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Sustainable East Africa Research in Community Health (SEARCH)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by University of California, San Francisco
Sponsor:
Collaborators:
Infectious Diseases Research Collaboration, Uganda
Makerere University
Kenya Medical Research Institute
Gilead Sciences
World Bank
National Institute of Allergy and Infectious Diseases (NIAID)
United States President's Emergency Plan for AIDS Relief
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01864603
First received: April 26, 2013
Last updated: September 30, 2016
Last verified: September 2016
  Purpose
The SEARCH study aims to test evidenced-based innovative community based interventions that lead to the elimination of HIV in rural communities in East Africa using a multi-disease approach. The first phase of the study will quantify the health, economic and educational impact of early HIV diagnosis using a streamlined and immediate ART (antiretroviral therapy). This first phase will be completed in July 2017. The second phase of the study, will quantify the health, economic and educational impact of targeted Pre-Exposure Prophylaxis (PrEP), targeted HIV testing and targeted care interventions in the context of universal treatment and streamlined care. This second phase will be completed in July 2020. The study intervention is designed to improve the entire continuum of care, to reduce structural barriers for all populations including those most "at risk".

Condition Intervention
HIV
Tuberculosis
Hypertension
Diabetes
Maternal Child Health
Cost Effectiveness
Other: Universal ART in a streamlined care model
Other: Annual Community Health Campaigns
Other: Targeted PrEP, Targeted testing, and Targeted care interventions
Other: Baseline community-based HIV and multi-disease testing

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Sustainable East Africa Research in Community Health

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Cumulative HIV incidence [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Cumulative 3 year HIV incidence in men and women ages ≥15 years after the start of Phase I intervention.

  • Cumulative HIV incidence [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Cumulative 3 year HIV incidence in men and women ages ≥15 years after the start of Phase II intervention (started after 3 years of Phase I).


Secondary Outcome Measures:
  • Time from diagnosis to AIDS [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To compare time from diagnosis to AIDS between the 2 study arms.

  • Incidence of AIDS-defining events between the study arms [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To compare incidence of AIDS-defining events between the study arms.

  • Total TB and incident TB cases associated with HIV [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    TTo compare proportion of total TB and incident TB cases associated with HIV between the study arms.

  • Overall mortality [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To compare mortality between the 2 study arms.

  • Maternal and child mortality [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To compare number of maternal and child deaths between the 2 study arms.

  • Mother to child HIV transmission [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To compare mother to child HIV transmission between the 2 study arms.

  • Population HIV RNA metrics [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To compare population HIV RNA metrics between the 2 study arms. HIV metrics include: % with HIV viral suppression; median population HIV RNA level; % HIV RNA by strata i.e. greater than 100,000 vs. <100,000 copies/ml

  • Association between population HIV RNA metrics and HIV incidence [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To determine the association between population HIV RNA metrics and HIV incidence. HIV metrics include: % with HIV viral suppression; median population HIV RNA level; % HIV RNA by strata i.e. greater than 100,000 vs. <100,000 copies/ml

  • Prevalence of transmitted HIV drug-resistance mutations [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To compare the prevalence (number of participants with) of transmitted HIV drug-resistance mutations and pharmacologic measures of ART between the study arms after 3 and 6 years of follow up.

  • Rates of linkage to and retention in care for HIV [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To compare rates of linkage to and retention in care for HIV between the study arms.

  • Time to ART-initiation [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To compare time to ART-initiation between the study arms.

  • Time to CD4 cell count recovery in Phase I of high CD4 count individuals (CD4>350) [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    Time to CD4 cell count recovery above 350 after enrollment

  • Rate of virologic suppression in Phase I of high CD4 count individuals (CD4>350) [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    Time to viral load measurements below detectable

  • Treatment-associated toxicities and grade 3 and 4 adverse events in Phase I of high CD4 count individuals (CD4>350) [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: Yes ]
    DAIDS toxicity table symptoms grade 3 or 4

  • Prevalence of HIV drug resistant mutations after 1 and 2 years of treatment in Phase I of high CD4 count individuals (CD4>350) [ Time Frame: 3 years follow up ] [ Designated as safety issue: No ]
    Number of patients with HIV drug resistant mutations measured after 1 and 2 years of treatment

  • Cumulative incidence of internally derived HIV infections [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To compare the 3 and 6 year cumulative incidence of internally derived HIV infections (infections genetically linked to a prior infection among members of the same community) between the study arms.

  • Evaluate attitudes of community, patients and providers on care delivery in control and intervention communities [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To evaluate attitudes of community, patients and providers on care delivery in control and intervention communities using qualitative focus group interviews

  • Evaluate implementation of other disease care cascades (hypertension, diabetes, women and children health services) [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    Uptake of testing, linkage to care and retention to care

  • Prevalence of complications of diabetes, hypertension and chronic kidney disease (CKD) and to understand the genetic susceptibility of diseases in the study populations. [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    Number of patients with of complications of diabetes, hypertension and chronic kidney disease (CKD) and to understand the genetic susceptibility of diseases in the study populations in Phase II.

  • Adherence to PrEP treatment [ Time Frame: 3 years follow up ] [ Designated as safety issue: No ]
    Number of patients who adherence to PrEP treatment

  • Change in attitudes towards PrEP [ Time Frame: 3 years follow up ] [ Designated as safety issue: No ]
    Qualitative focus group discussions on attitudes toward PrEP

  • Change in average levels of adults' on- and off-farm employment [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To compare the trends in average levels of adults' on- and off-farm employment between the 2 study arms.

  • Change in average levels of children's on- and off-farm employment [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To compare the trends in average levels of children's on- and off-farm employment (child labor) between the 2 study arms.

  • Change in average levels of children's time allocation to schooling and household activities [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To compare the trends in average levels of children's time allocation to schooling and household activities between the 2 study arms.

  • Change in average asset holdings [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To compare the trends in average asset holdings (durable good and livestock) between the 2 study arms.

  • Change in agricultural output and other economic production [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To compare the trends in agricultural output and other economic production, such as fishing, between the 2 study arms.

  • Change in average levels of cash and in-kind transfers [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To compare the trends in average levels of cash and in-kind transfers between the 2 study arms.

  • Total costs of programming [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To compare costs of programming (campaigns, ART) and PrEP (Phase II only) between the study arms: overall; per person identified, linked to care, and started on ART; and per ART-month, CD4 level recovered, and viral load suppressed.

  • Change in disease burden [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To compare disease burden (expressed in disability adjusted life years, DALYs) between the 2 study arms, during and modelled beyond the study period.

  • Savings from averted disease associated treatment costs [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To compare the savings from averted disease associated treatment costs between the 2 study arms.

  • Occurrence and consequences of false positive HIV diagnosis [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To compare the occurrence and consequences of false positive (new) HIV diagnosis

  • Cost-effectiveness of the intervention [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To calculate the incremental cost-effectiveness of the intervention, as net cost per DALY averted.

  • Evaluate streamlined care of HIV patients [ Time Frame: 3 and 6 years follow up ] [ Designated as safety issue: No ]
    To evaluate streamlined vs. non-streamlined care including time and motion studies for staff and clients (Phase I only).

  • Number of participants in targeted PrEP vs. country standard PrEP [ Time Frame: 3 years follow up ] [ Designated as safety issue: No ]
    Numbers of participants who accept targeted linkage for PrEP, retention of PrEP treatment, and suppression interventions including time in motion studies for staff and clients (Phase II only).


Estimated Enrollment: 340000
Study Start Date: April 2013
Estimated Study Completion Date: July 2020
Estimated Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1st: universal test and treat; 2nd: targeted PrEP and cascade

Intervention arm first phase: annual universal community-based HIV and multi-disease testing; ART for all HIV+ using streamlined care delivery

Intervention arm second phase: baseline universal community-based HIV and multi-disease testing; ART for all HIV+ using streamlined care delivery + targeted PrEP, targeted HIV testing, and targeted care interventions

Other: Universal ART in a streamlined care model
immediate ART start for all HIV+ in community with streamlined care
Other: Annual Community Health Campaigns
HIV and multi-disease testing for all community members
Other: Targeted PrEP, Targeted testing, and Targeted care interventions
Active Comparator: 1st: baseline community testing; 2nd: universal test & treat

Intervention arm first phase: baseline community-based HIV and multi-disease testing

Intervention arm second: baseline universal community-based HIV and multi-disease testing; ART for all HIV+ using streamlined care delivery

Other: Universal ART in a streamlined care model
immediate ART start for all HIV+ in community with streamlined care
Other: Baseline community-based HIV and multi-disease testing
HIV and multi-disease testing for all community members at baseline only

Detailed Description:
The SEARCH study aims to test evidenced-based innovative community based interventions that lead to the elimination of HIV in rural communities in East Africa using a multi-disease approach. The first phase of the study will quantify the health, economic and educational impact of early HIV diagnosis using a streamlined and immediate ART (antiretroviral therapy). This first phase will be completed in July 2017. The second phase of the study, will quantify the health, economic and educational impact of targeted Pre-Exposure Prophylaxis (PrEP), targeted HIV testing and targeted care interventions in the context of universal treatment and streamlined care. This second phase will be completed in July 2020. The study intervention is designed to improve the entire continuum of care, to reduce structural barriers for all populations including those most "at risk". Primary endpoint for the first and second phase is HIV incidence measured 3 years follow up.
  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Community Level Inclusion Criteria:

  • Non-adjacent geopolitical units in south-western and eastern Uganda and western Kenya.
  • Most recent census population between 9,000 and 11,000 individuals.
  • Served by an ART providing health center.
  • Community leader commitment for study participation and implementation.
  • Accessibility to health center via a maintained transportation route.
  • Community location with sufficient distance from other potential study communities to limit contamination of intervention or control conditions (buffer zone)

Individual Level Inclusion Criteria:

  • Residency of individual in community, defined as present in household for at least 6 months of the calendar year.

Community Level Exclusion Criteria:

  • Presence of ongoing community-based ART intervention strategies that provide treatment outside of the current in-country treatment guidelines.
  • An urban setting defined as a city with a population of 100,000 or more inhabitants.
  • Absence of a health center able to provide ART.
  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: NCT01864603

Contacts
Contact: Tamara Clark, MHS tclark@medsfgh.ucsf.edu

Locations
Kenya
Nyanza Province Kenya Recruiting
Nyanza Province, Kenya
Principal Investigator: Elizabeth Bukusi, MBChB, PhD         
Uganda
Eastern Uganda Recruiting
Mbale/Tororo region, Uganda
Principal Investigator: Moses Kamya, MBChB, PhD         
Southwestern Uganda Recruiting
Mbarara region, Uganda
Principal Investigator: Moses Kamya, MBChB, PhD         
Sponsors and Collaborators
University of California, San Francisco
Infectious Diseases Research Collaboration, Uganda
Makerere University
Kenya Medical Research Institute
Gilead Sciences
World Bank
National Institute of Allergy and Infectious Diseases (NIAID)
United States President's Emergency Plan for AIDS Relief
Investigators
Study Chair: Diane Havlir, MD University of California, San Francisco
Principal Investigator: Moses Kamya, MBChB, PhD Makerere University
Principal Investigator: Maya Petersen, PhD University of California, Berkeley
  More Information

Additional Information:
Publications:

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01864603     History of Changes
Other Study ID Numbers: SEARCH 
Study First Received: April 26, 2013
Last Updated: September 30, 2016
Health Authority: United States: Institutional Review Board
Uganda: National Council for Science and Technology
Uganda: National Drug Authority
Uganda: Research Ethics Committee
Kenya: Institutional Review Board
Kenya: Pharmacy and Poisons Board

Keywords provided by University of California, San Francisco:
HIV treatment and prevention
Tuberculosis
Community health campaign
PrEP

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

ClinicalTrials.gov processed this record on December 06, 2016