Options for Delivering Isoniazid-Rifapentine (3HP) for TB Prevention (3HP Options Implementation Trial)
NCT ID: NCT03934931
Last Updated: 2025-05-11
Study Results
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View full resultsBasic Information
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COMPLETED
NA
1656 participants
INTERVENTIONAL
2020-07-13
2025-01-13
Brief Summary
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Detailed Description
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Primary Objective: To compare the uptake of 3HP under three delivery strategies: 1) Facilitated DOT; 2) Facilitated SAT; and 3) Informed patient choice (using a decision aid) between facilitated DOT and facilitated SAT. The primary outcome will be defined as the proportion of eligible participants who accept treatment and take at least 11 of 12 doses of RPT/INH within 16 weeks of treatment initiation. Study staff will assess medication dosing using clinic records for participants taking 3HP by DOT and using a combination of 99DOTS (Everwell Health Solutions, India) digital medication adherence technology records and pill counts at refill visits for participants taking 3HP by SAT.
Secondary Objectives:
1. To estimate the costs and compare the cost-effectiveness of the three strategies for delivering 3HP.
2. To identify processes and contextual factors that influence patient acceptance and completion of 3HP under each delivery strategy.
3. To identify clinic-level barriers to adoption and implementation of 3HP under each delivery strategy.
4. To determine the proportion of patients for whom 3HP treatment is discontinued due to adverse events/intolerance.
5. To determine the cumulative 16-month incidence of active TB in each arm, categorized as definite (positive sputum Xpert MTB/RIF or culture) or probable (TB medications started at the discretion of a clinician, with evidence of subsequent improvement).
6. To determine the cumulative 28-month incidence of active TB in each arm, categorized as definite (positive sputum Xpert MTB/RIF or culture) or probable (TB medications started at the discretion of a clinician, with evidence of subsequent improvement).
Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
SINGLE
Study Groups
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Facilitated Directly Observed Therapy (DOT)
Facilitated DOT arm participants will attend the Mulago Immune Suppression Syndrome (ISS) clinic on a weekly basis to ingest 3HP medication under direct observation. DOT will be defined as a designated clinic staff member observing ingestion of each dose of 3HP. Additionally, participants randomized to facilitated DOT will receive: 1) DOT cards with instructions to present directly to the pharmacy for a pharmacy-only visit, without the need to wait in the general queue; 2) Automated short message service (SMS) or phone call reminders at no cost to participants the day before each appointment, 3) A fixed level of reimbursement (\~$5/visit) for each weekly visit, conditional on either directly observed therapy or evidence of an adverse event that would preclude further treatment.
Streamlined weekly DOT visits
Streamlined, weekly DOT clinic visits to have health worker observe medication ingestion and screen for side effects
Weekly DOT visit reminders
Weekly SMS or interactive voice response (IVR) phone call reminder for DOT clinic visits
Cost reimbursement DOT
Reimbursement of costs associated with weekly clinic visits (15,000 Ush/visit in Weeks 2-12)
Facilitated Self-Administered Therapy (SAT)
Facilitated SAT participants will take their 1st dose of medication under direct observation and be given a 4-week 3HP supply to take weekly via self-administration. Participants will return to the Mulago ISS clinic after completing their 5th dose to review adherence data with the clinic pharmacy technician and receive 5 additional 3HP doses (doses 7-11). At the scheduled refill visit (dose 6) and end-of-treatment visit (dose 12) participants will ingest 3HP via direct observation. Participants will also receive: 1) Free automated SMS reminders or phone call reminders before each scheduled dose; 2) Weekly check-ins inquiring about side effects via two-way SMS with a follow-up phone call depending on participant response, 3) Fixed level of reimbursement (\~$5/visit) for the refill/end-of-treatment visit, conditional on either directly observed therapy or evidence of an adverse event that would preclude further treatment.
99DOTS
99DOTS-based digital adherence technology to monitor and promote adherence
Weekly SAT dosing reminders/check-ins
Weekly SMS or IVR phone call dosing reminder/check-in for side effects
Cost reimbursement SAT
Reimbursement of costs associated with streamlined refill and end-of treatment clinic visits (15,000 Ush/visit in Weeks 6 and 12)
Patient Choice between facilitated DOT and facilitated SAT
Participants randomized to the Patient Choice between facilitated DOT and facilitated SAT arm will be offered a choice between arms 1 and 2. A research nurse will review each section of the decision aid with participants, discuss values and preferences, and, after addressing any questions, ask participants to select facilitated DOT or facilitated SAT. Participants will have the option to switch between DOT and SAT at any time. The reason for switching and time spent under each strategy will be recorded.
Streamlined weekly DOT visits
Streamlined, weekly DOT clinic visits to have health worker observe medication ingestion and screen for side effects
Weekly DOT visit reminders
Weekly SMS or interactive voice response (IVR) phone call reminder for DOT clinic visits
Cost reimbursement DOT
Reimbursement of costs associated with weekly clinic visits (15,000 Ush/visit in Weeks 2-12)
99DOTS
99DOTS-based digital adherence technology to monitor and promote adherence
Weekly SAT dosing reminders/check-ins
Weekly SMS or IVR phone call dosing reminder/check-in for side effects
Cost reimbursement SAT
Reimbursement of costs associated with streamlined refill and end-of treatment clinic visits (15,000 Ush/visit in Weeks 6 and 12)
Interventions
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Streamlined weekly DOT visits
Streamlined, weekly DOT clinic visits to have health worker observe medication ingestion and screen for side effects
Weekly DOT visit reminders
Weekly SMS or interactive voice response (IVR) phone call reminder for DOT clinic visits
Cost reimbursement DOT
Reimbursement of costs associated with weekly clinic visits (15,000 Ush/visit in Weeks 2-12)
99DOTS
99DOTS-based digital adherence technology to monitor and promote adherence
Weekly SAT dosing reminders/check-ins
Weekly SMS or IVR phone call dosing reminder/check-in for side effects
Cost reimbursement SAT
Reimbursement of costs associated with streamlined refill and end-of treatment clinic visits (15,000 Ush/visit in Weeks 6 and 12)
Eligibility Criteria
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Inclusion Criteria
* Weight ≥40kg
* Age 18 years or older
* Capacity to provide informed consent in English or Luganda
Exclusion Criteria
* Actively taking an antiretroviral medication contraindicated for use with rifapentine under contemporary WHO or Ugandan policy
* Contact of a TB patient with known resistance to isoniazid or rifamycins
* Women who are pregnant, breast feeding or intending to get pregnant in the next 120 days
* Prisoners
* Previously completed treatment for active TB or at least 6 months of isoniazid preventive therapy within past 2 years
* Not intending to remain within 25 km of the Mulago ISS clinic during the study period or to receive further care at the Mulago ISS clinic
* Lack of access to a mobile telephone or lack of willingness to receive SMS reminders
* Pre-existing documentation of clinical liver disease.
* History of sensitivity or intolerance to isoniazid or rifamycins
* Another household member already enrolled in the study (household members cannot be effectively randomized to different arms)
* Actively taking medication contraindicated for use with rifamycin (e.g., warfarin, phenytoin)
Mixed methods and health economic sub-studies will include a subset of participants enrolled in the trial, as well as clinic administrators and clinicians (clinical officer, doctor, nurse or pharmacist) involved in 3HP delivery at the Mulago ISS clinic.
18 Years
100 Years
ALL
Yes
Sponsors
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Makerere University
OTHER
Johns Hopkins Bloomberg School of Public Health
OTHER
University of Colorado, Denver
OTHER
National Heart, Lung, and Blood Institute (NHLBI)
NIH
University of California, San Francisco
OTHER
Responsible Party
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Principal Investigators
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Adithya Cattamanchi, MD
Role: PRINCIPAL_INVESTIGATOR
University of California, San Francisco
David W Dowdy, PhD
Role: PRINCIPAL_INVESTIGATOR
Johns Hopkins Bloomberg School of Public Health
Locations
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Mulago Immune Suppression Syndrome (ISS) Clinic
Kampala, , Uganda
Countries
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References
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Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Document Type: Informed Consent Form
Other Identifiers
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