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CompletedNCT03290391LINC-IIUpdated Apr 18, 2023Results posted

Linking Infectious and Narcology Care-Part II

A Phase 4 interventional study of Rapid ART initiation and Pharmacotherapy for opioid use disorder in HIV Infection and Drug Use, sponsored by Boston Medical Center. Completed at 2 sites in Russian Federation. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-04-18.

Sponsored by Boston Medical Center · Phase 4, Interventional, and Health services research

Phase
Phase 4
Study type
Interventional
Enrollment
225
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This study, "Linking Infectious and Narcology Care - Part II (LINC-II)," will implement and evaluate a multi-faceted intervention (LINC-II), via a two-armed randomized controlled trial among 240 HIV-infected PWID in St. Petersburg. LINC-II, comprised of pharmacological therapy (i.e., rapid access to ART and receipt of naltrexone for opioid use disorder) and 12 months of strengths-based case management, will assess HIV outcomes (e.g., HIV viral load suppression), impact on care systems and cost-effectiveness of the intervention.

Read the detailed description

Russia and Eastern Europe continue to have one of the fastest growing HIV epidemics in the world, with highest transmission risks among people who inject drugs (PWID) and their sexual partners. While routine HIV testing within addiction treatment systems in Russia (i.e., narcology hospitals) is the norm, links between the narcology and HIV care systems are limited and ineffective. In St. Petersburg 50-60% of PWID are HIV-infected, yet among this population less than 10% are on antiretroviral therapy (ART). For Russia to make progress toward the UNAIDS 90-90-90 targets (i.e., 90% aware of HIV diagnosis, 90% of those diagnosed on ART and 90% of those on ART with suppressed HIV viral load [HVL]), a bold new strategy is required. The objective of this study, "Linking Infectious and Narcology Care - Part II (LINC-II)," is to implement and evaluate, via a two-armed randomized controlled trial among 240 HIV-infected PWID, a multi-faceted intervention combining pharmacological therapy (i.e., rapid access to ART and receipt of naltrexone for opioid use disorder) and 12 months of strengths-based case management.

The central hypothesis is that LINC-II will lead to marked progress toward the achievement of the 90-90-90 HIV cascade of care targets among HIV-infected PWID, relative to current standard of care, and that LINC-II will facilitate health system coordination of narcology and HIV care. LINC-II aims to: 1) evaluate the effectiveness of LINC-II on undetectable HVL at 12 months (primary outcome), initiation of ART within 28 days of randomization, change in CD4 count from baseline to 12 months, retention in HIV care (i.e., ≥ 1 visit to medical care in 2 consecutive 6 month periods), and undetectable HVL at 6 months; 2) evaluate the impact of LINC-II on coordinated care across the narcology and HIV health care systems, using mixed methods data from health care providers, administrators, and patients; and 3) evaluate the cost-effectiveness of the intervention to inform policy makers on scaling up the LINC-II approach both within Russia and other countries with HIV epidemics driven by injection drug use.

02

Conditions studied

  • HIV Infection
  • Drug Use

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Keywords

  • Russia
  • Substance use
  • Peer case managers
  • ART
  • HIV
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 18 years or older
  • HIV infected
  • Hospitalized at narcology hospital
  • History of injection drug use
  • Current diagnosis of opioid use disorder
  • Provision of information for 2 contacts to assist with follow-up
  • Address within 100 kilometers of St. Petersburg
  • Possession of a telephone (home or cell)
  • Able and willing to comply with all study protocols and procedures

Exclusion criteria

Exclusion Criteria:

  • Not fluent in Russian
  • Cognitive impairment
  • Pregnancy, planning to become pregnant, or breastfeeding
  • ART use in past 30 days prior to hospitalization
  • Known hypersensitivity to naltrexone
  • Acute severe psychiatric illness (i.e. ,answered yes to any of the following: past three month active hallucinations; mental health symptoms prompting a visit to the ED or hospital; mental health medication changes due to worsening symptoms; presence of suicidal ideations)
  • Known history of liver failure
  • ALT or AST >5 times the upper limit of normal
  • Known severe thrombocytopenia (\<50k)
  • Known coagulation disorder/taking anticoagulation medications
  • Body habitus that precludes intramuscular injection
  • Known hypersensitivity to naloxone
  • Known history of Raynaud's disease
  • Known history of Itsenko-Cushing syndrome
  • Known history of generalized mycoses
  • Known history of glaucoma
  • Known history of osteoporosis.
  • Planned surgeries in the next 12 months
04

Study design

Phase
Phase 4
Primary purpose
Health services research
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
225 participants (actual)

Study arms

  • Experimental
    LINC-II

    LINC-II is a multi-faceted intervention combining pharmacological therapy (i.e., ART and naltrexone for opioid use disorder) and 12 months of strengths-based case management delivered to coordinate care across the narcology and HIV health care systems.

    Other: Rapid ART initiation · Drug: Pharmacotherapy for opioid use disorder · Behavioral: Strengths-based HIV case management

  • No intervention
    Standard of Care

    Participants randomized to the control group will receive the narcology hospital's standard of care, which is detoxification with or without stabilization. Prior to discharge, those identified as HIV-infected are given contact details for an HIV clinic, not an appointment. Upon discharge, patients are encouraged to receive outpatient narcology treatment, monthly, for 1 year. For this study, with regard to linkage to HIV medical care, patients will be given printed information about where to obtain HIV medical care and a resource card containing harm reduction information.

Interventions

  • OtherRapid ART initiation

    The infectionist will streamline the approval with the ultimate goal of starting participants on ART while they are still hospitalized at the City Addiction Hospital.

  • DrugPharmacotherapy for opioid use disorder

    Thirteen months of naltrexone treatment for opioid use disorder (injection at baseline, followed by 4 implants).

    Also known as: Naltrexone

  • BehavioralStrengths-based HIV case management

    Strengths-based case management: 10 sessions over 12 months in which a trained case manager (CM) meets individually with patients to motivate them to engage in HIV medical care by supporting the recognition of their own strengths to make positive changes in their lives and ultimately improve their HIV outcomes.

05

What researchers measure

Primary outcomes

  1. Undetectable HIV Viral Load at 12 Months

    Number of participants with undetectable HIV viral load at 12 months, assessed by HIV viral load lab test (\<40 copies per milliliter)

    Time frame: 12 months post randomization

Secondary outcomes

  1. Initiation of Antiretroviral Therapy (ART)

    Number of participants who initiated ART within 28 days of randomization. Data will be extracted from medical record.

    Time frame: Within 28 days of randomization

  2. Change in Mean CD4 Count From Baseline to 12 Months

    The change in the mean CD4 count (CD4 cells per cubic millimeter) will be calculated from the baseline and 12 months lab results

    Time frame: Change from baseline to 12 months

  3. Retention in HIV Care

    Number of participants who had at least 1 visit to HIV medical care in 2 consecutive 6 month periods. Data will be extracted from medical record.

    Time frame: 12 months

  4. Undetectable HIV Viral Load at 6 Months

    Number of participants with undetectable HIV viral load at 6 months, assessed by HIV viral load lab test (\<40 copies per milliliter).

    Time frame: 6 months

06

Results

Posted Apr 18, 2023

Participant flow

Allocation
Participant flow — Allocation
MilestoneLINC-IIStandard of Care
Started111114
Completed111114
Not completed00
Completed 6 Month Assessment
Participant flow — Completed 6 Month Assessment
MilestoneLINC-IIStandard of Care
Started111114
Completed7985
Not completed3229
Completed 12 Month Assessment
Participant flow — Completed 12 Month Assessment
MilestoneLINC-IIStandard of Care
Started111114
Completed8283
Not completed2931

Outcome measures

PrimaryUndetectable HIV Viral Load at 12 Months

Number of participants with undetectable HIV viral load at 12 months, assessed by HIV viral load lab test (\<40 copies per milliliter)

Time frame:
12 months post randomization
Reported as:
Number · percentage of participants
Undetectable HIV Viral Load at 12 Months
percentage of participantsLINC-IIStandard of Care
Undetectable HIV Viral Load at 12 Months46.922.7
SecondaryInitiation of Antiretroviral Therapy (ART)

Number of participants who initiated ART within 28 days of randomization. Data will be extracted from medical record.

Time frame:
Within 28 days of randomization
Reported as:
Number · percentage of participants
Initiation of Antiretroviral Therapy (ART)
percentage of participantsLINC-IIStandard of Care
Initiation of Antiretroviral Therapy (ART)73.911.4
SecondaryChange in Mean CD4 Count From Baseline to 12 Months

The change in the mean CD4 count (CD4 cells per cubic millimeter) will be calculated from the baseline and 12 months lab results

Time frame:
Change from baseline to 12 months
Reported as:
Mean · cells per cubic millimeter
Change in Mean CD4 Count From Baseline to 12 Months
cells per cubic millimeterLINC-IIStandard of Care
Change in Mean CD4 Count From Baseline to 12 Months56 ± 171-8 ± 193
SecondaryRetention in HIV Care

Number of participants who had at least 1 visit to HIV medical care in 2 consecutive 6 month periods. Data will be extracted from medical record.

Time frame:
12 months
Reported as:
Number · percentage of participants
Retention in HIV Care
percentage of participantsLINC-IIStandard of Care
Retention in HIV Care51.435.1
SecondaryUndetectable HIV Viral Load at 6 Months

Number of participants with undetectable HIV viral load at 6 months, assessed by HIV viral load lab test (\<40 copies per milliliter).

Time frame:
6 months
Reported as:
Number · percentage of participants
Undetectable HIV Viral Load at 6 Months
percentage of participantsLINC-IIStandard of Care
Undetectable HIV Viral Load at 6 Months35.412.9

Adverse events

Collected over Adverse event data were collected over the course of the 12-month study period.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
LINC-II4/111 (3.6%)9/111 (8.1%)13/111 (11.7%)
Standard of Care10/114 (8.8%)13/114 (11.4%)3/114 (2.6%)
Most frequent serious events
Most frequent serious events
EventLINC-IIStandard of Care
PneumoniaInfections and infestations4/1111/114
Death due to overdoseSocial circumstances3/1112/114
Death due to heart failureCardiac disorders1/1113/114
Death due to COVIDInfections and infestations0/1112/114
TuberculosisRespiratory, thoracic and mediastinal disorders1/1111/114
Acute bronchitisRespiratory, thoracic and mediastinal disorders0/1111/114
Death due to suicideSocial circumstances0/1111/114
Death due to sepsisInfections and infestations0/1111/114
Death due to acute alcohol intoxicationSocial circumstances0/1111/114
Most frequent other events
Showing 10 of 13
Most frequent other events
EventLINC-IIStandard of Care
PneumoniaInfections and infestations4/1111/114
Elevated ASTInvestigations4/1110/114
Back painMusculoskeletal and connective tissue disorders1/1110/114
Muscle painMusculoskeletal and connective tissue disorders1/1110/114
InsomniaPsychiatric disorders1/1110/114
General weaknessGeneral disorders1/1110/114
HyperbilirubinemiaHepatobiliary disorders1/1110/114
Elevated ALTInvestigations1/1110/114
Wound infectionSurgical and medical procedures1/1110/114
Skin irritationSkin and subcutaneous tissue disorders1/1110/114

Baseline characteristics

Age, Continuous
Age, Continuous(years)LINC-IIStandard of CareTotal
Mean37 ± 537 ± 537 ± 5
Sex: Female, Male
Sex: Female, Male(Participants)LINC-IIStandard of CareTotal
Female474289
Male6472136
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)LINC-IIStandard of CareTotal
Hispanic or Latino000
Not Hispanic or Latino111114225
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)LINC-IIStandard of CareTotal
American Indian or Alaska Native000
Asian011
Native Hawaiian or Other Pacific Islander000
Black or African American000
White110113223
More than one race000
Unknown or Not Reported101
Region of Enrollment
Region of Enrollment(Participants)LINC-IIStandard of CareTotal
Russia111114225
07

Study locations

2 sites
  • First St. Petersburg Pavlov State Medical University
    St. Petersburg, 197022, Russian Federation
  • City Addiction Hospital
    St. Petersburg, Russian Federation
08

References and documents

Publications

  • Bovell-Ammon BJ, Kimmel SD, Cheng DM, Truong V, Michals A, Vetrova M, Hook K, Idrisov B, Blokhina E, Krupitsky E, Samet JH, Lunze K. Incarceration history, antiretroviral therapy, and stigma: A cross-sectional study of people with HIV who inject drugs in St. Petersburg, Russia. Int J Drug Policy. 2023 Jan;111:103907. doi: 10.1016/j.drugpo.2022.103907. Epub 2022 Nov 17. PubMed 36402082 ↗
  • Gnatienko N, Lioznov D, Raj A, Blokhina E, Rosen S, Cheng DM, Lunze K, Bendiks S, Truong V, Bushara N, Toussova O, Quinn E, Krupitsky E, Samet JH. Design of a randomized controlled trial to Link Infectious and Narcology Care (LINC-II) in St. Petersburg, Russia. Addict Sci Clin Pract. 2020 Jan 13;15(1):1. doi: 10.1186/s13722-020-0179-8. PubMed 31931884 ↗

Study documents

  • Protocol and statistical analysis plan · Jul 22, 2021
  • Informed consent form · Feb 24, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03290391
Lead sponsor
Boston Medical Center
Collaborators
National Institute on Drug Abuse (NIDA)
Responsible party
Sponsor
First posted
Sep 21, 2017
Start date
Sep 19, 2018
Primary completion
Apr 6, 2022
Completion
Apr 6, 2022
Results posted
Apr 18, 2023
Last update
Apr 18, 2023

Study contacts

Jeffrey Samet, MD MA MPH
principal investigator · Boston University

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Mar 2023. You cannot join it, but the record below documents what was studied.

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