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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 06/14/2021.

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

Clinicaltrials.gov identifier NCT03934931

Recruitment Status Recruiting

First Posted May 2, 2019

Last update posted August 6, 2020

Study Description

Brief summary:

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.

  • Condition or Disease:Tuberculosis
    Latent Tuberculosis
    HIV/AIDS
  • Intervention/Treatment: Other: Streamlined weekly DOT visits
    Other: Weekly DOT visit reminders
    Other: Cost reimbursement DOT
    Other: 99DOTS
    Other: Weekly SAT dosing reminders/check-ins
    Other: Cost reimbursement SAT
  • Phase: N/A
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 study enrollment. 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).

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 1656 participants
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Prevention
  • Official Title: Options for Delivering Isoniazid-Rifapentine (3HP) for TB Prevention: the 3HP Options Implementation Trial
  • Actual Study Start Date: July 2020
  • Estimated Primary Completion Date: October 2022
  • Estimated Study Completion Date: March 2023
Arms and interventions
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: 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)
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)
Outcome Measures
  • Primary Outcome Measures: 1. Acceptance and completion of 3HP [ Time Frame: Within 16 weeks of study enrollment ]
    The proportion of eligible participants who accept treatment and take at least 11 of 12 once weekly doses of RPT/INH within 16 weeks of study enrollment.
  • Secondary Outcome Measures: 1. 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.
  • 2. Visit Cost Reimbursement - overall [ Time Frame: Through study completion, an average of 16 weeks ]
    Proportion reimbursed overall
  • 3. Participant satisfaction [ Time Frame: Through study completion, an average of 16 weeks ]
    Mean score on participant satisfaction questionnaire
  • 4. Treatment acceptance [ Time Frame: Within 16 weeks of study enrollment ]
    Proportion of eligible PLHIV offered 3HP who accept to initiate treatment (by age, gender, CD4 stratum, viral load suppression).
  • 5. Treatment completion [ Time Frame: Within 16 weeks of study enrollment ]
    Proportion of participants who take at least 11 of 12 doses within 16 weeks of enrollment of those who take at least one dose of 3HP.
  • 6. 3HP discontinuation due to adverse events/intolerance [ Time Frame: Within 16 weeks of study enrollment ]
    Proportion of participants who initiate 3HP for whom treatment is discontinued due to adverse events or intolerance.
  • 7. 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 12-month post-treatment follow-up period ]
    Cumulative 16-month incidence of active TB in each arm
  • 8. Cost effectiveness (patient perspective) [ Time Frame: At the conclusion of the study period, estimated 3 years ]
    The incremental patient cost per DALY averted.
  • 9. 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.
  • 10. 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
  • 11. 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
  • 12. 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
  • 13. SMS or 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
  • 14. 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
  • 15. 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.
  • 16. 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.
  • 17. 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
  • 18. 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
  • 19. 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
  • 20. 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
  • 21. 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
  • 22. Costs of preventive services [ Time Frame: Through study completion, an average of 16 weeks ]
    Mean total participant costs related to TB preventive care services
  • 23. 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.
  • 24. 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
Eligibility Criteria
  • Ages Eligible for Study: 18 to 100 Years (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: Yes
Criteria

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.

Contacts and Locations
Contacts

Contact: Adithya Cattamanchi, MD +1-415-206-5489 adithya.cattamanchi@ucsf.edu

Locations

Uganda
Mulago Immune Suppression Syndrome (ISS) Clinic
Kampala

Sponsors and Collaborators

University of California, San Francisco

Makerere University

Johns Hopkins Bloomberg School of Public Health

University of Colorado, Denver

Investigators

Principal Investigator: Adithya Cattamanchi, MD University of California, San Francisco

Principal Investigator: David W Dowdy, PhD Johns Hopkins Bloomberg School of Public Health

More Information