Addiction Treatment in Russia: Oral vs. Naltrexone Implant

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT00218426
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH), St. Petersburg State Pavlov Medical University (Other)
• Enrollment: 306
• Locations: 2
• Arms: 3
• Actual Duration (Months): 52.1
• Patients Per Site: 153
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief Summary

Heroin addiction is a growing problem in Russia; individuals who enter heroin addiction treatment often relapse. Therefore, effective heroin addiction treatments are necessary to prevent relapse. The purpose of this study is to compare oral naltrexone with a naltrexone implant that provides opioid blockade for two months in preventing relapse to heroin addiction in St. Petersburg, Russia.

Condition or Disease	Intervention/Treatment	Phase
Heroin Dependence; Opioid-Related Disorders	Drug: naltrexone implant; Drug: oral naltrexone; Drug: oral placebo naltrexone; Drug: placebo implant	Phase 2/Phase 3

Detailed Description

The usual treatment of heroin addiction in Russia involves detoxification and 2-4 weeks of rehabilitation with referral to outpatient follow-up. Though most patients complete inpatient treatment, few keep follow-up appointments and relapse rates are high. More effective therapies are needed, especially in view of the epidemic of heroin addiction that has resulted in the spread of HIV and other infectious diseases. A recently-completed study of 52 patients randomized to oral naltrexone (ON) or oral naltrexone placebo (ONP) has shown efficacy in preventing relapse and reducing HIV risk but dropout was a problem with only 44% of ON patients proven to have not relapsed by 6 months (as compared to 16% of ONP patients). A larger study of 280 patients randomized to ON or ONP replicated these results and found some indication that adding an selective serotonin reuptake inhibitor (SSRI) to naltrexone may improve its efficacy in women, probably because they tend to have higher levels of psychiatric symptoms than men.

We think that retention and outcome can be improved by using a longer acting naltrexone preparation, and in this study we propose to compare ON with a depot naltrexone implant (DNI) that is manufactured and approved for use in Russia, and provides opioid blockade for 8-10 weeks. We will use a placebo-controlled, double-blind/double-dummy design since a placebo-controlled trial is required by the Russian equivalent of our FDA as a condition for testing a pharmacotherapy. Participants will be male and female heroin addicts who have been detoxified in addiction treatment hospitals or outpatient settings in St. Petersburg and have a family member willing and able to supervise medication adherence and facilitate follow-up. After giving informed consent and confirming the absence of physiologic dependence, 306 patients will be randomly assigned to a 6-month treatment in one of three groups of 102 each: oral naltrexone (ON) + depot naltrexone implant placebo (DNIP); oral naltrexone placebo (ONP)

• depot naltrexone implant (DNI); or ONP + DNIP. All patients will receive biweekly clinical management/adherence enhancement counseling. Assessments will be done at baseline, at each biweekly appointment during the 6-months of medication treatment, and at 3 and 6 months following the end of study medication. Primary outcome will be the relapse free proportion at months 1-6; secondary outcomes will be time to dropout, opioid positive urines, HIV risk, use of alcohol and other drugs, psychiatric symptoms, and other measures of overall adjustment. We hypothesize that outcomes will be better with DNI than ON, and that each will be more effective than placebo.

Study Design

• Study Type: Interventional
• Actual Enrollment: 306 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Addiction Treatment in Russia: Oral and Depot Naltrexone
• Actual Study Start Date: Jul 1, 2006
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Nov 4, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: ONP + DNI Oral naltrexone placebo (ONP) + Depot Naltrexone Implant (DNI) 1000 mg	Drug: naltrexone implant; naltrexone implant is 1000 mg naltrexone; Other Names: DNI ; Drug: oral placebo naltrexone; oral placebo naltrexone resembles active medication; Other Names: ONP
Active Comparator: ON + DNIP Oral naltrexone (ON) 50 mg + Depot Naltrexone placebo Implant (DNIP)	Drug: oral naltrexone; oral naltrexone 50 mg/day; Other Names: ON ; Drug: placebo implant; placebo implant resembles active medication; Other Names: DNIP
Placebo Comparator: ONP + DNIP Oral placebo naltrexone + placebo naltrexone implant	Drug: oral placebo naltrexone; oral placebo naltrexone resembles active medication; Other Names: ONP ; Drug: placebo implant; placebo implant resembles active medication; Other Names: DNIP

Outcome Measures

Primary Outcome Measures

1. Retention Without Relapse to Heroin Addiction (Measured at Month 6) [6 months]

   Survival analysis (Kaplan-Meier survival functions with log-rank Cox-Mantel criteria for group comparison was used to determine the primary outcome of retention, defined as not missing 2 consecutive counseling sessions and not having a relapse. Because this outcome combined patients who failed to keep appointments with those who kept appointments but relapsed, the proportion of non-survivors attributable to proven relapse.

Secondary Outcome Measures

1. Number of Subjects Who Dropped Out of Treatment [6 months]

   Kaplan-Meier survival curves for the event of subjects who dropped out of treatment

2. Positive Opioid Urine Test [6 months]

   missed urine tests were imputed to be positive for opiates

3. Use of Alcohol [6 months]

   use of alcohol grams per day

4. Composite Score of Psychiatric Problems [6 months]

   composite score is a decimal score; with 0 = no problems, 1 = the most problems based on the Addiction Severity Index composite score of 11 indexed questions.

5. HIV Risk (Baseline) [baseline]

   The Risk Assessment Behavior (RAB), is an HIV risk Scale. The Total Score is scored by adding the values that correspond to the responses selected by the subject for the items asked. This highest total score is 40 (highest risk), and the lowest score = 0 (no risk). This assessment has 2 Subsections: 1) Drug Risk = 8 questions (lowest Drug Risk score = 0 (no risk), and highest drug risk score = 22 =(greatest risk), 2) 10 Sex Risk questions: scores are 0 = no risk, and 18 = highest risk). Total RAB Score = Drug Risk Total + Sex Risk Total (0 = no risk, 40 = highest). See: Risk Assessment Battery (RAB) Scoring System, https://www.med.upenn.edu/hiv/assets/user-content/.../RABScoringv2.112.21.95.doc

6. Global Assessment Form (GAF) [baseline]

   Assessment of overall psychiatric function comprises Axis V in the DSM-IV (DSM-IV, 1994). GAF scores range from 0 to 100. A reasonably well-functioning person will score above 70; serious impairment is below 50.

7. Amphetamine Drug Use [baseline]

   Number of subjects who used Amphetamine in the past 90 days at baseline as measured by the TimeLine Follow-back Form (TLFB) . The TLFB is an instrument that assesses substance use over a specified period of time (Sobel & Sobel, 1992).

8. Cocaine Drug Use [baseline]

   Number of subjects with cocaine drug use in the past 90 days at baseline as measured by the TimeLine Follow-back Form (TLFB) . The TLFB is an instrument that assesses substance use over a specified period of time (Sobel & Sobel, 1992).

9. Marijuana Drug Use [baseline]

   Number of subjects with Marijuana use in the past 90 days at baseline as measured by the TimeLine Follow-back Form (TLFB) . The TLFB is an instrument that assesses substance use over a specified period of time (Sobel & Sobel, 1992).

10. Benzodiazepine Drug Use [baseline]

    Number of subjects with benzodiazepine drug use in the past 90 days at baseline as measured by the TimeLine Follow-back Form (TLFB) . The TLFB is an instrument that assesses substance use over a specified period of time (Sobel & Sobel, 1992).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Current opioid dependence

• Recently completed opioid detoxification

Exclusion Criteria:

• Serious medical or psychiatric condition requiring immediate hospitalization or that would make participation in the study hazardous

• Planning to leave the study area within the 12 months following study entry

• Imminent incarceration

• Pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104 6178
2	Pavlov Medical University	St. Petersburg		Russian Federation	197022

Sponsors and Collaborators

• University of Pennsylvania
• National Institute on Drug Abuse (NIDA)
• St. Petersburg State Pavlov Medical University

Investigators

• Principal Investigator: George Woody, MD, University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT00218426
• Other Study ID Numbers: NIDA-17317-1; R01DA017317; R01-17317-1; DPMC
• First Posted: Sep 22, 2005
• Last Update Posted: Mar 18, 2019
• Last Verified: Feb 1, 2019

• Additional relevant MeSH terms: Opioid-Related Disorders; Heroin Dependence; Naltrexone

Study Results

Participant Flow

Recruitment Details	Subjects (SS) are from Leningrad Regional Alcoholism and Substance Abuse Treatment Center, Leningrad Region; and St. Petersburg City Alcoholism and Substance Abuse Treatment Center, screened for detoxification and if met study criteria and interested were referred to study on day of discharge. First SS admitted on 7/31/06, last visit was 1/4/09.
Pre-assignment Detail	SS were opioid dependent with physiological features for at least 1 year, negative urine for opioids, had ability to give informed consent, not on psychotropic medication, if female, not pregnant, could provide at least 1 relative contact, no significant lab abnormality, and not major psych disorder.

Arm/Group Title	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant
Arm/Group Description	Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Period Title: Overall Study
STARTED	102	102	102
COMPLETED	54	16	11
NOT COMPLETED	48	86	91

Baseline Characteristics

Arm/Group Title	ONP + DNI	ON + DNIP	ONP + DNIP	Total
Arm/Group Description	Oral naltrexone placebo + Depot Naltrexone Implant 1000 mg naltrexone implant: depot implant is 1000 mg naltrexone placebo oral tablet: placebo oral tablet resembles active medication	Oral naltrexone 50 mg + Depot Naltrexone placebo Implant oral naltrexone: oral naltrexone 50 mg/day depot placebo implant: placebo implant resembles active medication	Oral placebo naltrexone + placebo naltrexone implant placebo oral tablet: placebo oral tablet resembles active medication depot placebo implant: placebo implant resembles active medication	Total of all reporting groups
Overall Participants	102	102	102	306
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	102 100%	102 100%	102 100%	306 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	28.0	27.9	28.7	28.2
Sex: Female, Male (Count of Participants)
Female	28 27.5%	28 27.5%	28 27.5%	84 27.5%
Male	74 72.5%	74 72.5%	74 72.5%	222 72.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	102 100%	102 100%	102 100%	306 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	102 100%	102 100%	102 100%	306 100%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Russia	102 100%	102 100%	102 100%	360 117.6%

Outcome Measures

1. Primary Outcome

Title	Retention Without Relapse to Heroin Addiction (Measured at Month 6)
Description	Survival analysis (Kaplan-Meier survival functions with log-rank Cox-Mantel criteria for group comparison was used to determine the primary outcome of retention, defined as not missing 2 consecutive counseling sessions and not having a relapse. Because this outcome combined patients who failed to keep appointments with those who kept appointments but relapsed, the proportion of non-survivors attributable to proven relapse.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Subjects who remained in treatment without relapse. remaining in treatment = 6 months manualized clinical counseling, plus medication.

Arm/Group Title	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant
Arm/Group Description	Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Measure Participants	102	102	102
Count of Participants [Participants]	54 52.9%	16 15.7%	11 10.8%

2. Secondary Outcome

Title	Number of Subjects Who Dropped Out of Treatment
Description	Kaplan-Meier survival curves for the event of subjects who dropped out of treatment
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant
Arm/Group Description	Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Measure Participants	102	102	102
Number [participants]	54 52.9%	16 15.7%	11 10.8%

3. Secondary Outcome

Title	Positive Opioid Urine Test
Description	missed urine tests were imputed to be positive for opiates
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

missing = positive; results negative for opioids

Arm/Group Title	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant
Arm/Group Description	Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Measure Participants	102	102	102
Measure urine tests	1428	1428	1428
Number (95% Confidence Interval) [urine tests]	.427	.636	.341

4. Secondary Outcome

Title	Use of Alcohol
Description	use of alcohol grams per day
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant
Arm/Group Description	Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Measure Participants	102	102	102
Mean (Standard Deviation) [grams per day]	10.2 (1.7)	9.0 (1.7)	9.6 (1.6)

5. Secondary Outcome

Title	Composite Score of Psychiatric Problems
Description	composite score is a decimal score; with 0 = no problems, 1 = the most problems based on the Addiction Severity Index composite score of 11 indexed questions.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

mean of composite score

Arm/Group Title	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant
Arm/Group Description	Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Measure Participants	102	102	102
Mean (Standard Deviation) [composite score]	0.19 (0.02)	0.15 (0.02)	0.18 (0.02)

6. Secondary Outcome

Title	HIV Risk (Baseline)
Description	The Risk Assessment Behavior (RAB), is an HIV risk Scale. The Total Score is scored by adding the values that correspond to the responses selected by the subject for the items asked. This highest total score is 40 (highest risk), and the lowest score = 0 (no risk). This assessment has 2 Subsections: 1) Drug Risk = 8 questions (lowest Drug Risk score = 0 (no risk), and highest drug risk score = 22 =(greatest risk), 2) 10 Sex Risk questions: scores are 0 = no risk, and 18 = highest risk). Total RAB Score = Drug Risk Total + Sex Risk Total (0 = no risk, 40 = highest). See: Risk Assessment Battery (RAB) Scoring System, https://www.med.upenn.edu/hiv/assets/user-content/.../RABScoringv2.112.21.95.doc
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant
Arm/Group Description	Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Measure Participants	102	102	102
Mean (Standard Deviation) [score on a scale]	8.1 (0.44)	8.0 (0.47)	8.7 (0.49)

7. Secondary Outcome

Title	Global Assessment Form (GAF)
Description	Assessment of overall psychiatric function comprises Axis V in the DSM-IV (DSM-IV, 1994). GAF scores range from 0 to 100. A reasonably well-functioning person will score above 70; serious impairment is below 50.
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant
Arm/Group Description	Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Measure Participants	102	102	102
Mean (Standard Deviation) [score on a scale]	62.8 (0.7)	64.7 (0.8)	62.5 (0.9)

8. Secondary Outcome

Title	Amphetamine Drug Use
Description	Number of subjects who used Amphetamine in the past 90 days at baseline as measured by the TimeLine Follow-back Form (TLFB) . The TLFB is an instrument that assesses substance use over a specified period of time (Sobel & Sobel, 1992).
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant
Arm/Group Description	Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Measure Participants	102	102	102
Count of Participants [Participants]	6 5.9%	12 11.8%	18 17.6%

9. Secondary Outcome

Title	Cocaine Drug Use
Description	Number of subjects with cocaine drug use in the past 90 days at baseline as measured by the TimeLine Follow-back Form (TLFB) . The TLFB is an instrument that assesses substance use over a specified period of time (Sobel & Sobel, 1992).
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ONP + DNI	ON + DNIP	ONP + DNIP
Arm/Group Description	Oral naltrexone placebo (ONP) + Depot Naltrexone Implant (DNI) 1000 mg naltrexone implant: naltrexone implant is 1000 mg naltrexone oral placebo naltrexone: oral placebo naltrexone resembles active medication	Oral naltrexone (ON) 50 mg + Depot Naltrexone placebo Implant (DNIP) oral naltrexone: oral naltrexone 50 mg/day placebo implant: placebo implant resembles active medication	Oral placebo naltrexone + placebo naltrexone implant oral placebo naltrexone: oral placebo naltrexone resembles active medication placebo implant: placebo implant resembles active medication
Measure Participants	102	102	102
Count of Participants [Participants]	0 0%	0 0%	0 0%

10. Secondary Outcome

Title	Marijuana Drug Use
Description	Number of subjects with Marijuana use in the past 90 days at baseline as measured by the TimeLine Follow-back Form (TLFB) . The TLFB is an instrument that assesses substance use over a specified period of time (Sobel & Sobel, 1992).
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant
Arm/Group Description	Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Measure Participants	102	102	102
Count of Participants [Participants]	22 21.6%	35 34.3%	25 24.5%

11. Secondary Outcome

Title	Benzodiazepine Drug Use
Description	Number of subjects with benzodiazepine drug use in the past 90 days at baseline as measured by the TimeLine Follow-back Form (TLFB) . The TLFB is an instrument that assesses substance use over a specified period of time (Sobel & Sobel, 1992).
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant
Arm/Group Description	Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Measure Participants	102	102	102
Count of Participants [Participants]	10 9.8%	15 14.7%	9 8.8%

Adverse Events

Time Frame	3 Years
Adverse Event Reporting Description	An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product. The event need not have a causal relationship to the treatment. Normal withdrawal is not considered an adverse event.
Arm/Group Title	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant		DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo		ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant
Arm/Group Description	Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant		naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet		ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
All Cause Mortality
	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant		DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo		ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/102 (0%)		0/102 (0%)		0/102 (0%)
Serious Adverse Events
	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant		DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo		ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/102 (0%)		0/102 (0%)		1/102 (1%)
Endocrine disorders
cholecystectomy	0/102 (0%)	0	0/102 (0%)	0	1/102 (1%)	1
Other (Not Including Serious) Adverse Events
	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant		DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo		ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/102 (5.9%)		17/102 (16.7%)		3/102 (2.9%)
Cardiac disorders
high blood pressure	0/102 (0%)	0	0/102 (0%)	0	0/102 (0%)	0
Gastrointestinal disorders
nausea	1/102 (1%)	1	4/102 (3.9%)	4	2/102 (2%)	2
Hepatobiliary disorders
increased liver enzyme	0/102 (0%)	0	2/102 (2%)	2	0/102 (0%)	0
Nervous system disorders
headache	1/102 (1%)	1	0/102 (0%)	0	0/102 (0%)	0
drowsiness	0/102 (0%)	0	2/102 (2%)	2	0/102 (0%)	0
Respiratory, thoracic and mediastinal disorders
bronchitis	2/102 (2%)	2	0/102 (0%)	0	0/102 (0%)	0
Surgical and medical procedures
local site reaction	2/102 (2%)	2	9/102 (8.8%)	9	1/102 (1%)	1

Limitations/Caveats

Limitations include limited amount of data on patients who did not remain in treatment, thus making it difficult to obtain more accurate information on the proportions with relapse at 9- and 12- month follow-ups and other secondary outcomes.

More Information

Certain Agreements

Principal Investigators are NOT 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.