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Start TB Patients on ART and Retain on Treatment (START Study)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Columbia University
Sponsor:
Collaborator:
United States Agency for International Development (USAID)
Information provided by (Responsible Party):
Andrea Howard, Columbia University
ClinicalTrials.gov Identifier:
NCT01872390
First received: May 31, 2013
Last updated: September 15, 2014
Last verified: September 2014
  Purpose

Lesotho, a small, landlocked country completely surrounded by South Africa, is among the world's poorest nations with one of the world's most severe epidemics of HIV and tuberculosis (TB). There is strong evidence that TB patients who are also infected with HIV have better survival rates if they begin antiretroviral therapy (ART) soon after starting TB treatment; however, there are many patients who do not initiate ART within the recommended timeframe, and who do not remain in care.

The purpose of the START Study is to identify an effective, cost-effective, acceptable intervention that addresses programmatic, structural and psychosocial barriers to ART initiation and retention during TB treatment, with the ultimate goal of improving health outcomes among HIV-infected TB patients in Lesotho. The study is a two-arm cluster randomized trial, randomized at the TB/HIV clinic level, which includes twelve TB/HIV clinics in Berea district. Clinics are randomized to deliver the combination intervention package (CIP) or standard of care (SOC), with stratification by facility type. The experimental intervention will be delivered to all HIV-infected TB patients in TB/HIV clinics randomly assigned to CIP. In TB/HIV clinics assigned to SOC, usual care procedures for ART initiation and retention will be delivered.

Study hypotheses focus on the effectiveness of the CIP on HIV- and TB-related outcomes.

Compared to HIV-infected TB patients attending SOC clinics, HIV-infected TB patients at CIP clinics will have superior HIV- and TB-related outcomes, including:

  • Greater ART initiation during TB treatment
  • Shorter time to ART initiation
  • Greater retention in ART care
  • Higher adherence to ART
  • Greater change in CD4+ count
  • Greater TB treatment success (completion and cure)
  • Greater sputum smear conversion
  • Higher adherence to TB treatment

Additionally, CIP delivery will have an incremental cost-effectiveness ratio more favorable than alternative resource uses.


Condition Intervention
Tuberculosis
HIV
Other: Combination Intervention Package
Other: Standard of Care

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Start TB Patients on ART and Retain on Treatment: Combination Intervention Package to Enhance Antiretroviral Therapy Uptake and Retention During TB Treatment in Lesotho

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • ART initiation [ Time Frame: Up to 9 months ] [ Designated as safety issue: No ]
    Percentage of TB/HIV patients newly registered during period of observation who initiate ART during TB treatment, based on review of clinic registers.

  • ART retention [ Time Frame: Up to 6 months after TB treatment initiation ] [ Designated as safety issue: No ]
    Percentage of participants who attended 6 month clinic visit (within 1 month window) and reported ART use. Deaths and transfers will be considered not retained.

  • TB treatment success [ Time Frame: Up to 9 months ] [ Designated as safety issue: No ]
    Cure and treatment completion at end of TB treatment as defined by WHO, based on review of TB register and treatment cards.


Secondary Outcome Measures:
  • Time to ART initiation [ Time Frame: Up to 9 months ] [ Designated as safety issue: No ]
    Days from TB treatment initiation to date of ART initiation.

  • ART adherence [ Time Frame: Up to 9 months ] [ Designated as safety issue: No ]
    Percentage of total prescribed doses ingested, averaged across medicines for each month of treatment, from the unannounced pill counts.

  • Change in CD4+ count [ Time Frame: Up to 6 months after initial CD4 count ] [ Designated as safety issue: No ]
    Change in CD4 count over 6 months (from initiation of TB treatment to 6 months later). Routine clinical CD4 test results will be used by study staff and no additional blood draw will be required.

  • Sputum smear conversions [ Time Frame: Up to 8 weeks from initiation of TB treatment ] [ Designated as safety issue: No ]
    Percentage of smear positive pulmonary TB cases that converted to smear negative after eight weeks of treatment.

  • TB treatment adherence [ Time Frame: Up to 9 months ] [ Designated as safety issue: No ]
    Percentage of total prescribed doses ingested, from unannounced pill counts

  • Cost-effectiveness (incremental cost per health adjusted life-year gained) of the CIP program [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    incremental change in costs divided by incremental change in effects


Estimated Enrollment: 444
Study Start Date: April 2013
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combination Intervention Package (CIP)
  1. nurse training and mentorship in TB/HIV cotreatment using clinical algorithm
  2. reimbursement of transportation costs to monthly clinic visits for patients and treatment supporters
  3. health education using a TB/HIV treatment literacy curriculum for patients and treatment supporters
  4. real-time adherence support using short message service (SMS) text messaging and trained village health workers.
Other: Combination Intervention Package
CIP will contain programmatic, structural and psychosocial components including: 1) nurse training and mentorship in TB/HIV co-treatment using a clinical algorithm; 2) reimbursement of transportation costs to monthly clinic visits for patients and treatment supporters; 3) health education using a TB and HIV treatment literacy curriculum for patients and treatment supporters; and 4) real-time adherence support using SMS text messaging and trained village health workers.
Standard of Care
At SOC clinics, usual procedures for management of HIV-infected TB patients will be followed. At health centers, TB and HIV services are fully integrated in a one-stop model, while at hospitals, ART is provided in the TB clinic for TB/HIV coinfected patients. Nurses, lay counselors, and VHW provide TB/HIV services. Lay counselors offer HIV counseling and testing to all TB patients. As per national guidelines, HIV-infected TB patients are to be started on ART two to four weeks after initiating TB treatment, regardless of CD4+ count. Directly observed therapy is usually provided in the community by a treatment supporter, who is usually a family member. TB/HIV patients return to the health facility monthly for a 30-day supply of medications and monitoring of side effects and adherence.
Other: Standard of Care
At SOC clinics, usual procedures for management of HIV-infected TB patients will be followed. At health centers, TB and HIV services are fully integrated in a one-stop model, while at hospitals, ART is provided in the TB clinic for TB/HIV coinfected patients. Nurses, lay counselors, and VHW provide TB/HIV services. Lay counselors offer HIV counseling and testing to all TB patients. As per national guidelines, HIV-infected TB patients are to be started on ART two to four weeks after initiating TB treatment, regardless of CD4+ count. Directly observed therapy is usually provided in the community by a treatment supporter, who is usually a family member. TB/HIV patients return to the health facility monthly for a 30-day supply of medications and monitoring of side effects and adherence.

  Hide Detailed Description

Detailed Description:

The study intervention, combination intervention package (CIP), will contain multiple components, including: 1) nurse training and mentorship in TB/HIV co-treatment using a clinical algorithm; 2) reimbursement of transportation costs to monthly clinic visits for patients and their treatment supporters; 3) health education using a TB and HIV treatment literacy curriculum for patients and treatment supporters; and 4) real-time adherence support using short message service (SMS) text messaging and trained village health workers (VHW). Nurses and VHW will be trained to deliver the intervention to all TB/HIV patients in CIP clinics. Participants in this study will complete their monthly clinic visits with clinic staff, per routine care.

Data will be collected from all HIV-infected TB patients newly enrolled in care; from a subset of patients enrolled into a measurement cohort (MC); from program characteristics surveys conducted at the study sites; and from key informant groups. Routine clinic data from all HIV-infected TB patients newly registered at the 12 participating clinics during the period of observation will be used to measure the following outcomes: ART initiation, time to ART initiation, TB treatment success, and sputum smear conversion. These data will be collected by Research Assistants by abstracting the following information from the clinic TB and ART registers during the period of observation on all newly registered TB/HIV patients: date of TB treatment initiation; ART initiation (yes/no); date of ART initiation (if applicable); TB treatment outcomes (completion, cure, failure, death, default); TB type; and all sputum smear results.

A measurement cohort (MC) of 384 HIV-infected TB patients initiating ART will be recruited from the 12 clinics (n=192 per study arm). MC participants will be assessed at baseline (enrollment) and monthly intervals for six to nine months, depending on the duration of TB treatment. Outcomes to be measured among MC participants include: retention in ART care, adherence to ART, change in CD4+ count, adherence to TB treatment, and side effects/adverse events. MC participants at both SOC and CIP sites will receive the same assessments. Research Assistants will administer assessments on the day of regularly scheduled clinic visits, including a Baseline interview administered on the day of enrollment (which coincides with the day a participant initiates ART), Monthly Follow-Up interviews completed throughout TB treatment on a monthly basis, and an End of Treatment interview that is completed on the day the participant ends TB treatment. Participants who miss a study visit will be contacted by study staff and administered the questionnaire over the phone within a 1-week window period. Research Assistants will also call the MC participants between clinic visits to conduct unannounced pill counts to assess medication adherence.

Cost drivers associated with CIP, including program, medical, and patient costs, will be collected.

Research Assistants (RAs) will conduct an assessment of programmatic activities at each TB/HIV clinic prior to study implementation and on a monthly basis thereafter. Clinics in both conditions will receive the same assessments. The RA will administer a brief semi-structured Program Characteristics survey to the nurse in charge, who will be most familiar with the day-to-day operations of the TB/HIV clinic. The survey will assess nurse training and mentorship in TB/HIV cotreatment, availability and use of a TB/HIV clinical algorithm, TB/HIV adherence training for VHW, TB/HIV health education for patients and treatment supporters, availability and use of a TB/HIV treatment literacy curriculum, reimbursement for transportation costs for patients and treatment supporters, provision of air-time vouchers for TB/HIV patients on ART, use of SMS messaging for adherence support and appointment reminders, and provision of community-based adherence and side effect monitoring by VHW. These data will be used to assess fidelity with the intervention at CIP sites, as well as to measure any potential contamination at SOC sites. Additional cost information will be analyzed from the expenditures associated with parts of the CIP, as paid for by the study budget.

Three key informant (KI) groups will be recruited from CIP clinics: ART early-initiators (n=30), ART non/late-initiators (n=30), and health care workers (including nurses and VHW) (n=30). KI interviews will assess: acceptability and preferences of intervention components, as well as reasons for ART non/late-initiation. Senior Research Assistants will use Key Informant interview (KII) guides developed by the investigators to conduct semi-structured interviews with KI recruited from CIP sites. Each interview will be digitally recorded, transcribed verbatim, and translated to English. Acceptability, preferences and utilization of intervention components will be explored among CIP participants in the measurement cohort at the end of TB treatment. Reasons for non/late-initiation of ART will be explored among TB/HIV patients who have completed TB treatment and have never initiated ART or who initiated ART two months after TB treatment initiation at a CIP site. Healthcare worker experiences delivering the intervention, perceived barriers and facilitators, perceptions about acceptability and ease of uptake and delivery of the various components of the intervention will be explored among nurses and VHW at CIP sites.

All clinical care, including implementation of the combination intervention package at sites randomized to CIP, will be performed by Lesotho Ministry of Health clinic staff (nurses and VHW). All study procedures, including participant interviews, pill counts, medical record abstraction, and program characteristics surveys will be performed by study staff (Research Assistants). Following routine clinic visits, clinic staff will refer potentially eligible patients to study staff, who will screen for eligibility, obtain informed consent, and enroll consenting eligible patients into the measurement cohort.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Measurement Cohort Inclusion Criteria:

  1. HIV-infected;
  2. initiated TB treatment at study site after study implementation;
  3. initiated ART within 2 months of TB treatment initiation;
  4. aged 18 or older;
  5. English- or Sesotho-speaking;
  6. capable of and willing to provide informed consent within 3 working days of ART initiation

Measurement Cohort Exclusion Criteria:

  1. children under age of 18
  2. patients diagnosed with multi-drug resistant (MDR) TB

Key Informants ART Early-Initiators Inclusion Criterion:

  1. Measurement cohort participant
  2. Initiated ART at minimum 2 weeks prior to completion of Key Informant Interview

Key Informants ART Non/Late-Initiators Inclusion Criteria:

  1. HIV-infected;
  2. recently completed TB treatment at CIP clinic (if non-initiators), or on TB treatment >= 2 months (if late-initiators);
  3. ART naïve or ART initiated >= 2 months after TB treatment initiation;
  4. aged 18 or older;
  5. English- or Sesotho-speaking;
  6. capable of and willing to provide informed consent.

Key Informants ART Non/Late-Initiators Exclusion Criteria:

  1. children under age of 18
  2. patients diagnosed with multi-drug resistant (MDR) TB

Key Informants Healthcare Workers Inclusion Criteria:

  1. nurse or VHW working in a CIP clinic or VHW working in the community and affiliated with CIP clinic;
  2. aged 18 or older;
  3. English or Sesotho‐speaking;
  4. capable of and willing to provide informed consent.

Key Informants Healthcare Workers Exclusion Criteria

  1. Children under age 18
  2. Nurse or VHW working in or affiliated with a SOC clinic
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01872390

Contacts
Contact: Mary Vachon 212-305-1348 mv326@columbia.edu

Locations
Lesotho
Khubetsoana Health Center Recruiting
Berea, Berea District, Lesotho
Contact: Mashale Shale    +26622326599    shalem@icap.org.ls   
Sub-Investigator: Koen Frederix, MD         
Good Shepherd Health Center Recruiting
Berea, Berea District, Lesotho
Contact: Mashale Shale    +26622326599    shalem@icap.org.ls   
Sub-Investigator: Koen Frederix, MD         
Holy Family Health Center Recruiting
Berea, Berea District, Lesotho
Contact: Mashale Shale    +26622326599    shalem@icap.org.ls   
Sub-Investigator: Koen Frederix, MD         
St. Theresa Health Center Recruiting
Berea, Berea District, Lesotho
Contact: Mashale Shale    +26622326599    shalem@icap.org.ls   
Sub-Investigator: Koen Frederix, MD         
Koali Health Center Recruiting
Berea, Berea District, Lesotho
Contact: Mashale Shale    +26622326599    shalem@icap.org.ls   
Sub-Investigator: Koen Frederix, MD         
Kolojane Health Center Recruiting
Berea, Berea District, Lesotho
Contact: Mashale Shale    +26622326599    shalem@icap.org.ls   
Sub-Investigator: Koen Frederix, MD         
Maluti Hospital Recruiting
Berea, Berea District, Lesotho
Contact: Mashale Shale    +26622326599    shalem@icap.org.ls   
Sub-Investigator: Koen Frederix, MD         
Pilot Health Center Recruiting
Berea, Berea District, Lesotho
Contact: Mashale Shale    +26622326599    shalem@icap.org.ls   
Sub-Investigator: Koen Frederix, MD         
Sebedia Health Center Recruiting
Berea, Berea District, Lesotho
Contact: Mashele Shale    +26622326599    shalem@icap.org.ls   
Sub-Investigator: Koen Frederix, MD         
St Magdalena Health Center Recruiting
Berea, Berea District, Lesotho
Contact: Mashale Shale    +26622326599    shalem@icap.org.ls   
Sub-Investigator: Koen Frederix, MD         
St. David Health Center Recruiting
Berea, Berea District, Lesotho
Contact: Mashale Shale    +26622326599    shalem@icap.org.ls   
Sub-Investigator: Koen Frederix, MD         
Berea Hospital Recruiting
Berea, Berea District, Lesotho
Contact: Mashale Shale    +26622326599    shalem@icap.org.ls   
Sub-Investigator: Koen Frederix, MD         
Sponsors and Collaborators
Columbia University
United States Agency for International Development (USAID)
Investigators
Principal Investigator: Andrea A Howard, MD Columbia University
  More Information

No publications provided

Responsible Party: Andrea Howard, Associate Professor of Clinical Epidemiology (in ICAP), Columbia University
ClinicalTrials.gov Identifier: NCT01872390     History of Changes
Other Study ID Numbers: AAAK7103, AID-OAA-A-12-00022
Study First Received: May 31, 2013
Last Updated: September 15, 2014
Health Authority: United States: Institutional Review Board
Lesotho: Institutional Review Board

Keywords provided by Columbia University:
Lesotho
TB
tuberculosis
HIV
antiretroviral therapy
ART
adherence
combination intervention package
retention

Additional relevant MeSH terms:
Tuberculosis
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Mycobacterium Infections

ClinicalTrials.gov processed this record on November 25, 2014