Trial Outcomes & Findings for Addiction Treatment in Russia: Oral vs. Naltrexone Implant (NCT NCT00218426)

Last Updated: 2019-03-18

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

306 participants

Primary outcome timeframe

6 months

Results posted on

2019-03-18

Participant Flow

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.

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.

Participant milestones

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

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Addiction Treatment in Russia: Oral vs. Naltrexone Implant

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 6 months

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

Outcome measures

Outcome measures
Measure	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant n=102 Participants Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo n=102 Participants naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant n=102 Participants ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Retention Without Relapse to Heroin Addiction (Measured at Month 6)	54 Participants	16 Participants	11 Participants

SECONDARY outcome

Timeframe: 6 months

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

Outcome measures

Outcome measures
Measure	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant n=102 Participants Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo n=102 Participants naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant n=102 Participants ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Number of Subjects Who Dropped Out of Treatment	54 participants	16 participants	11 participants

SECONDARY outcome

Timeframe: 6 months

Population: missing = positive; results negative for opioids

missed urine tests were imputed to be positive for opiates

Outcome measures

Outcome measures
Measure	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant n=1428 urine tests Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo n=1428 urine tests naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant n=1428 urine tests ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Positive Opioid Urine Test	.427 urine tests Interval 0.4 to 0.45	.636 urine tests Interval 0.6 to 0.66	.341 urine tests Interval 0.32 to 0.37

SECONDARY outcome

Timeframe: 6 months

use of alcohol grams per day

Outcome measures

Outcome measures
Measure	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant n=102 Participants Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo n=102 Participants naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant n=102 Participants ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Use of Alcohol	10.2 grams per day Standard Deviation 1.7	9.0 grams per day Standard Deviation 1.7	9.6 grams per day Standard Deviation 1.6

SECONDARY outcome

Timeframe: 6 months

Population: mean of composite score

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.

Outcome measures

Outcome measures
Measure	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant n=102 Participants Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo n=102 Participants naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant n=102 Participants ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Composite Score of Psychiatric Problems	0.19 composite score Standard Deviation 0.02	0.15 composite score Standard Deviation 0.02	0.18 composite score Standard Deviation 0.02

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant n=102 Participants Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo n=102 Participants naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant n=102 Participants ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
HIV Risk (Baseline)	8.1 score on a scale Standard Deviation 0.44	8.0 score on a scale Standard Deviation 0.47	8.7 score on a scale Standard Deviation 0.49

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant n=102 Participants Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo n=102 Participants naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant n=102 Participants ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Global Assessment Form (GAF)	62.8 score on a scale Standard Deviation 0.7	64.7 score on a scale Standard Deviation 0.8	62.5 score on a scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant n=102 Participants Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo n=102 Participants naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant n=102 Participants ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Amphetamine Drug Use	6 Participants	12 Participants	18 Participants

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant n=102 Participants Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo n=102 Participants naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant n=102 Participants ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Cocaine Drug Use	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant n=102 Participants Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo n=102 Participants naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant n=102 Participants ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Marijuana Drug Use	22 Participants	35 Participants	25 Participants

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant n=102 Participants Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo n=102 Participants naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant n=102 Participants ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Benzodiazepine Drug Use	10 Participants	15 Participants	9 Participants

Adverse Events

ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant n=102 participants at risk Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo n=102 participants at risk naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant n=102 participants at risk ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Endocrine disorders cholecystectomy	0.00% 0/102 • 3 Years 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.	0.00% 0/102 • 3 Years 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.	0.98% 1/102 • Number of events 1 • 3 Years 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.

Other adverse events

Other adverse events
Measure	ON + DNIP, Oral Naltrexone + Depot Placebo Naltrexone Implant n=102 participants at risk Oral naltrexone Oral naltrexone: oral naltrexone 50 mg/day DNIP Depot Placebo Naltrexone Implant	DNI + ONP , Naltrexone Implant + Oral Naltrexone Placebo n=102 participants at risk naltrexone implant naltrexone implant: The implant is 1000 mg naltrexone ONP oral naltrexone placebo tablet	ONP + DNIP, Oral Placebo Naltrexone and Depot Placebo Implant n=102 participants at risk ONP daily placebo oral naltrexone monthly placebo depot naltrexone implant
Nervous system disorders headache	0.98% 1/102 • Number of events 1 • 3 Years 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.	0.00% 0/102 • 3 Years 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.	0.00% 0/102 • 3 Years 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.
Nervous system disorders drowsiness	0.00% 0/102 • 3 Years 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.	2.0% 2/102 • Number of events 2 • 3 Years 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.	0.00% 0/102 • 3 Years 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.
Gastrointestinal disorders nausea	0.98% 1/102 • Number of events 1 • 3 Years 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.	3.9% 4/102 • Number of events 4 • 3 Years 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.	2.0% 2/102 • Number of events 2 • 3 Years 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.
Cardiac disorders high blood pressure	0.00% 0/102 • 3 Years 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.	0.00% 0/102 • 3 Years 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.	0.00% 0/102 • 3 Years 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.
Hepatobiliary disorders increased liver enzyme	0.00% 0/102 • 3 Years 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.	2.0% 2/102 • Number of events 2 • 3 Years 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.	0.00% 0/102 • 3 Years 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.
Respiratory, thoracic and mediastinal disorders bronchitis	2.0% 2/102 • Number of events 2 • 3 Years 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.	0.00% 0/102 • 3 Years 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.	0.00% 0/102 • 3 Years 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.
Surgical and medical procedures local site reaction	2.0% 2/102 • Number of events 2 • 3 Years 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.	8.8% 9/102 • Number of events 9 • 3 Years 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.	0.98% 1/102 • Number of events 1 • 3 Years 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.

Additional Information

Dr. George E Woody

University of Pennsylvania

Phone: 215-746-7702

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	ONP + DNI n=102 Participants 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	ON + DNIP n=102 Participants Oral naltrexone 50 mg + Depot Naltrexone placebo Implant oral naltrexone: oral naltrexone 50 mg/day depot placebo implant: placebo implant resembles active medication	ONP + DNIP n=102 Participants Oral placebo naltrexone + placebo naltrexone implant placebo oral tablet: placebo oral tablet resembles active medication depot placebo implant: placebo implant resembles active medication	Total n=306 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	102 Participants n=5 Participants	102 Participants n=7 Participants	102 Participants n=5 Participants	306 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	28.0 years n=5 Participants	27.9 years n=7 Participants	28.7 years n=5 Participants	28.2 years n=4 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	28 Participants n=7 Participants	28 Participants n=5 Participants	84 Participants n=4 Participants
Sex: Female, Male Male	74 Participants n=5 Participants	74 Participants n=7 Participants	74 Participants n=5 Participants	222 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	102 Participants n=5 Participants	102 Participants n=7 Participants	102 Participants n=5 Participants	306 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	102 Participants n=5 Participants	102 Participants n=7 Participants	102 Participants n=5 Participants	306 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment Russia	102 participants n=5 Participants	102 participants n=7 Participants	102 participants n=5 Participants	360 participants n=4 Participants