Trial Outcomes & Findings for Drug Treatment Combined With Drug and Risk Reduction Counseling to Prevent of HIV Infection and Death Among Injection Drug Users (NCT NCT00270257)
NCT ID: NCT00270257
Last Updated: 2021-11-05
Results Overview
The primary endpoint for the study was cumulative HIV infection or death after a second year of follow-up (i.e. at week 104), one year after completion of the treatment phase, designed to test a durable intervention effect.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
1251 participants
Primary outcome timeframe
For visits up to week 104
Results posted on
2021-11-05
Participant Flow
The sites were selected based on prior HIV incidence rates among opiate injectors. At the first scheduled interim analyses, when 25% of the participants had completed 104 weeks on study, the Data Safety Monitoring Board (DSMB) halted the study due to futility as a result of lower than anticipated HIV incidence rates.
The study represented the first use of buprenorphine-naloxone as a treatment for opiate dependence in each community, thus implementation of the study and recruitment of participants included a significant effort devoted to community engagement and education. Each site had an active community advisory board (CAB).
Participant milestones
| Measure |
Long Term Medication Assisted Treatment (LT-MAT)
Participants will receive BUP/NX under the tongue daily for a maximum of three weeks(until dose stabilization) and then three times a week for 52 weeks in addition to weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52
Buprenorphine/Naloxone: Oral tablet
|
Short Term Medication Assisted Treatment (ST-MAT)
Participants will receive short-term BUP/NX; dosage and length of treatment will be determined by the investigator.Additionally, participants will undergo weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52.
Buprenorphine/Naloxone: Oral tablet
|
|---|---|---|
|
Overall Study
STARTED
|
623
|
628
|
|
Overall Study
Week 8
|
510
|
443
|
|
Overall Study
Week 26
|
460
|
440
|
|
Overall Study
Week 52
|
362
|
340
|
|
Overall Study
Week 78
|
283
|
285
|
|
Overall Study
Visit 104
|
211
|
204
|
|
Overall Study
COMPLETED
|
211
|
204
|
|
Overall Study
NOT COMPLETED
|
412
|
424
|
Reasons for withdrawal
| Measure |
Long Term Medication Assisted Treatment (LT-MAT)
Participants will receive BUP/NX under the tongue daily for a maximum of three weeks(until dose stabilization) and then three times a week for 52 weeks in addition to weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52
Buprenorphine/Naloxone: Oral tablet
|
Short Term Medication Assisted Treatment (ST-MAT)
Participants will receive short-term BUP/NX; dosage and length of treatment will be determined by the investigator.Additionally, participants will undergo weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52.
Buprenorphine/Naloxone: Oral tablet
|
|---|---|---|
|
Overall Study
Data Safety Monitoring Board (DSMB) halt
|
412
|
424
|
Baseline Characteristics
Drug Treatment Combined With Drug and Risk Reduction Counseling to Prevent of HIV Infection and Death Among Injection Drug Users
Baseline characteristics by cohort
| Measure |
Long Term Medication Assisted Treatment (LT-MAT)
n=623 Participants
Participants will receive BUP/NX under the tongue daily for a maximum of three weeks(until dose stabilization) and then three times a week for 52 weeks in addition to weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52
Buprenorphine/Naloxone: Oral tablet
|
Short Term Medication Assisted Treatment (ST-MAT)
n=627 Participants
Participants will receive short-term BUP/NX; dosage and length of treatment will be determined by the investigator.Additionally, participants will undergo weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52.
Buprenorphine/Naloxone: Oral tablet
|
Total
n=1250 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
|
33 years
n=5 Participants
|
34 years
n=7 Participants
|
34 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
49 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
99 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
574 Participants
n=5 Participants
|
577 Participants
n=7 Participants
|
1151 Participants
n=5 Participants
|
|
Region of Enrollment
China
|
522 participants
n=5 Participants
|
527 participants
n=7 Participants
|
1049 participants
n=5 Participants
|
|
Region of Enrollment
Thailand
|
101 participants
n=5 Participants
|
100 participants
n=7 Participants
|
201 participants
n=5 Participants
|
|
Years of Injection
|
7 Years
n=5 Participants
|
7 Years
n=7 Participants
|
7 Years
n=5 Participants
|
PRIMARY outcome
Timeframe: For visits up to week 104Population: Data Safety Monitoring Board (DSMB) halted the study on October 4, 2011 due to futility as a result of lower than anticipated HIV incidence rates. See participant flow section for the number of participants who completed visit up to 104 by July 31, 2012.
The primary endpoint for the study was cumulative HIV infection or death after a second year of follow-up (i.e. at week 104), one year after completion of the treatment phase, designed to test a durable intervention effect.
Outcome measures
| Measure |
Long Term Medication Assisted Treatment (LT-MAT)
n=477 Participants
Participants will receive BUP/NX under the tongue daily for a maximum of three weeks(until dose stabilization) and then three times a week for 52 weeks in addition to weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52
Buprenorphine/Naloxone: Oral tablet
|
Short Term Medication Assisted Treatment (ST-MAT)
n=470 Participants
Participants will receive short-term BUP/NX; dosage and length of treatment will be determined by the investigator.Additionally, participants will undergo weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52.
Buprenorphine/Naloxone: Oral tablet
|
|---|---|---|
|
Evidence of HIV-1 Infection or Death for Visits up to 104 Weeks
# of HIV infections
|
2 participants
|
5 participants
|
|
Evidence of HIV-1 Infection or Death for Visits up to 104 Weeks
# of Deaths
|
8 participants
|
9 participants
|
SECONDARY outcome
Timeframe: Measured through Week 104Population: Number of participants presented here applies to visit 104 for whom data available.
Urine drug screen were assessed monthly and semiannually.
Outcome measures
| Measure |
Long Term Medication Assisted Treatment (LT-MAT)
n=208 Participants
Participants will receive BUP/NX under the tongue daily for a maximum of three weeks(until dose stabilization) and then three times a week for 52 weeks in addition to weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52
Buprenorphine/Naloxone: Oral tablet
|
Short Term Medication Assisted Treatment (ST-MAT)
n=202 Participants
Participants will receive short-term BUP/NX; dosage and length of treatment will be determined by the investigator.Additionally, participants will undergo weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52.
Buprenorphine/Naloxone: Oral tablet
|
|---|---|---|
|
Number of Participants With Urinalysis Results Positive for Opiates
|
138 participants
|
141 participants
|
SECONDARY outcome
Timeframe: Measured through Week 104Population: Number of participants presented here applies to whom data available at week 104.
All participants completed interviewer-administered assessments of injection and non-injection drug use at baseline and at semi-annual visits.
Outcome measures
| Measure |
Long Term Medication Assisted Treatment (LT-MAT)
n=208 Participants
Participants will receive BUP/NX under the tongue daily for a maximum of three weeks(until dose stabilization) and then three times a week for 52 weeks in addition to weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52
Buprenorphine/Naloxone: Oral tablet
|
Short Term Medication Assisted Treatment (ST-MAT)
n=202 Participants
Participants will receive short-term BUP/NX; dosage and length of treatment will be determined by the investigator.Additionally, participants will undergo weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52.
Buprenorphine/Naloxone: Oral tablet
|
|---|---|---|
|
Self-report of Continued Injection Opiate Use in the Last 30 Days
|
102 participants
|
107 participants
|
SECONDARY outcome
Timeframe: Measured through Week 104Population: Number of participants presented here applies to whom data available at week 104.
Outcome measures
| Measure |
Long Term Medication Assisted Treatment (LT-MAT)
n=208 Participants
Participants will receive BUP/NX under the tongue daily for a maximum of three weeks(until dose stabilization) and then three times a week for 52 weeks in addition to weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52
Buprenorphine/Naloxone: Oral tablet
|
Short Term Medication Assisted Treatment (ST-MAT)
n=202 Participants
Participants will receive short-term BUP/NX; dosage and length of treatment will be determined by the investigator.Additionally, participants will undergo weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52.
Buprenorphine/Naloxone: Oral tablet
|
|---|---|---|
|
Number of Participants Reported Using Injection Equipment (Needles, Syringes, Cookers, Cottons, and Rinse Water) in the Prior 6 Months
|
23 participants
|
28 participants
|
SECONDARY outcome
Timeframe: Measured through Week 104Population: Number of participants presented here applies to whom data available at week 104.
Outcome measures
| Measure |
Long Term Medication Assisted Treatment (LT-MAT)
n=623 Participants
Participants will receive BUP/NX under the tongue daily for a maximum of three weeks(until dose stabilization) and then three times a week for 52 weeks in addition to weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52
Buprenorphine/Naloxone: Oral tablet
|
Short Term Medication Assisted Treatment (ST-MAT)
n=627 Participants
Participants will receive short-term BUP/NX; dosage and length of treatment will be determined by the investigator.Additionally, participants will undergo weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52.
Buprenorphine/Naloxone: Oral tablet
|
|---|---|---|
|
Self-reported Number of Injections in the Last Month
|
30 injections
Interval 6.0 to 60.0
|
30 injections
Interval 7.0 to 60.0
|
SECONDARY outcome
Timeframe: Measured through week 156 in Thailand and 104 weeks in ChinaPopulation: Baseline HCV antibody negative participants.
HCV antibody using two different HCV EIA assays (Ortho HCV antibody version 3.0 and Wantai HCV antibody assay) at baseline and between 26-156 weeks later. If both HCV EIA antibody assays were nonreactive, then the participant was considered not to be HCV infected. If either assay was reactive, then the Ortho HCV assay was repeated in duplicate. If two of 3 Ortho HCV assays were reactive, then the participant was considered to be HCV infected. Samples that were repeatedly reactive for HCV antibody at a follow-up visit were tested for HCV RNA by the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV assay. Not all participants had follow-up testing performed in China due to early closure of the study by the Data Safety Monitoring Board on account of futility due to a low HIV incidence (the primary study endpoint). Analysis was done separately for both countries
Outcome measures
| Measure |
Long Term Medication Assisted Treatment (LT-MAT)
n=132 Participants
Participants will receive BUP/NX under the tongue daily for a maximum of three weeks(until dose stabilization) and then three times a week for 52 weeks in addition to weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52
Buprenorphine/Naloxone: Oral tablet
|
Short Term Medication Assisted Treatment (ST-MAT)
n=78 Participants
Participants will receive short-term BUP/NX; dosage and length of treatment will be determined by the investigator.Additionally, participants will undergo weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52.
Buprenorphine/Naloxone: Oral tablet
|
|---|---|---|
|
Incident Hepatitis C Infections for Thailand and China
|
41 participants with HCV antibody
|
8 participants with HCV antibody
|
SECONDARY outcome
Timeframe: Measured through week 52Serum samples were tested at baseline and between 26-52 weeks later for Hepatitis B surface antigen (HBsAg) using a commercial enzyme immunoassay (EIA) (Abbott Murex HBsAg version 3.0). If the HBsAg test was initially non-reactive, then the participant was considered to be negative for HBsAg. If the HBsAg test was initially reactive, then it was repeated in duplicate. If at least two of 3 tests were reactive, then the participant was considered to be positive for HBsAg.
Outcome measures
| Measure |
Long Term Medication Assisted Treatment (LT-MAT)
n=607 Participants
Participants will receive BUP/NX under the tongue daily for a maximum of three weeks(until dose stabilization) and then three times a week for 52 weeks in addition to weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52
Buprenorphine/Naloxone: Oral tablet
|
Short Term Medication Assisted Treatment (ST-MAT)
n=55 Participants
Participants will receive short-term BUP/NX; dosage and length of treatment will be determined by the investigator.Additionally, participants will undergo weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52.
Buprenorphine/Naloxone: Oral tablet
|
|---|---|---|
|
Incident Hepatitis B Infections
|
9 participants with HBsAg
|
0 participants with HBsAg
|
Adverse Events
Long Term Medication Assisted Treatment (LT-MAT)
Serious events: 38 serious events
Other events: 0 other events
Deaths: 0 deaths
Short Term Medication Assisted Treatment (ST-MAT)
Serious events: 42 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Long Term Medication Assisted Treatment (LT-MAT)
n=623 participants at risk
Participants will receive BUP/NX under the tongue daily for a maximum of three weeks(until dose stabilization) and then three times a week for 52 weeks in addition to weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52
Buprenorphine/Naloxone: Oral tablet
|
Short Term Medication Assisted Treatment (ST-MAT)
n=628 participants at risk
Participants will receive short-term BUP/NX; dosage and length of treatment will be determined by the investigator.Additionally, participants will undergo weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52.
Buprenorphine/Naloxone: Oral tablet
|
|---|---|---|
|
Cardiac disorders
Aortic valve incompetence
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Cardiac disorders
Myocardial infarction
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Gastrointestinal disorders
Abdominal pain
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Gastrointestinal disorders
Food poisoning
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
|
General disorders
Death
|
0.48%
3/623 • Number of events 3
|
0.16%
1/628 • Number of events 1
|
|
General disorders
Drowning
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
|
Infections and infestations
Appendicitis
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Infections and infestations
Bone tuberculosis
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
|
Infections and infestations
Neurocysticercosis
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
|
Infections and infestations
Osteomyelitis
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Infections and infestations
Penicilliosis
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
0.16%
1/623 • Number of events 1
|
0.32%
2/628 • Number of events 2
|
|
Infections and infestations
Pneumonia staphylococcal
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Infections and infestations
Pulmonary tuberculosis
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Infections and infestations
Sepsis
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
|
Infections and infestations
Septic shock
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
|
Infections and infestations
Staphylococcal bacteraemia
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
|
Infections and infestations
Subcutaneous abscess
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
|
Infections and infestations
Tuberculous pleurisy
|
0.32%
2/623 • Number of events 2
|
0.00%
0/628
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Injury, poisoning and procedural complications
Cerebral haemorrhage traumatic
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Injury, poisoning and procedural complications
Concussion
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Injury, poisoning and procedural complications
Craniocerebral injury
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.00%
0/623
|
0.32%
2/628 • Number of events 2
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Injury, poisoning and procedural complications
Overdose
|
0.48%
3/623 • Number of events 3
|
0.80%
5/628 • Number of events 5
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Injury, poisoning and procedural complications
Stab wound
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Investigations
Alanine aminotransferase increased
|
1.9%
12/623 • Number of events 12
|
2.2%
14/628 • Number of events 14
|
|
Investigations
Blood bilirubin increased
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Investigations
Platelet count decreased
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic neoplasm malignant
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
|
Nervous system disorders
Loss of consciousness
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Psychiatric disorders
Depression
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Psychiatric disorders
Personality disorder
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Psychiatric disorders
Suicide attempt
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Henoch-Schonlein purpura
|
0.16%
1/623 • Number of events 1
|
0.00%
0/628
|
|
Vascular disorders
Vascular rupture
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
Other adverse events
| Measure |
Long Term Medication Assisted Treatment (LT-MAT)
n=623 participants at risk
Participants will receive BUP/NX under the tongue daily for a maximum of three weeks(until dose stabilization) and then three times a week for 52 weeks in addition to weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52
Buprenorphine/Naloxone: Oral tablet
|
Short Term Medication Assisted Treatment (ST-MAT)
n=628 participants at risk
Participants will receive short-term BUP/NX; dosage and length of treatment will be determined by the investigator.Additionally, participants will undergo weekly drug and risk reduction counseling for 12 weeks, and then every 4 weeks through Week 52.
Buprenorphine/Naloxone: Oral tablet
|
|---|---|---|
|
Injury, poisoning and procedural complications
chest Injury
|
0.00%
0/623
|
0.16%
1/628 • Number of events 1
|
Additional Information
Senior Statistical Analyst
Fred Hutchinson Cancer Research Center
Phone: 206-667-6167
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee All study abstracts and publications are subject to HPTN Publication and Public Information Policies and Clinical Trial Agreements between NIAID (DAIDS) and company collaborators. The publication or other disclosure can be delayed for up to thirty additional business days for manuscripts \& five business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER