NewHope: Naltrexone for Opioid Dependent Released Human Immunodeficiency Virus Positive (HIV+) Criminal Justice Populations

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01246401
• Collaborator: Baystate Medical Center (Other), National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 151
• Locations: 3
• Arms: 2
• Duration (Months): 64
• Patients Per Site: 50.3
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

Specific Aim: To conduct a randomized, placebo-controlled trial of extended release-naltrexone (XR-NTX) among Human Immunodeficiency Virus (HIV) infected prisoners meeting Diagnostic Statistical Manual IV (DSM-IV) criteria for opioid dependence who are transitioning from the structure of a correctional setting to the community.

Hypotheses:

1. XR-NTX will result in improved HIV clinical outcomes, including lower changes in HIV-1 RNA levels, higher CD4 counts and higher rates of retention in care.

2. XR-NTX will result in improved opioid treatment outcomes, including longer time to opioid relapse, lower addiction severity and lower craving for opioid.

3. XR-NTX will result in reduced drug- and sex-related HIV risk behaviors compared to the control group.

4. XR-NTX will result in decreased rates of reincarceration after 12 months of release to the community.

Condition or Disease	Intervention/Treatment	Phase
HIV; AIDS; Opioid Dependence; Drug Dependence	Drug: Extended-Release Naltrexone	Phase 1/Phase 2

Detailed Description

The specific aim for this study is to conduct a placebo-controlled trail (RCT) of XR-NTX among HIV+ persons in jails and prisons meeting DSM-IV criteria for opioid dependence who are transitioning to the community. HIV treatment outcomes (HIV-1 RNA levels, CD4 count, Highly Active Antiretroviral Therapy (HAART) adherence, retention in care), substance abuse (time to relapse to opioid use, % opioid negative urines, opioid craving), adverse side effects and HIV risk behavior (sexual and drug-related risks) outcomes will be compared in 150 recruited prisoners and jail detainees in Connecticut (CT) and Massachusetts (MA) who will be randomized 2:1 to either XR-NTX or placebo. The primary outcome of interest will be the proportion with a HIV-RNA <400 copies/mL at 6 months. Secondary outcomes include mean CD4 count, antiretroviral adherence, retention on HAART and in HIV care, HIV risk behaviors, time-to-relapse to opioid use, percent opioid negative urines, retention on d-NTX and HIV quality of life. Primary and secondary outcomes will be assessed for an additional 6 months after completion of the intervention. If this placebo-controlled trial of XR-NTX among released HIV+ criminal justice system (CJS) persons with opioid dependence demonstrates efficacy and safety, it is likely to become an evidence-based intervention to intervene with this extremely marginalized population in a way that will meet Healthy People 2010's goals to increase the quality and years of life, decrease health disparities particularly among minorities, break the cycle of addiction, reduce the numbers of people within the CJS and launch a number of new and innovative trials and second generation questions for future research. As such, the individual, our health care system and society have a high likelihood to benefit. This will not only be true for strategies here in the U.S., but may have even greater application for geographic areas where the interface between opioid disorders and HIV is even greater.

Study Design

• Study Type: Interventional
• Actual Enrollment: 151 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Naltrexone for Opioid Dependent Released Human Immunodeficiency Virus Positive (HIV+) Criminal Justice Populations
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Extended-Release Naltrexone Participants will receive intramuscular (IM) injections of Naltrexone once monthly for 6 months, the first injection being prior release	Drug: Extended-Release Naltrexone; Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg; Other Names: Naltrexone, depot Vivitrol
Placebo Comparator: Placebo Participants will receive IM injections of Placebo once monthly for 6 months, the first injection being prior release	Drug: Extended-Release Naltrexone; Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg; Other Names: Naltrexone, depot Vivitrol

Outcome Measures

Primary Outcome Measures

1. Participants Who Had Undetectable HIV-1 RNA Levels at Less Than 400 Copies/mL at Six Month [6 months]

   Baseline labs will be drawn while subject is in prison, one to three months prior to release. Additionally, labs will be drawn every 3 months for 1 year to monitor changes in HIV-1 RNA levels. Treatment time period was the first 6 months where the primary outcome data will be based on.

Secondary Outcome Measures

1. Particpants Who Had Undetectable HIV-1 RNA Levels at Less Than 50 Copies/mL [6 months]

   Baseline labs will be drawn while subject is in prison, one to three months prior to release. Additionally, labs will be drawn every 3 months for 1 year to monitor changes in HIV-1 RNA levels. Treatment time period was the first 6 months where the primary outcome data will be based on.

2. CD4 Cell Count (Cells/mL) [Baseline and 6 months]

   Baseline labs will be drawn while subject is in prison, one to three months prior to release. Additional labs will be drawn every 3 months for 1 year to monitor changes in CD4 levels.

3. Time to Opioid Relapse or End of Intervention [6 months]

   Measuring days to first relapse based on self reported opioids (heroin) use within the 6 month (180 days) intervention period. If participants had no follow-up visits, and thus no self reported opiate use, they were treated as missing. Those who did not relapse within the 6 month intervention period were treated as having 180 days until relapse.

4. Addiction Severity [baseline, and 6 months]

   The Addiction Severity Index (ASI) questionnaire will be used to assess addiction severity. The ASI composite scoreprovides reliable and valid measure of patient status in a particular module of interest which can then be usecompared at the beginning of treatment to the evaluation endpoint to note the improvement or lack thereof. In this assessment the drug composite score was calculated using algorithm by Treatment Research Institute. If the score increases then it shows increase in severity where as if it decreases then it shows decrease in severity for that measured module. The scale ranges from 0 to 1. The mean composite scores for drug use from baseline to 6 months were compared using Nonparametric test.

5. Craving for Opioids [6 months]

   Craving at baseline compared to 6 month. This is assessed through a self report scale rated 0 to 10; 0 meaning not craving and 10 meaning highest craving. Change in craving score was categorized as 1)no change between baseline and 6 month; 2)increased craving - baseline craving was reported lower than at 6 month; 3)decreased craving - baseline craving was reported higher than 6 month craving.

6. Antiretroviral Therapy (ART) Adherence 100% [6 months]

   Number of subjects with 100% adherence at 6 months measured using Visual Analogue Scale: 0% to 100%

7. Participants With Opiate Abstinence Via By Doing Urine Toxicology Test [6 month]

   Percent of subjects with no opiate use at 6 month. Missing data was treated as failure (opiate positive).

8. Opioid Abstinence at 6 Months for Those With More Than 4 Injections [6 months]

   Based on self reported opioids (heroin) use. All participants receiving Placebo as well as participants who received 3 or less XR-NTX injections were compared to those who receive 4 or more XR-NTX injection.

9. ART Adherence for 4 or More Injections XR-NTX Versus Placebo and 3 or Less Injections of XR-NTX [6 months]

   The arm/group number of the participants vary from the primary outcome because this is a treatment effect analysis. All client with missing data at 6 months were considered as failure - meaning - they had less than 100% ART adherence.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Meets DSM-IV criteria for opioid dependence

2. Age > 18 years

3. Confirmed HIV infection, either through positive HIV antibody or detectable HIV-1 RNA level.

4. Within the Connecticut Department of Corrections (CTDOC) or Hampden County Correctional Center (HCCC) and within 30 days of being released to the greater New Haven, Hartford or Springfield areas or within 30 days after release from CTDOC or HCCC.

5. No participation in pharmacotherapy trial in the previous 30 days

6. Not pregnant

Exclusion Criteria:

1. Unable to provide informed consent

2. Verbally or physically threatening to research staff

3. Unable to communicate in either English or Spanish

4. Pending trials for a felony

5. Liver failure (Childs-Pugh Class B or C Cirrhosis)

6. Grade IV Hepatitis (liver function tests > 10X normal)

7. Receiving opioid prescription narcotics or has pain syndrome necessitating future use of opioid prescription narcotics.

8. Receiving active methadone or buprenorphine/naloxone for the treatment of opioid dependency

9. Active opioid withdrawal (within 3-5 days since last opioid ingestion)

10. Pregnancy or unwilling to take contraceptives measures

11. Breast-feeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University	Hartford	Connecticut	United States	06106
2	Yale University	New Haven	Connecticut	United States	06519
3	Baystate Medical Center	Springfield	Massachusetts	United States	01103

Sponsors and Collaborators

• Yale University
• Baystate Medical Center
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Sandra A Springer, MD, Yale University
• Principal Investigator: Frederick L Altice, Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Di Paola A, Lincoln T, Skiest DJ, Desabrais M, Altice FL, Springer SA. Design and methods of a double blind randomized placebo-controlled trial of extended-release naltrexone for HIV-infected, opioid dependent prisoners and jail detainees who are transitioning to the community. Contemp Clin Trials. 2014 Nov;39(2):256-68. doi: 10.1016/j.cct.2014.09.002. Epub 2014 Sep 18.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT01246401
• Other Study ID Numbers: 1007007169; 1K02DA032322-01
• First Posted: Nov 23, 2010
• Last Update Posted: Mar 19, 2020
• Last Verified: Jun 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; HIV Seropositivity; Opioid-Related Disorders; Substance-Related Disorders; Naltrexone

Study Results

Participant Flow

Recruitment Details	151 subjects consented, 58 lost before randomization

Arm/Group Title	Extended-Release Naltrexone	Placebo
Arm/Group Description	Participants will receive intramuscular (IM) injections of Naltrexone once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg	Participants will receive IM injections of Placebo once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg
Period Title: Overall Study
STARTED	66	27
COMPLETED	66	27
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Extended-Release Naltrexone	Placebo	Total
Arm/Group Description	Participants will receive intramuscular (IM) injections of Naltrexone once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg	Participants will receive IM injections of Placebo once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg	Total of all reporting groups
Overall Participants	66	27	93
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.6 (8.3)	43.9 (7.8)	45.8 (8.2)
Sex: Female, Male (Count of Participants)
Female	11 16.7%	6 22.2%	17 18.3%
Male	55 83.3%	21 77.8%	76 81.7%
Housing status (Count of Participants)
Stable	23 34.8%	11 40.7%	34 36.6%
Unstable	19 28.8%	4 14.8%	23 24.7%
Homeless	24 36.4%	12 44.4%	36 38.7%
Currently prescribed ART (Count of Participants)
Count of Participants [Participants]	58 87.9%	24 88.9%	82 88.2%
Alcohol Use Severity (AUDIT score) (Count of Participants)
Abstinent or Low-Risk Drinking	42 63.6%	23 85.2%	65 69.9%
Hazardous Drinking	11 16.7%	2 7.4%	13 14%
Harmful Drinking	2 3%	0 0%	2 2.2%
Possible Dependence	10 15.2%	2 7.4%	12 12.9%
Missing	1 1.5%	0 0%	1 1.1%
Opioid craving (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	3.2 (3.6)	3.5 (3.8)	3.3 (3.6)
Years Reported use of substances (years) [Mean (Standard Deviation) ]
Alcohol	13.5 (15.2)	9.2 (11.6)	12.2 (14.3)
Cannabis	14 (14.3)	12.8 (12.5)	13.6 (13.7)
Cocaine	17.5 (11.4)	18.7 (8.6)	17.9 (10.6)
Heroin	20.1 (11.2)	18.4 (10.2)	19.6 (10.9)
Other Opioids	2.8 (7.2)	3.2 (5.4)	2.9 (6.7)

Outcome Measures

1. Primary Outcome

Title	Participants Who Had Undetectable HIV-1 RNA Levels at Less Than 400 Copies/mL at Six Month
Description	Baseline labs will be drawn while subject is in prison, one to three months prior to release. Additionally, labs will be drawn every 3 months for 1 year to monitor changes in HIV-1 RNA levels. Treatment time period was the first 6 months where the primary outcome data will be based on.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

A total of 80 participants had viral load data at 6 months (56 in XR-NTX group and 24 in Placebo group). The remaining 13 participants (10 in XR-NTX group and 3 in Placebo group) with missing viral load data at 6 months were considered as failure - meaning - having a viral load of 400 or more. Thus included into the final analysis.

Arm/Group Title	Extended-Release Naltrexone	Placebo
Arm/Group Description	Participants will receive intramuscular (IM) injections of Naltrexone once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg	Participants will receive IM injections of Placebo once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg
Measure Participants	66	27
Count of Participants [Participants]	45 68.2%	16 59.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Extended-Release Naltrexone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.431
	Comments
	Method	Welch's T Test
	Comments

2. Secondary Outcome

Title	Particpants Who Had Undetectable HIV-1 RNA Levels at Less Than 50 Copies/mL
Description	Baseline labs will be drawn while subject is in prison, one to three months prior to release. Additionally, labs will be drawn every 3 months for 1 year to monitor changes in HIV-1 RNA levels. Treatment time period was the first 6 months where the primary outcome data will be based on.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

A total of 80 participants had viral load data at 6 months (56 in XR-NTX group and 24 in Placebo group). The remaining 13 participants (10 in XR-NTX group and 3 in Placebo group) with missing viral load data at 6 months were considered as failure - meaning - having a viral load of 400 or more. Thus included into the final analysis.

Arm/Group Title	Extended-Release Naltrexone	Placebo
Arm/Group Description	Participants will receive intramuscular (IM) injections of Naltrexone once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg	Participants will receive IM injections of Placebo once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg
Measure Participants	66	27
Count of Participants [Participants]	40 60.6%	11 40.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Extended-Release Naltrexone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.087
	Comments
	Method	Welch's T Test
	Comments

3. Secondary Outcome

Title	CD4 Cell Count (Cells/mL)
Description	Baseline labs will be drawn while subject is in prison, one to three months prior to release. Additional labs will be drawn every 3 months for 1 year to monitor changes in CD4 levels.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

Data was collected via labs. At month 6, due to attrition, data was only available for a total of 46 subjects. These include, 14 in Placebo and 32 in Extended-Release Naltrexone. The mean and STD are presented below.

Arm/Group Title	Extended-Release Naltrexone	Placebo
Arm/Group Description	Participants will receive intramuscular (IM) injections of Naltrexone once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg	Participants will receive IM injections of Placebo once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg
Measure Participants	66	27
Baseline mean CD4 count	465.2 (273.8)	580.8 (336.8)
Month 6 mean CD4 count	462 (306.6)	485.6 (257.3)

4. Secondary Outcome

Title	Time to Opioid Relapse or End of Intervention
Description	Measuring days to first relapse based on self reported opioids (heroin) use within the 6 month (180 days) intervention period. If participants had no follow-up visits, and thus no self reported opiate use, they were treated as missing. Those who did not relapse within the 6 month intervention period were treated as having 180 days until relapse.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Data collected via Time Line Fall Back (TLFB). 15 in XR-NTX group and 4 in Placebo did not have data because of attrition - treated as missing. An additional 19 people in the treatment arm and 9 in placebo filled out the TLFB at 9 or 12 months, and this data was used to fill in missing information.

Arm/Group Title	Extended-Release Naltrexone	Placebo
Arm/Group Description	Participants will receive intramuscular (IM) injections of Naltrexone once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg	Participants will receive IM injections of Placebo once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg
Measure Participants	51	23
Median (Full Range) [days]	137	29

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Extended-Release Naltrexone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments	Wilcoxon one sided
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	Addiction Severity
Description	The Addiction Severity Index (ASI) questionnaire will be used to assess addiction severity. The ASI composite scoreprovides reliable and valid measure of patient status in a particular module of interest which can then be usecompared at the beginning of treatment to the evaluation endpoint to note the improvement or lack thereof. In this assessment the drug composite score was calculated using algorithm by Treatment Research Institute. If the score increases then it shows increase in severity where as if it decreases then it shows decrease in severity for that measured module. The scale ranges from 0 to 1. The mean composite scores for drug use from baseline to 6 months were compared using Nonparametric test.
Time Frame	baseline, and 6 months

Outcome Measure Data

Analysis Population Description

An additional subject's data from the experimental group was not collected at baseline. For the 6 months data, the total number of participants with completed assessment used for the analysis was 46 (31 in XR-NTX group and 15 in Placebo group).

Arm/Group Title	Extended-Release Naltrexone	Placebo
Arm/Group Description	Participants will receive intramuscular (IM) injections of Naltrexone once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg	Participants will receive IM injections of Placebo once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg
Measure Participants	65	27
baseline	0.37 (0.16)	0.42 (0.14)
6 month	0.12 (0.13)	0.16 (0.16)

6. Secondary Outcome

Title	Craving for Opioids
Description	Craving at baseline compared to 6 month. This is assessed through a self report scale rated 0 to 10; 0 meaning not craving and 10 meaning highest craving. Change in craving score was categorized as 1)no change between baseline and 6 month; 2)increased craving - baseline craving was reported lower than at 6 month; 3)decreased craving - baseline craving was reported higher than 6 month craving.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Data available at 6 month determined who was included into the analysis. In this case a total of 47 data points (those with both baseline and 6 month data points) were included into the analysis (32 Extended-Release Naltrexone and 15 Placebo).

Arm/Group Title	Extended-Release Naltrexone	Placebo
Arm/Group Description	Participants will receive intramuscular (IM) injections of Naltrexone once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg	Participants will receive IM injections of Placebo once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg
Measure Participants	32	15
No change	12 18.2%	7 25.9%
Increased craving at 6 mo	6 9.1%	3 11.1%
Decreased craving at 6 mo	14 21.2%	5 18.5%

7. Secondary Outcome

Title	Antiretroviral Therapy (ART) Adherence 100%
Description	Number of subjects with 100% adherence at 6 months measured using Visual Analogue Scale: 0% to 100%
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

56 participants with missing data were considered as failure - meaning - with adherence less than 100%, and included into the analysis.

Arm/Group Title	Extended-Release Naltrexone	Placebo
Arm/Group Description	Participants will receive intramuscular (IM) injections of Naltrexone once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg	Participants will receive IM injections of Placebo once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg
Measure Participants	66	27
Count of Participants [Participants]	25 37.9%	12 44.4%

8. Secondary Outcome

Title	Participants With Opiate Abstinence Via By Doing Urine Toxicology Test
Description	Percent of subjects with no opiate use at 6 month. Missing data was treated as failure (opiate positive).
Time Frame	6 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Extended-Release Naltrexone	Placebo
Arm/Group Description	Participants will receive intramuscular (IM) injections of Naltrexone once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg	Participants will receive IM injections of Placebo once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg
Measure Participants	66	27
NEG Opi at Day of Release	44 66.7%	17 63%
NEG Opi at 6 month	13 19.7%	5 18.5%

9. Secondary Outcome

Title	Opioid Abstinence at 6 Months for Those With More Than 4 Injections
Description	Based on self reported opioids (heroin) use. All participants receiving Placebo as well as participants who received 3 or less XR-NTX injections were compared to those who receive 4 or more XR-NTX injection.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Collected via Time Line Fall Back (TLFB). Total N analyzed is 74. 12 of the clients had initial or some TLFB data indicating relapse but were counted as lost at 6 months for outcome 4. 19 Clients did not have TLFB data or if they did within 6 month it did not indicate any relapse. These were treated as missing and not included in analysis.

Arm/Group Title	Placebo + Participants With 3 or Fewer XR-NTX Injections	4 or More XR-NTX Injections
Arm/Group Description	All participants receiving Placebo as well as participants who received 3 or less XR-NTX injections	All participants who received 4 or more XR-NTX injections
Measure Participants	58	16
Count of Participants [Participants]	18 27.3%	13 48.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Extended-Release Naltrexone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.03962
	Comments
	Method	Chi-squared
	Comments

10. Secondary Outcome

Title	ART Adherence for 4 or More Injections XR-NTX Versus Placebo and 3 or Less Injections of XR-NTX
Description	The arm/group number of the participants vary from the primary outcome because this is a treatment effect analysis. All client with missing data at 6 months were considered as failure - meaning - they had less than 100% ART adherence.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

All client with missing data at 6 months were considered as failure - meaning - they had less than 100% ART adherence.

Arm/Group Title	Placebo + Participants With 3 or Fewer XR-NTX Injections	4 or More XR-NTX Injections
Arm/Group Description	All participants receiving Placebo as well as participants who received 3 or less XR-NTX injections	All participants who received 4 or more XR-NTX injections
Measure Participants	77	16
Count of Participants [Participants]	23 34.8%	14 51.9%

Adverse Events

Arm/Group Title	Extended-Release Naltrexone		Placebo
Arm/Group Description	Participants will receive intramuscular (IM) injections of Naltrexone once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg		Participants will receive IM injections of Placebo once monthly for 6 months, the first injection being prior release Extended-Release Naltrexone: Extended-Release Naltrexone (Vivitrol), once a month by IM injection, for a total of 6 months. Dosage is 380mg
All Cause Mortality
	Extended-Release Naltrexone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Extended-Release Naltrexone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/66 (0%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	Extended-Release Naltrexone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/66 (19.7%)		4/27 (14.8%)
Blood and lymphatic system disorders
Signs of Edema	2/66 (3%)		2/27 (7.4%)
Gastrointestinal disorders
Nausea	1/66 (1.5%)		1/27 (3.7%)
Vomiting	1/66 (1.5%)		0/27 (0%)
Diarrhea	3/66 (4.5%)		0/27 (0%)
General disorders
Fatigue	6/66 (9.1%)		1/27 (3.7%)
Metabolism and nutrition disorders
Decreased Apetite	2/66 (3%)		1/27 (3.7%)
Increased Apetite	2/66 (3%)		1/27 (3.7%)
Musculoskeletal and connective tissue disorders
Immediate Injection Reaction	10/66 (15.2%)		2/27 (7.4%)
Nervous system disorders
Headache	5/66 (7.6%)		0/27 (0%)
Skin and subcutaneous tissue disorders
Injection Site Reaction	2/66 (3%)		0/27 (0%)
Skin and Soft Tissue Infection	2/66 (3%)		1/27 (3.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.