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
|Condition or disease||Intervention/treatment||Phase|
|Tuberculosis HIV/AIDS||Behavioral: SPIRIT Intervention Combination Product: Single Pill Combination||Not Applicable|
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||1800 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
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.
- 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
- 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
- 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.
- 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
- 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
- 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
- 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
- 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
- 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
- Childhood TB incidence in SPIRIT intervention vs. control communities participating in the SEARCH-IPT Trial. [ Time Frame: 24 months ]Aim 3: Secondary outcome
- 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.
- 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.
- 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.
- 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.
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
|Contact: Canice Christian, MS||415-476-4082 ext firstname.lastname@example.org|
|Infectious Diseases Research Collaboration||Recruiting|
|Contact: Elijah Kakande, MBChB email@example.com|
|Principal Investigator: Moses R. Kamya, MBChB, PhD|
|Principal Investigator:||Diane Havlir, MD||University of California, San Francisco|
|Study Chair:||Gabriel Chamie, MD, MPH||University of California, San Francisco|