Options for Delivering Isoniazid-Rifapentine (3HP) for TB Prevention (3HP Options Implementation Trial)

November 16, 2023 updated by: University of California, San Francisco

Options for Delivering Isoniazid-Rifapentine (3HP) for TB Prevention: the 3HP Options Implementation Trial

The Options for Delivering Isoniazid-Rifapentine (3HP) for TB Prevention (3HP Options Implementation Trial) study will be a three-arm, open-label, parallel, randomized trial. This hybrid effectiveness-implementation trial will be conducted among people living with HIV infection (PLHIV) enrolled in HIV/AIDS care at the Mulago Immune Suppression Syndrome (i.e., HIV/AIDS) clinic in Kampala, Uganda. The overall objective of this study is to identify a patient-centered delivery strategy that will facilitate acceptance and completion of a three-month (12-dose) regimen of weekly rifapentine (RPT) and isoniazid (INH) by PLHIV enrolled in routine HIV/AIDS care in a high HIV/TB burden country. The primary outcome will be acceptance and completion of 3HP. Additional objectives will be to evaluate the implementation and cost-effectiveness of each delivery strategy.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

The overall objective of this study is to identify a patient-centered strategy that will facilitate 3HP uptake by PLHIV in the context of routine HIV/AIDS care in a high HIV/TB burden country. The investigators' central hypothesis is that offering PLHIV an informed choice between directly observed therapy (DOT) and self-administered therapy (SAT) delivery strategies that are optimized to overcome key barriers to treatment adherence will result in greater acceptance and completion of 3HP. To test this hypothesis, the investigators will conduct a pragmatic randomized trial of three optimized strategies for delivering 3HP. Eligible participants will be randomized to one of three arms to receive latent tuberculosis infection (LTBI) treatment with once weekly INH and RPT for 12 weeks given by either facilitated DOT, facilitated SAT, or an informed choice between facilitated DOT and facilitated SAT (with the assistance of a decision aid tool).

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).

Study Type

Interventional

Enrollment (Actual)

1656

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Uganda
      • Kampala, Uganda
        • Mulago Immune Suppression Syndrome (ISS) Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • HIV-positive client engaged in care at the Mulago ISS clinic
  • Weight ≥40kg
  • Age 18 years or older
  • Capacity to provide informed consent in English or Luganda

Exclusion Criteria:

  • Suspicion of active TB based on positive World Health Organization (WHO) symptom screen AND elevated point-of-care (POC) C-reactive protein (CRP), or current or planned TB treatment
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Other: Streamlined weekly DOT visits
Streamlined, weekly DOT clinic visits to have health worker observe medication ingestion and screen for side effects
Other: Weekly DOT visit reminders
Weekly SMS or interactive voice response (IVR) phone call reminder for DOT clinic visits
Other: Cost reimbursement DOT
Reimbursement of costs associated with weekly clinic visits (15,000 Ush/visit in Weeks 2-12)
Experimental: 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.
Other: 99DOTS
99DOTS-based digital adherence technology to monitor and promote adherence
Other: Weekly SAT dosing reminders/check-ins
Weekly SMS or IVR phone call dosing reminder/check-in for side effects
Other: 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)
Experimental: 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.
Other: Streamlined weekly DOT visits
Streamlined, weekly DOT clinic visits to have health worker observe medication ingestion and screen for side effects
Other: Weekly DOT visit reminders
Weekly SMS or interactive voice response (IVR) phone call reminder for DOT clinic visits
Other: Cost reimbursement DOT
Reimbursement of costs associated with weekly clinic visits (15,000 Ush/visit in Weeks 2-12)
Other: 99DOTS
99DOTS-based digital adherence technology to monitor and promote adherence
Other: Weekly SAT dosing reminders/check-ins
Weekly SMS or IVR phone call dosing reminder/check-in for side effects
Other: 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Participants Who Accepted and Completed 3HP
Time Frame: Within 16 weeks of treatment initiation
The count of eligible participants who accept treatment and take at least 11 of 12 once weekly doses of rifapentine (RPT)/isoniazid (INH) within 16 weeks of treatment initiation divided by the count of those randomized.
Within 16 weeks of treatment initiation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Visit Cost Reimbursement
Time Frame: On the same day as each 3HP clinic visit throughout study completion, an average of 16 weeks
Proportion reimbursed on the same day as each 3HP clinic visit
On the same day as each 3HP clinic visit throughout study completion, an average of 16 weeks
Proportion of Participants Who Accepted 3HP Treatment
Time Frame: Within 16 weeks of treatment initiation
The count of eligible people living with HIV (PLHIV) offered 3HP who accept to initiate treatment (by age, gender, CD4 stratum, viral load suppression) divided by the count of those randomized.
Within 16 weeks of treatment initiation
Proportion of Participants Who Completed 3HP Treatment
Time Frame: Within 16 weeks of treatment initiation
Count of participants who take at least 11 of 12 doses within 16 weeks of treatment initiation divided by the count those who take at least one dose of 3HP.
Within 16 weeks of treatment initiation
Proportion of People Who Discontinued 3HP Treatment Due to Adverse Events/Intolerance
Time Frame: Within 16 weeks of treatment initiation
Count of participants for whom treatment is discontinued due to adverse events or intolerance divided by the count of those who initiated 3HP.
Within 16 weeks of treatment initiation
Cumulative Incidence of Tuberculosis (TB)
Time Frame: from date of 3HP treatment completion (11/12 doses) or once reached 16 weeks (regardless of number of doses taken) until time of active TB diagnosis or treatment initiation, death, loss to follow-up or end of the 12-month post-treatment follow-up period
Cumulative 16-month incidence of active TB in each arm
from date of 3HP treatment completion (11/12 doses) or once reached 16 weeks (regardless of number of doses taken) until time of active TB diagnosis or treatment initiation, death, loss to follow-up or end of the 12-month post-treatment follow-up period
Cumulative Incidence of TB
Time Frame: from date of 3HP treatment completion (11/12 doses) or once reached 16 weeks (regardless of number of doses taken) until time of active TB diagnosis or treatment initiation, death, loss to follow-up or end of the 24-month post-treatment follow-up period
Cumulative 28-month incidence of active TB in each arm
from date of 3HP treatment completion (11/12 doses) or once reached 16 weeks (regardless of number of doses taken) until time of active TB diagnosis or treatment initiation, death, loss to follow-up or end of the 24-month post-treatment follow-up period
Cost Effectiveness (Patient Perspective)
Time Frame: At the conclusion of the study period, estimated 3 years
The incremental patient cost per disability-adjusted life year (DALY) averted.
At the conclusion of the study period, estimated 3 years
Cost Effectiveness (Health System Perspective)
Time Frame: At the conclusion of the study period, estimated 3 years
The incremental health system cost per disability-adjusted life year (DALY) averted.
At the conclusion of the study period, estimated 3 years
Cost Effectiveness (Overall Perspective)
Time Frame: At the conclusion of the study period, estimated 3 years
Incremental cost of each delivery strategy per disability adjusted life year (DALY) averted.
At the conclusion of the study period, estimated 3 years
Visit Cost Reimbursement - Overall
Time Frame: Through study completion, an average of 16 weeks
Proportion reimbursed overall
Through study completion, an average of 16 weeks
Time to Complete Clinic Visit - Mean Minutes
Time Frame: On the same day as each 3HP clinic visit throughout study completion, an average of 16 weeks
Mean number of minutes for each DOT/refill visit
On the same day as each 3HP clinic visit throughout study completion, an average of 16 weeks
Time to Complete Clinic Visit - Median Minutes
Time Frame: On the same day as each 3HP clinic visit throughout study completion, an average of 16 weeks
Median number of minutes for each DOT/refill visit
On the same day as each 3HP clinic visit throughout study completion, an average of 16 weeks
Short Messages Service (SMS) or Interactive Voice Response (IVR) Phone Call Reminders Delivered - Clinic Visits
Time Frame: The day before each 3HP clinic visit throughout study completion, an average of 16 weeks
Proportion of SMS or IVR phone call reminders delivered to participants for clinic visits
The day before each 3HP clinic visit throughout study completion, an average of 16 weeks
Screening for Active TB
Time Frame: On the same day as each 3HP clinic visit throughout study completion, an average of 16 weeks
Proportion of participants screened for active TB during DOT or refill visits
On the same day as each 3HP clinic visit throughout study completion, an average of 16 weeks
Screening for Side Effects
Time Frame: On the same day as each 3HP clinic visit throughout study completion, an average of 16 weeks
Proportion of participants screened for side effects during DOT or refill visits.
On the same day as each 3HP clinic visit throughout study completion, an average of 16 weeks
Dosing Confirmation Via 99DOTS (SAT Only)
Time Frame: On the same day as each scheduled dose throughout study completion, an average of 16 weeks
Proportion of doses confirmed using digital adherence technology. Doses directly observed (i.e., during initial or refill visits) will not be included in the denominator.
On the same day as each scheduled dose throughout study completion, an average of 16 weeks
SMS or IVR Phone Call Reminders Delivered - Medication Dosing (SAT Only)
Time Frame: The day before each scheduled dose throughout study completion, an average of 16 weeks
Proportion of SMS or IVR phone call reminders delivered to participants for medication dosing
The day before each scheduled dose throughout study completion, an average of 16 weeks
SMS or IVR Phone Calls Delivered - Weekly check-in (SAT Only)
Time Frame: On the same day as each scheduled dose throughout study completion, an average of 16 weeks
Proportion of weekly SMS or IVR phone call check-ins delivered to participants
On the same day as each scheduled dose throughout study completion, an average of 16 weeks
SMS or IVR Phone Call Reminders Delivered - Missed Dose (SAT Only)
Time Frame: 24 hours after missed scheduled dose throughout study completion, an average of 16 weeks
Proportion of SMS or IVR phone call reminders delivered to participants following missed doses
24 hours after missed scheduled dose throughout study completion, an average of 16 weeks
SMS or IVR Phone Call Missed Appointment Reminders Delivered
Time Frame: 24 hours after missed scheduled appointment throughout study completion, an average of 16 weeks
Proportion of SMS or IVR phone call reminders delivered to participants following missed appointments
24 hours after missed scheduled appointment throughout study completion, an average of 16 weeks
Follow up (Phone Calls or Home Visits) for Negative Response to Weekly SMS or IVR Phone Call check-in (SAT Only)
Time Frame: 24 hours after negative response throughout study completion, an average of 16 weeks
Proportion of participants who receive appropriate follow-up (phone call or home visit) for lack of response/negative response to weekly check-in SMS or IVR phone call
24 hours after negative response throughout study completion, an average of 16 weeks
Costs of Preventive Services
Time Frame: Through study completion, an average of 16 weeks
Mean total participant costs related to TB preventive care services
Through study completion, an average of 16 weeks
Participant Satisfaction
Time Frame: Through study completion, an average of 16 weeks
Mean score on participant satisfaction questionnaire
Through study completion, an average of 16 weeks
Barriers to 3HP Delivery From the Provider/Clinic Perspective
Time Frame: At the conclusion of the study period, estimated 3 years
Thematic interpretation of provider- and clinic-level barriers to care from provider focus group discussions.
At the conclusion of the study period, estimated 3 years
Barriers to 3HP Completion From the Patient Perspective
Time Frame: Through study completion, an average of 16 weeks
Thematic interpretation of barriers to 3HP completion from patient interviews
Through study completion, an average of 16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

University of Colorado, Denver
National Heart, Lung, and Blood Institute (NHLBI)
Johns Hopkins Bloomberg School of Public Health
Makerere University

Investigators

  • Principal Investigator: Adithya Cattamanchi, MD, University of California, San Francisco
  • Principal Investigator: David W Dowdy, PhD, Johns Hopkins Bloomberg School of Public Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 13, 2020

Primary Completion (Actual)

September 29, 2022

Study Completion (Estimated)

November 8, 2024

Study Registration Dates

First Submitted

April 22, 2019

First Submitted That Met QC Criteria

April 29, 2019

First Posted (Actual)

May 2, 2019

Study Record Updates

Last Update Posted (Estimated)

November 20, 2023

Last Update Submitted That Met QC Criteria

November 16, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R01HL144406 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Provided upon request

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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