioid analgesics | 37 # participants with reported use | 35 # participants with reported use | 72 # participants with reported use |
| TLFB substance use (at least once in the past 7 days) Other amphetamine | 6 # participants with reported use | 5 # participants with reported use | 11 # participants with reported use |
| TLFB substance use (at least once in the past 7 days) Other drugs | 5 # participants with reported use | 1 # participants with reported use | 6 # participants with reported use |
| Type of baseline buprenorphine last use Injection | 0 # participants with reported use | 0 # participants with reported use | 0 # participants with reported use |
| Type of baseline buprenorphine last use Nasal | 0 # participants with reported use | 0 # participants with reported use | 0 # participants with reported use |
| Type of baseline heroin/fentanyl last use from TLFB Injection | 73 # participants with reported use | 56 # participants with reported use | 129 # participants with reported use |
| Type of baseline heroin/fentanyl last use from TLFB Missing | 29 # participants with reported use | 21 # participants with reported use | 50 # participants with reported use |
| Type of baseline heroin/fentanyl last use from TLFB Nasal | 66 # participants with reported use | 54 # participants with reported use | 120 # participants with reported use |
| Type of baseline heroin/fentanyl last use from TLFB No use | 35 # participants with reported use | 28 # participants with reported use | 63 # participants with reported use |
| Type of baseline heroin/fentanyl last use from TLFB Oral | 1 # participants with reported use | 3 # participants with reported use | 4 # participants with reported use |
| Type of baseline heroin/fentanyl last use from TLFB Smoking | 12 # participants with reported use | 25 # participants with reported use | 37 # participants with reported use |
| Type of baseline methadone last use Injection | 0 # participants with reported use | 1 # participants with reported use | 1 # participants with reported use |
| Type of baseline methadone last use Nasal | 0 # participants with reported use | 1 # participants with reported use | 1 # participants with reported use |
| Type of baseline prescription opioid last use Injection | 1 # participants with reported use | 5 # participants with reported use | 6 # participants with reported use |
| Type of baseline prescription opioid last use Nasal | 11 # participants with reported use | 18 # participants with reported use | 29 # participants with reported use |
| Type of baseline prescription opioid last use Smoking | 1 # participants with reported use | 1 # participants with reported use | 2 # participants with reported use |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 190 | 0 / 225 |
| other Total, other adverse events | 7 / 190 | 27 / 225 |
| serious Total, serious adverse events | 7 / 190 | 12 / 225 |
Outcome results
Primary
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.
Time frame: Induction Phase: 1-30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Induction Method | The Percentage of Patients Who Receive the First XR-NTX Injection (Dichotomous: Did or Did Not Receive First Dose of XR-NTX) | 68 Participants |
| Rapid Induction Method | The Percentage of Patients Who Receive the First XR-NTX Injection (Dichotomous: Did or Did Not Receive First Dose of XR-NTX) | 141 Participants |
Secondary
Frequency of Targeted Safety Events Related to Study Medication and Any Serious Adverse Events During Induction Period and During Eight Weeks of Post-induction Treatment
Safety, as measured by targeted safety events and serious adverse events.
Time frame: Induction Phase- 1 - 30 days, Post Induction Phase- 1-8 weeks
Secondary
Mean for Individual Participant's General Anxiety Disorder (GAD-7) Score During Induction Phase
Other depressive, anxiety, and subacute withdrawal symptoms as measured by the General Anxiety Disorder-7 (GAD-7). Scale 0-21, with the higher score representing greater severity.
Time frame: Induction Phase: 1-30 days
Secondary
Mean for Individual Participant's General Anxiety Disorder (GAD-7) Score During Post-induction Weeks 1 Through 8
Other depressive, anxiety, and subacute withdrawal symptoms as measured by the General Anxiety Disorder-7 (GAD-7). Scale 0-21, with the higher score representing greater severity.
Time frame: Post Induction Phase: 1 - 8 weeks
Secondary
Mean for Individual Participant's Patient Health Questionnaire (PHQ-9) Score During Induction Phase
Other depressive, anxiety, and subacute withdrawal symptoms as measured by the Patient Health Questionnaire-9 (PHQ-9). Scale 0-27, with the higher score representing greater severity.
Time frame: Induction Phase: 1-30 days
Secondary
Mean for Individual Participant's Patient Health Questionnaire (PHQ-9) Score During Post-induction Weeks 1 Through 8
Other depressive, anxiety, and subacute withdrawal symptoms as measured by the Patient Health Questionnaire-9 (PHQ-9). Scale 0-27, with the higher score representing greater severity.
Time frame: Post Induction Phase: 1 - 8 weeks
Secondary
Mean for Time From Admission to First XR-NTX Injection by Treatment Group.
Time to receipt of first injection of XR-NTX from day of admission for participants that receive first injection of XR-NTX.
Time frame: Induction Phase: 1-30 days
Population: Only participants who received first injection of XR-NTX were analyzed for days to first injection.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Induction Method | Mean for Time From Admission to First XR-NTX Injection by Treatment Group. | 14.5 Days | Standard Deviation 3.57 |
| Rapid Induction Method | Mean for Time From Admission to First XR-NTX Injection by Treatment Group. | 7.0 Days | Standard Deviation 1.42 |
Secondary
Mean of Individual Participant's Opioid Craving Measured by Clinical Opioid Withdrawal Scale (COWS) During Post-induction Weeks 1 Through 4
Opioid withdrawal symptoms as measured by the Clinical Opiate Withdrawal Scale (COWS). Scale 0-59, with the higher score representing greater withdrawal severity.
Time frame: Post Induction Phase: 1 - 4 weeks
Secondary
Mean of Individual Participant's Opioid Craving Measured by Visual Analog Scales (VAS) During Induction Phase
Craving for opioids measured by Visual Analog Scales (VAS). Scale 0-100, 0 no craving and 100 Most intense craving possible
Time frame: Induction Phase: 1-30 days
Secondary
Mean of Individual Participant's Opioid Craving Measured by Visual Analog Scales (VAS) During Post-induction Weeks 1 Through 8
Craving for opioids measured by Visual Analog Scales (VAS). Scale 0-100, 0 no craving and 100 Most intense craving possible
Time frame: Post Induction Phase: 1-8 weeks
Secondary
Mean of Individual Participant's Opioid Withdrawal Measured by Clinical Opioid Withdrawal Scale (COWS) During Induction Phase
Opioid withdrawal symptoms as measured by the Clinical Opiate Withdrawal Scale (COWS). Scale 0-59, with the higher score representing greater withdrawal severity.
Time frame: Induction Phase: 1-30 days
Secondary
Mean of Individual Participant's Opioid Withdrawal Measured by Subjective Opioid Withdrawal Scale (SOWS) During Induction Phase
Opioid withdrawal symptoms as measured by the Subjective Opioid Withdrawal Scale (SOWS). Scale 0-64, with the higher score representing greater withdrawal severity.
Time frame: Induction Phase: 1-30 days
Secondary
Mean of Individual Participant's Opioid Withdrawal Measured by Subjective Opioid Withdrawal Scale (SOWS) During Post-induction Weeks 1 Through 4
Opioid withdrawal symptoms as measured by the Subjective Opioid Withdrawal Scale (SOWS). Scale 0-64, with the higher score representing greater withdrawal severity.
Time frame: Post Induction Phase: 1 - 4 weeks
Secondary
Number of Medical Visits and Therapy Completed During Follow up Treatment.
Engagement with medical visits and therapy (based on medical management log, XR- NTX dose log, Psychosocial log).
Time frame: Post Induction Phase: 1 - 8 weeks
Secondary
Percent of Participants Positive for Cocaine, Sedatives, Alcohol, Cannabis, and Tobacco Using Urine Drug Screens at Week 4 and 8
Use of alcohol and other drugs of abuse (e.g., cocaine, other stimulants, cannabis, benzodiazepines), by urine drug screens.
Time frame: Post Induction Phase: Week 4 and Week 8
Secondary
Percent of Participants Positive for Cocaine, Sedatives, Alcohol, Cannabis, and Tobacco Using Weekly TLFB During Eight Weeks of Post- Induction
Use of alcohol and other drugs of abuse (e.g., cocaine, other stimulants, cannabis, benzodiazepines), by self-report
Time frame: Post Induction Phase: 1 - 8 weeks
Secondary
Percent of Participants Positive for Opioids Using Urine Drug Screens at Week 4 and 8
Opioid abstinence, as measured by the proportion of opioid-positive urine tests.
Time frame: Post Induction Phase: Week 4 and Week 8
Secondary
Percent of Participants Positive for Opioids Using Weekly TLFB During Eight Weeks of Post-induction
Opioid abstinence, as measured by the Timeline Followback (TLFB) (self-report days using opioids)
Time frame: Post Induction Phase: 1 - 8 weeks
Secondary
Percent of Patients Reporting Continued Treatment With Medication for Opioid Use Disorder (MOUD) at Week 8
Use of medication for opioid use disorder (MOUD) as measured by patient self-report on Timeline Followback (TLFB).
Time frame: Post Induction Phase: Week 8
Secondary
Proportion of Participants That Receive Second and Third Injection of XR-NTX (at 1 Month and 2 Months, From First Injection)
Retention in the trial to receive the second and the third XR-NTX injections.
Time frame: Post Induction Phase: Week 4 and Week 8