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Simplified Isoniazid Preventive Therapy Strategy to Reduce TB Burden (SEARCH-IPT)

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ClinicalTrials.gov Identifier: NCT03315962
Recruitment Status : Recruiting
First Posted : October 20, 2017
Last Update Posted : August 11, 2020
Sponsor:
Collaborators:
Makerere University
National Institute of Allergy and Infectious Diseases (NIAID)
Cipla Ltd.
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
The failure to use isoniazid (INH) preventative therapy (IPT) in HIV-infected individuals in Sub-Saharan Africa represents one of the single biggest implementation gaps between evidence and practice in today's response to the HIV epidemic. The proposed study will evaluate the effectiveness of a multi-component intervention to improve IPT uptake in two regions of Uganda. The overall objective of this study is to determine if a multi-component implementation intervention (SPIRIT) that targets District Health Officers (DHOs) can increase IPT initiation and completion among HIV-infected persons, and decrease tuberculosis (TB) incidence, as compared to country standard practices, in a cluster randomized trial in Uganda.

Condition or disease Intervention/treatment Phase
Tuberculosis HIV/AIDS Behavioral: SPIRIT Intervention Combination Product: Single Pill Combination Not Applicable

Detailed Description:

[INTRODUCTION]

The failure to use isoniazid (INH) preventative therapy (IPT) in HIV-infected individuals in Sub-Saharan Africa represents one of the single biggest implementation gaps between evidence and practice in today's response to the HIV epidemic. The proposed study will evaluate the effectiveness of a multi-component intervention to improve IPT uptake in two regions of Uganda. The overall objective of this study is to determine if a multi-component implementation intervention (SPIRIT) that targets District Health Officers (DHOs) can increase IPT initiation and completion among HIV-infected persons, and decrease TB incidence, as compared to country standard practices, in a cluster randomized trial in Uganda.

[OBJECTIVES]

Aim 1: Determine if the SPIRIT intervention increases IPT initiation. The investigators will form 14 groups of 4-7 District Health Officers and randomize half to the SPIRIT intervention and half to control (country standard) in a cluster randomized trial. The primary outcome will be the proportion of HIV-infected adults newly enrolled in HIV care over the 36 months following intervention start who receive a prescription for INH in health facilities overseen by DHOs participating in the SPIRIT trial. In all DHO groups the primary outcome will be measured over three years. The investigators will use health information systems already in place to collect data about visits, IPT eligibility and IPT initiation. For secondary outcomes, the investigators will conduct pre-/post-intervention surveys and focus group discussions to assess changes in knowledge, attitudes and practices regarding IPT among the DHOs, TB support staff, and front line health workers in intervention and control groups, to assess mechanisms through which the intervention achieves outcomes.

Aim 2: Evaluate the effect of the SPIRIT intervention on IPT completion and TB incidence. Even if the intervention increases IPT initiation, quantifying actual use of IPT by patients and downstream effects on population health status (e.g. reduction in TB incidence) are important to assess impact and thereby enable policy makers to prioritize this intervention more widely. A subset of adult patients who received a prescription for IPT will be randomly sampled to measure adherence through hair levels of INH (direct measure of IPT completion) and TB incidence (population health measure). IPT completion and TB incidence will also be measured on the overall population of HIV-positive adults in care at health facilities overseen by the DHOs. Within the SPIRIT intervention arm, there is a nested trial for single pill combination (SPC) of INH/B6/Trimethoprim-sulfamethoxazole (TMP-SMX) vs. no-SPC for IPT.

Aim 3: Evaluate for indirect effects of the SPIRIT intervention on the prescribing of IPT to child (≤14 years of age) household contacts of active TB cases, and HIV-infected children (12 months to 14 years of age). The investigators hypothesize that IPT prescribing for child (≤14 years of age) household contacts of adults with active TB disease and for HIV-infected children (12 months to 14 years) will increase in SPIRIT intervention compared to control groups, as an indirect effect on DHO support for IPT implementation, IPT prescribing practices and patient perceptions of IPT.

Aim 4: Evaluate the cost and cost-effectiveness of SPIRIT. Using effectiveness measures obtained in Aims 1 and 2, and standard time and motion and costing methods, the investigators will estimate the cost and cost-effectiveness of SPIRIT vs. standard of care in our sampled population from Aim 2. Outcomes of interest will include program costs per: a) IPT initiation b) IPT completion and c) TB case averted.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1800 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Simplified Isoniazid Preventive Therapy (SPIRIT) Strategy to Reduce TB Burden
Actual Study Start Date : November 15, 2017
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Aim 1: DHO Intervention Arm
A selection of DHO or TB district supervisors that are randomized to the multicomponent SPIRIT intervention.
Behavioral: SPIRIT Intervention
The intervention will include implementing a teaching collaborative among group of DHOs and TB Supervisors, enabling text messaging between DHOs and front line providers, and establishing a report collaborative where DHOs will receive feedback on the performance of their district in administering IPT compared to other districts.

No Intervention: Aim 1: DHO Control Arm
A selection of DHO or TB district supervisors that are randomized to the country standard of care, but not to receive the study intervention.
Experimental: Aim 2: SPC Intervention Arm
Individuals randomized to receive the Single Pill Combination (SPC) for IPT who reside in districts where the SPIRIT intervention is being implemented.
Combination Product: Single Pill Combination
Among the districts randomized to the DHO Intervention Arm, a sub-sample of individuals in the district who are eligible for IPT will receive a single pill combination (SPC) of INH/B6/TMP-SMX for IPT. The control group will receive non-coformulated INH, B6 and TMP-SMX for IPT.

No Intervention: Aim 2: Non-SPC Control Arm
Individuals randomized to receive the non-Single Pill Combination (SPC) for IPT who reside in districts where the SPIRIT intervention is being implemented.
No Intervention: Aim 2: Adherence Sub-Study Observation
Individuals who are prescribed INH and reside in districts where the DHO has been enrolled in the SEARCH-IPT study will undergo observation for adherence to their INH regimen through testing hair samples, questionnaires, and clinic chart review.



Primary Outcome Measures :
  1. Proportion of eligible HIV-infected adults over the 36 months following intervention start who receive a prescription for INH in health facilities overseen by DHOs participating in the SPIRIT Trial [ Time Frame: 36 Months ]
    Aim 1: Primary Outcome


Secondary Outcome Measures :
  1. Changes in DHO and providers' knowledge and attitudes related to IPT in both intervention and control arms over time, as measured by quantitative surveys and data from focus group discussions. [ Time Frame: Baseline, 2-4, 6, 12, 18, 24, 30, and 36 Months post enrollment ]
    Aim 1: Secondary Outcome

  2. Measures of social influence of DHOs on frontline providers own attitudes and practices in the intervention vs. control arms. [ Time Frame: Baseline, 2-4, 6, 12, 18, 24, 30, and 36 Months post enrollment ]
    Aim 1: Secondary outcome. Measures of social influence will include perceptions of DHO credibility by frontline providers and level of exposure to DHO influence (via assessment of quality and quantity of communications from DHOs). These measures will be obtained through surveys with DHOs and frontline providers, text messaging frequency and content, and focus group discussions with DHOs and frontline providers.

  3. IPT uptake stratified by nested randomization to SPC vs. non-coformulated INH/B6 and TMP-SMX. [ Time Frame: 12 months after being IPT-Eligible ]
    Aim 2: Secondary Outcome

  4. IPT completion stratified by nested randomization to SPC vs. non-coformulated INH/B6 and TMP-SMX. [ Time Frame: 6 Months after IPT Initiation ]
    Aim 2: Secondary outcome

  5. Measurement of IPT adherence as measured by INH drug concentration (ng/mg) in hair samples among a sample of IPT initiators, and sufficient INH refill visits to complete 180 doses of INH. [ Time Frame: 3 and 6-months after IPT initiation ]
    Aim 2: Adherence Outcome

  6. Two-year cumulative incidence of TB among HIV-positive adults at health facilities overseen by DHOs participating in the SEARCH-IPT Trial. [ Time Frame: 24 Months ]
    Aim 2: TB Incidence Outcome

  7. Proportion of children who receive a prescription for INH within 12 months of being IPT-eligible at health facilities overseen by DHOs participating in the SEARCH-IPT Trial. [ Time Frame: 12 Months after becoming IPT-eligible ]
    Aim 3: Primary Outcome

  8. IPT completion rates among children who initiate IPT in SPIRIT intervention vs. control communities participating in the SEARCH-IPT Trial. [ Time Frame: 24 months ]
    Aim 3: Secondary outcome

  9. Childhood TB incidence in SPIRIT intervention vs. control communities participating in the SEARCH-IPT Trial. [ Time Frame: 24 months ]
    Aim 3: Secondary outcome

  10. Cost effectiveness of the SPIRIT intervention on IPT Initiation. [ Time Frame: 24 Months ]
    Aim 4: Primary Outcome. The cost-effectiveness analysis will include a measurement of program costs per person starting IPT.

  11. Cost effectiveness of the SPIRIT intervention on IPT completion. [ Time Frame: 24 Months ]
    Aim 4: Secondary Outcome. The cost-effectiveness analysis will include a measurement of program costs per person completing IPT.

  12. Cost effectiveness of the SPIRIT intervention on TB case averted. [ Time Frame: 24 Months ]
    Aim 4: Secondary Outcome. The cost-effectiveness analysis will include a measurement of program costs per TB case averted.

  13. Cost effectiveness of the SPIRIT intervention on DALYs averted. [ Time Frame: 24 Months ]
    Aim 4: Secondary Outcome. The cost-effectiveness analysis will include a measurement of program costs per Disability Adjusted Life Year (DALY) averted.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

AIM 1 - Spirit Intervention:

Inclusion Criteria:

  • District Health Officer or TB District Supervisor (or other DHO-appointed TB focal person) in Uganda.
  • By definition, the DHO or TB District Supervisor are all ≥18 years of age.

Exclusion Criteria:

  • Planned departure from position as DHO or TB District Supervisor prior to randomization.
  • DHOs from Kampala and Wakiso districts, Uganda.

AIM 2 - IPT Adherence & TB Incidence in the SPIRIT Trial

Inclusion Criteria:

  • Aged ≥15 years;
  • Residence in Uganda
  • HIV-infected (HIV antibody positive)
  • Prescribed INH during the SPIRIT trial study period

Exclusion Criteria:

  • Ineligible for IPT by Uganda Ministry of Health guidelines
  • Prior IPT completion
  • Ongoing treatment for active TB disease
  • Pregnancy or planning a pregnancy during the study period

AIM 3 - IPT use among Children: Evaluation of indirect effects of the SPIRIT Intervention

Inclusion criteria (by chart review only):

  • HIV-infected child age 12 months - 14 years; or
  • Child (≤14 years of age) identified as a household contact of an adult with active TB disease by Ministry of Health clinic;
  • Attendance at a clinic within a Ugandan District participating in the SPIRIT (Aim 1) cluster randomized trial

Exclusion criteria (by chart review only):

  • Ineligible for IPT by Uganda Ministry of Health guidelines
  • Prior IPT completion
  • Ongoing treatment for active TB disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03315962


Contacts
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Contact: Canice Christian, MS 415-476-4082 ext 206-3321 canice.christian@ucsf.edu

Locations
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Uganda
Infectious Diseases Research Collaboration Recruiting
Kampala, Uganda
Contact: Elijah Kakande, MBChB       rkakande@idrc-uganda.org   
Principal Investigator: Moses R. Kamya, MBChB, PhD         
Sponsors and Collaborators
University of California, San Francisco
Makerere University
National Institute of Allergy and Infectious Diseases (NIAID)
Cipla Ltd.
Investigators
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Principal Investigator: Diane Havlir, MD University of California, San Francisco
Study Chair: Gabriel Chamie, MD, MPH University of California, San Francisco
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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03315962    
Other Study ID Numbers: 16-21030
R01AI125000 ( U.S. NIH Grant/Contract )
First Posted: October 20, 2017    Key Record Dates
Last Update Posted: August 11, 2020
Last Verified: August 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections