BRAVO: Buprenorphine to Improve HIV Care Engagement and Outcomes

• Sponsor: Oregon Health and Science University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01936857
• Collaborator: Hanoi Medical University (Other), Hennepin Healthcare Research Institute (Other)
• Enrollment: 281
• Locations: 6
• Arms: 2
• Actual Duration (Months): 45
• Patients Per Site: 46.8
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of this study is to compare two models of substance abuse treatment in Vietnam, and how they each affect HIV care. In Vietnam, the current model for treating people with HIV who are also dependent on opioids is to refer them to methadone maintenance treatment centers. The new model the protocol will study is treatment of HIV and opioid dependence with buprenorphine/naloxone and counseling in the HIV clinic.

Condition or Disease	Intervention/Treatment	Phase
HIV; Substance Related Disorders	Drug: Buprenorphine/naloxone; Drug: Methadone Maintenance Therapy	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 281 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Buprenorphine to Improve HIV Care Engagement and Outcomes: A Randomized Trial (BRAVO)
• Actual Study Start Date: Jul 1, 2015
• Actual Primary Completion Date: Mar 1, 2019
• Actual Study Completion Date: Apr 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Buprenorphine/naloxone Office based treatment of opioid dependence with buprenorphine/naloxone	Drug: Buprenorphine/naloxone; Buprenorphine/naloxone induction begins with a 2-4mg test dose followed by additional doses on the day of induction to relieve withdrawal symptoms, and then titrated to a maintenance dose between 8-24 mg/day over 1 to 3 days. Doses will be directly observed and occur daily. After a minimum of 2 weeks, dosing may be changed to 3 or 4 times per week, as determined clinically appropriate by the HIV clinic study physician. Dosing will remain flexible to a maximum dose of 24mg for daily dosing and 32mg for every other day dosing, as deemed clinically appropriate by the study physician.; Other Names: Suboxone
Active Comparator: Methadone Maintenance Therapy Referral to methadone maintenance therapy for treatment of opioid dependence.	Drug: Methadone Maintenance Therapy; Subjects randomized to methadone maintenance therapy (MMT) referral will meet with an HIV clinic case manager who will facilitate referral to MMT. Methadone dosing will be managed by MMT staff, who dispense methadone according to Ministry of Health guidelines for MMT.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With HIV Viral Suppression [12 months]

   HIV-1 RNA < 200 copies/mL

2. Participants With Heroin Use (Urine Drug Screen) [12 months]

3. Participants With Heroin Use (Self-report) [12 months]

Secondary Outcome Measures

1. Number of Participants in Receipt of Antiretroviral Therapy (ART) [12 months]

   Initiation of and retention on treatment with antiretroviral medications.

2. Number of Participants in Retention in HIV Care [12 months]

   HIV clinic visit in past 3 months

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• HIV positive

• Current moderate or severe Diagnostic and Statistical Manual (DSM-V) opioid use disorder

• Urine drug screen positive for opioids

• Interested in receiving treatment for opioid dependence

• Age at least 18 years old

• Willing to practice an effective method of birth control, if female

Exclusion Criteria:

• Known hypersensitivity to buprenorphine or naloxone

• aspartate aminotransferase (AST) & alanine aminotransferase (ALT) > 5x upper limit

• Currently pregnant or breastfeeding

• Serious medical or psychiatric illness in past 30 days (e.g. opportunistic infection, psychosis) that precludes safe participation in the opinion of study physician

• Methadone maintenance treatment within 30 days of consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bac Giang PAC OPC	Bac Giang		Vietnam
2	Dong Da OPC	Hanoi		Vietnam
3	Hoang Mai HIV Clinic	Hanoi		Vietnam
4	Long Bien	Hanoi		Vietnam
5	Tu Liem	Hanoi		Vietnam
6	Thanh Hoa PAC OPC	Thanh Hoa		Vietnam

Sponsors and Collaborators

• Oregon Health and Science University
• Hanoi Medical University
• Hennepin Healthcare Research Institute

Investigators

• Principal Investigator: Philip T Korthuis, MD, MPH, Oregon Health and Science University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 27, 2020

More Information

Publications

None provided.

• Responsible Party: P. Todd Korthuis, MD, Professor of Medicine, Oregon Health and Science University
• ClinicalTrials.gov Identifier: NCT01936857
• Other Study ID Numbers: 1R01DA037441_VNE; 1R01DA037441
• First Posted: Sep 6, 2013
• Last Update Posted: May 17, 2022
• Last Verified: Apr 1, 2022

• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Substance-Related Disorders; Buprenorphine; Methadone; Buprenorphine, Naloxone Drug Combination; Naloxone

Study Results

Participant Flow

Arm/Group Title	Buprenorphine/Naloxone	Methadone Maintenance Therapy
Arm/Group Description	Office based treatment of opioid dependence with buprenorphine/naloxone Buprenorphine/naloxone: Buprenorphine/naloxone induction begins with a 2-4mg test dose followed by additional doses on the day of induction to relieve withdrawal symptoms, and then titrated to a maintenance dose between 8-24 mg/day over 1 to 3 days. Doses will be directly observed and occur daily. After a minimum of 2 weeks, dosing may be changed to 3 or 4 times per week, as determined clinically appropriate by the HIV clinic study physician. Dosing will remain flexible to a maximum dose of 24mg for daily dosing and 32mg for every other day dosing, as deemed clinically appropriate by the study physician.	Referral to methadone maintenance therapy for treatment of opioid dependence. Methadone Maintenance Therapy: Subjects randomized to methadone maintenance therapy (MMT) referral will meet with an HIV clinic case manager who will facilitate referral to MMT. Methadone dosing will be managed by MMT staff, who dispense methadone according to Ministry of Health guidelines for MMT.
Period Title: Overall Study
STARTED	141	140
COMPLETED	107	115
NOT COMPLETED	34	25

Baseline Characteristics

Arm/Group Title	Buprenorphine/Naloxone	Methadone Maintenance Therapy	Total
Arm/Group Description	Office based treatment of opioid dependence with buprenorphine/naloxone Buprenorphine/naloxone: Buprenorphine/naloxone induction begins with a 2-4mg test dose followed by additional doses on the day of induction to relieve withdrawal symptoms, and then titrated to a maintenance dose between 8-24 mg/day over 1 to 3 days. Doses will be directly observed and occur daily. After a minimum of 2 weeks, dosing may be changed to 3 or 4 times per week, as determined clinically appropriate by the HIV clinic study physician. Dosing will remain flexible to a maximum dose of 24mg for daily dosing and 32mg for every other day dosing, as deemed clinically appropriate by the study physician.	Referral to methadone maintenance therapy for treatment of opioid dependence. Methadone Maintenance Therapy: Subjects randomized to methadone maintenance therapy (MMT) referral will meet with an HIV clinic case manager who will facilitate referral to MMT. Methadone dosing will be managed by MMT staff, who dispense methadone according to Ministry of Health guidelines for MMT.	Total of all reporting groups
Overall Participants	141	140	281
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.0 (5.8)	38.6 (6.4)	38.3 (6.1)
Sex: Female, Male (Count of Participants)
Female	5 3.5%	4 2.9%	9 3.2%
Male	136 96.5%	136 97.1%	272 96.8%
Race/Ethnicity, Customized (Count of Participants)
Kinh	139 98.6%	139 99.3%	278 98.9%
Other	2 1.4%	1 0.7%	3 1.1%
Region of Enrollment (participants) [Number]
Vietnam	141 100%	140 100%	281 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With HIV Viral Suppression
Description	HIV-1 RNA < 200 copies/mL
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Follow up viral suppression was not available for 50 buprenorphine group participants, and 33 of methadone group participants.

Arm/Group Title	Buprenorphine/Naloxone	Methadone Maintenance Therapy
Arm/Group Description	Office based treatment of opioid dependence with buprenorphine/naloxone Buprenorphine/naloxone: Buprenorphine/naloxone induction begins with a 2-4mg test dose followed by additional doses on the day of induction to relieve withdrawal symptoms, and then titrated to a maintenance dose between 8-24 mg/day over 1 to 3 days. Doses will be directly observed and occur daily. After a minimum of 2 weeks, dosing may be changed to 3 or 4 times per week, as determined clinically appropriate by the HIV clinic study physician. Dosing will remain flexible to a maximum dose of 24mg for daily dosing and 32mg for every other day dosing, as deemed clinically appropriate by the study physician.	Referral to methadone maintenance therapy for treatment of opioid dependence. Methadone Maintenance Therapy: Subjects randomized to methadone maintenance therapy (MMT) referral will meet with an HIV clinic case manager who will facilitate referral to MMT. Methadone dosing will be managed by MMT staff, who dispense methadone according to Ministry of Health guidelines for MMT.
Measure Participants	141	140
Viral suppression at baseline	97 68.8%	92 65.7%
Viral suppression at 12 months	74 52.5%	99 70.7%

2. Primary Outcome

Title	Participants With Heroin Use (Urine Drug Screen)
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Buprenorphine/Naloxone	Methadone Maintenance Therapy
Arm/Group Description	Office based treatment of opioid dependence with buprenorphine/naloxone Buprenorphine/naloxone: Buprenorphine/naloxone induction begins with a 2-4mg test dose followed by additional doses on the day of induction to relieve withdrawal symptoms, and then titrated to a maintenance dose between 8-24 mg/day over 1 to 3 days. Doses will be directly observed and occur daily. After a minimum of 2 weeks, dosing may be changed to 3 or 4 times per week, as determined clinically appropriate by the HIV clinic study physician. Dosing will remain flexible to a maximum dose of 24mg for daily dosing and 32mg for every other day dosing, as deemed clinically appropriate by the study physician.	Referral to methadone maintenance therapy for treatment of opioid dependence. Methadone Maintenance Therapy: Subjects randomized to methadone maintenance therapy (MMT) referral will meet with an HIV clinic case manager who will facilitate referral to MMT. Methadone dosing will be managed by MMT staff, who dispense methadone according to Ministry of Health guidelines for MMT.
Measure Participants	98	110
Count of Participants [Participants]	66 46.8%	72 51.4%

3. Primary Outcome

Title	Participants With Heroin Use (Self-report)
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Buprenorphine/Naloxone	Methadone Maintenance Therapy
Arm/Group Description	Office based treatment of opioid dependence with buprenorphine/naloxone Buprenorphine/naloxone: Buprenorphine/naloxone induction begins with a 2-4mg test dose followed by additional doses on the day of induction to relieve withdrawal symptoms, and then titrated to a maintenance dose between 8-24 mg/day over 1 to 3 days. Doses will be directly observed and occur daily. After a minimum of 2 weeks, dosing may be changed to 3 or 4 times per week, as determined clinically appropriate by the HIV clinic study physician. Dosing will remain flexible to a maximum dose of 24mg for daily dosing and 32mg for every other day dosing, as deemed clinically appropriate by the study physician.	Referral to methadone maintenance therapy for treatment of opioid dependence. Methadone Maintenance Therapy: Subjects randomized to methadone maintenance therapy (MMT) referral will meet with an HIV clinic case manager who will facilitate referral to MMT. Methadone dosing will be managed by MMT staff, who dispense methadone according to Ministry of Health guidelines for MMT.
Measure Participants	107	115
Count of Participants [Participants]	64 45.4%	67 47.9%

4. Secondary Outcome

Title	Number of Participants in Receipt of Antiretroviral Therapy (ART)
Description	Initiation of and retention on treatment with antiretroviral medications.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Buprenorphine/Naloxone	Methadone Maintenance Therapy
Arm/Group Description	Office based treatment of opioid dependence with buprenorphine/naloxone Buprenorphine/naloxone: Buprenorphine/naloxone induction begins with a 2-4mg test dose followed by additional doses on the day of induction to relieve withdrawal symptoms, and then titrated to a maintenance dose between 8-24 mg/day over 1 to 3 days. Doses will be directly observed and occur daily. After a minimum of 2 weeks, dosing may be changed to 3 or 4 times per week, as determined clinically appropriate by the HIV clinic study physician. Dosing will remain flexible to a maximum dose of 24mg for daily dosing and 32mg for every other day dosing, as deemed clinically appropriate by the study physician.	Referral to methadone maintenance therapy for treatment of opioid dependence. Methadone Maintenance Therapy: Subjects randomized to methadone maintenance therapy (MMT) referral will meet with an HIV clinic case manager who will facilitate referral to MMT. Methadone dosing will be managed by MMT staff, who dispense methadone according to Ministry of Health guidelines for MMT.
Measure Participants	128	131
Count of Participants [Participants]	108 76.6%	116 82.9%

5. Secondary Outcome

Title	Number of Participants in Retention in HIV Care
Description	HIV clinic visit in past 3 months
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Buprenorphine/Naloxone	Methadone Maintenance Therapy
Arm/Group Description	Office based treatment of opioid dependence with buprenorphine/naloxone Buprenorphine/naloxone: Buprenorphine/naloxone induction begins with a 2-4mg test dose followed by additional doses on the day of induction to relieve withdrawal symptoms, and then titrated to a maintenance dose between 8-24 mg/day over 1 to 3 days. Doses will be directly observed and occur daily. After a minimum of 2 weeks, dosing may be changed to 3 or 4 times per week, as determined clinically appropriate by the HIV clinic study physician. Dosing will remain flexible to a maximum dose of 24mg for daily dosing and 32mg for every other day dosing, as deemed clinically appropriate by the study physician.	Referral to methadone maintenance therapy for treatment of opioid dependence. Methadone Maintenance Therapy: Subjects randomized to methadone maintenance therapy (MMT) referral will meet with an HIV clinic case manager who will facilitate referral to MMT. Methadone dosing will be managed by MMT staff, who dispense methadone according to Ministry of Health guidelines for MMT.
Measure Participants	141	140
Count of Participants [Participants]	111 78.7%	118 84.3%

Adverse Events

Time Frame	4 years
Arm/Group Title	Buprenorphine/Naloxone		Methadone Maintenance Therapy
Arm/Group Description	Office based treatment of opioid dependence with buprenorphine/naloxone Buprenorphine/naloxone: Buprenorphine/naloxone induction begins with a 2-4mg test dose followed by additional doses on the day of induction to relieve withdrawal symptoms, and then titrated to a maintenance dose between 8-24 mg/day over 1 to 3 days. Doses will be directly observed and occur daily. After a minimum of 2 weeks, dosing may be changed to 3 or 4 times per week, as determined clinically appropriate by the HIV clinic study physician. Dosing will remain flexible to a maximum dose of 24mg for daily dosing and 32mg for every other day dosing, as deemed clinically appropriate by the study physician.		Referral to methadone maintenance therapy for treatment of opioid dependence. Methadone Maintenance Therapy: Subjects randomized to methadone maintenance therapy (MMT) referral will meet with an HIV clinic case manager who will facilitate referral to MMT. Methadone dosing will be managed by MMT staff, who dispense methadone according to Ministry of Health guidelines for MMT.
All Cause Mortality
	Buprenorphine/Naloxone		Methadone Maintenance Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/141 (5%)		3/140 (2.1%)
Serious Adverse Events
	Buprenorphine/Naloxone		Methadone Maintenance Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/141 (7.1%)		4/140 (2.9%)
General disorders
	1/141 (0.7%)	1	1/140 (0.7%)	1
Malaise	1/141 (0.7%)	1	0/140 (0%)	0
Immune system disorders
AIDS-related	3/141 (2.1%)	3	2/140 (1.4%)	2
Injury, poisoning and procedural complications
Accident, trauma, or external factor	6/141 (4.3%)	7	1/140 (0.7%)	1
Psychiatric disorders
Psychiatric	1/141 (0.7%)	1	0/140 (0%)	0
Suicide attempt	1/141 (0.7%)	1	0/140 (0%)	0
Renal and urinary disorders
Nephrogenic	1/141 (0.7%)	1	0/140 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory	1/141 (0.7%)	1	0/140 (0%)	0
Other (Not Including Serious) Adverse Events
	Buprenorphine/Naloxone		Methadone Maintenance Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/141 (16.3%)		3/140 (2.1%)
Cardiac disorders
Cardiac	1/141 (0.7%)	1	0/140 (0%)	0
Gastrointestinal disorders
Gastrointestinal	4/141 (2.8%)	4	0/140 (0%)	0
General disorders
Abnormal lab result	1/141 (0.7%)	1	0/140 (0%)	0
Headache	2/141 (1.4%)	2	0/140 (0%)	0
Malaise	1/141 (0.7%)	1	0/140 (0%)	0
Immune system disorders
Allergic reaction (non-study medication)	1/141 (0.7%)	1	0/140 (0%)	0
Infections and infestations
Suspected infection	5/141 (3.5%)	5	0/140 (0%)	0
Injury, poisoning and procedural complications
Unintentional injury	12/141 (8.5%)	12	2/140 (1.4%)	2
Nervous system disorders
Neuropathy	1/141 (0.7%)	1	1/140 (0.7%)	1
Vascular disorders
Vascular	1/141 (0.7%)	1	0/140 (0%)	0

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.