TuberculosisNCT03934931

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

A study testing Streamlined weekly DOT visits, Weekly DOT visit reminders and Cost reimbursement DOT in people with Tuberculosis and Latent Tuberculosis, run by University of California, San Francisco at 1 site in Uganda.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 100 yearsHealthy volunteers can take part
Conditions the study is for: Tuberculosis, Latent Tuberculosis, HIV/AIDS
What is being tested?: Streamlined weekly DOT visits, Weekly DOT visit reminders and Cost reimbursement DOT
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1,656 participants
Where: 1 siteUganda
Study dates: 13 Jul 2020to 13 Jan 2025
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 100 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 13Show fewer

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.

Trial locations and contacts

1 site in 1 country.

Uganda1 site

Mulago Immune Suppression Syndrome (ISS) Clinic
Kampala

Other trials in Uganda

About this study

Official title: 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.

Read the 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:

To estimate the costs and compare the cost-effectiveness of the three strategies for delivering 3HP.
To identify processes and contextual factors that influence patient acceptance and completion of 3HP under each delivery strategy.
To identify clinic-level barriers to adoption and implementation of 3HP under each delivery strategy.
To determine the proportion of patients for whom 3HP treatment is discontinued due to adverse events/intolerance.
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).
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: Tuberculosis, Latent Tuberculosis, HIV/AIDS
Being tested: Streamlined weekly DOT visits, Weekly DOT visit reminders, Cost reimbursement DOT, 99DOTS, Weekly SAT dosing reminders/check-ins
Keywords: latent tuberculosis, tuberculosis, HIV/AIDS, implementation science, Uganda, 3HP, shared decision making, rifapentine
Medical subject headings: Tuberculosis, Latent Tuberculosis, Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Streamlined weekly DOT visitsOther
Streamlined, weekly DOT clinic visits to have health worker observe medication ingestion and screen for side effects
Weekly DOT visit remindersOther
Weekly SMS or interactive voice response (IVR) phone call reminder for DOT clinic visits
Cost reimbursement DOTOther
Reimbursement of costs associated with weekly clinic visits (15,000 Ush/visit in Weeks 2-12)
99DOTSOther
99DOTS-based digital adherence technology to monitor and promote adherence
Weekly SAT dosing reminders/check-insOther
Weekly SMS or IVR phone call dosing reminder/check-in for side effects
Cost reimbursement SATOther
Reimbursement of costs associated with streamlined refill and end-of treatment clinic visits (15,000 Ush/visit in Weeks 6 and 12)

Study groups in NCT03934931
Study group	Role	What they receive
Facilitated Directly Observed Therapy (DOT)	Experimental	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. Receives: Other: Streamlined weekly DOT visits; Other: Weekly DOT visit reminders; Other: Cost reimbursement DOT
Facilitated Self-Administered Therapy (SAT)	Experimental	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. Receives: Other: 99DOTS; Other: Weekly SAT dosing reminders/check-ins; Other: Cost reimbursement SAT
Patient Choice between facilitated DOT and facilitated SAT	Experimental	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. Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

Proportion of Participants Who Accepted and Completed 3HP
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.
Measured: Within 16 weeks of treatment initiation

Secondary outcomes (25)

Proportion of Participants Who Accepted 3HP Treatment
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.
Measured: Within 16 weeks of treatment initiation
Proportion of Participants Who Completed 3HP Treatment
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.
Measured: Within 16 weeks of treatment initiation
Proportion of People Who Discontinued 3HP Treatment Due to Adverse Events/Intolerance
Count of participants for whom treatment is discontinued due to adverse events or intolerance divided by the count of those who initiated 3HP.
Measured: Within 16 weeks of treatment initiation
Cumulative Incidence of Tuberculosis (TB)
Cumulative 16-month incidence of active TB in each arm
Measured: 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
Cumulative 28-month incidence of active TB in each arm
Measured: 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)
The incremental patient cost per disability-adjusted life year (DALY) averted.
Measured: At the conclusion of the study period, estimated 3 years
Cost Effectiveness (Health System Perspective)
The incremental health system cost per disability-adjusted life year (DALY) averted.
Measured: At the conclusion of the study period, estimated 3 years
Cost Effectiveness (Overall Perspective)
Incremental cost of each delivery strategy per disability adjusted life year (DALY) averted.
Measured: At the conclusion of the study period, estimated 3 years
Visit Cost Reimbursement - Overall
Proportion reimbursed overall
Measured: Through study completion, an average of 16 weeks
Visit Cost Reimbursement
Proportion reimbursed on the same day as each 3HP clinic visit
Measured: On the same day as each 3HP clinic visit throughout study completion, an average of 16 weeks
Time to Complete Clinic Visit - Mean Minutes
Mean number of minutes for each DOT/refill visit
Measured: On the same day as each 3HP clinic visit throughout study completion, an average of 16 weeks
Time to Complete Clinic Visit - Median Minutes
Median number of minutes for each DOT/refill visit
Measured: 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
Proportion of SMS or IVR phone call reminders delivered to participants for clinic visits
Measured: The day before each 3HP clinic visit throughout study completion, an average of 16 weeks
Screening for Active TB
Proportion of participants screened for active TB during DOT or refill visits
Measured: On the same day as each 3HP clinic visit throughout study completion, an average of 16 weeks
Screening for Side Effects
Proportion of participants screened for side effects during DOT or refill visits.
Measured: On the same day as each 3HP clinic visit throughout study completion, an average of 16 weeks
Dosing Confirmation Via 99DOTS (SAT Only)
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.
Measured: 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)
Proportion of SMS or IVR phone call reminders delivered to participants for medication dosing
Measured: 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)
Proportion of weekly SMS or IVR phone call check-ins delivered to participants
Measured: 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)
Proportion of SMS or IVR phone call reminders delivered to participants following missed doses
Measured: 24 hours after missed scheduled dose throughout study completion, an average of 16 weeks
SMS or IVR Phone Call Missed Appointment Reminders Delivered
Proportion of SMS or IVR phone call reminders delivered to participants following missed appointments
Measured: 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)
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
Measured: 24 hours after negative response throughout study completion, an average of 16 weeks
Costs of Preventive Services
Mean total participant costs related to TB preventive care services
Measured: Through study completion, an average of 16 weeks
Participant Satisfaction
Mean score on participant satisfaction questionnaire
Measured: Through study completion, an average of 16 weeks
Barriers to 3HP Delivery From the Provider/Clinic Perspective
Thematic interpretation of provider- and clinic-level barriers to care from provider focus group discussions.
Measured: At the conclusion of the study period, estimated 3 years
Barriers to 3HP Completion From the Patient Perspective
Thematic interpretation of barriers to 3HP completion from patient interviews
Measured: Through study completion, an average of 16 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Jul 202013 Jan 2025

First posted2 May 2019
Study start13 Jul 2020
Primary completion29 Sep 2022
Study completion13 Jan 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (33)Papers the sponsor has linked to this study.
Other trials for TuberculosisStudies of the same condition, open and under way.
More trials run by University of California, San FranciscoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Investigator
Enrolment: 1,656 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03934931
Sponsor's protocol ID: R01HL144406
Other IDs: R01HL144406
Status last verified: May 2025
First submitted: 22 Apr 2019
Last updated: 11 May 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Provided upon request

Publications

TEMPRANO ANRS 12136 Study Group; Danel C, Moh R, Gabillard D, Badje A, Le Carrou J, Ouassa T, Ouattara E, Anzian A, Ntakpe JB, Minga A, Kouame GM, Bouhoussou F, Emieme A, Kouame A, Inwoley A, Toni TD, Ahiboh H, Kabran M, Rabe C, Sidibe B, Nzunetu G, Konan R, Gnokoro J, Gouesse P, Messou E, Dohoun L, Kamagate S, Yao A, Amon S, Kouame AB, Koua A, Kouame E, Ndri Y, Ba-Gomis O, Daligou M, Ackoundze S, Hawerlander D, Ani A, Dembele F, Kone F, Guehi C, Kanga C, Koule S, Seri J, Oyebi M, Mbakop N, Makaila O, Babatunde C, Babatounde N, Bleoue G, Tchoutedjem M, Kouadio AC, Sena G, Yededji SY, Assi R, Bakayoko A, Mahassadi A, Attia A, Oussou A, Mobio M, Bamba D, Koman M, Horo A, Deschamps N, Chenal H, Sassan-Morokro M, Konate S, Aka K, Aoussi E, Journot V, Nchot C, Karcher S, Chaix ML, Rouzioux C, Sow PS, Perronne C, Girard PM, Menan H, Bissagnene E, Kadio A, Ettiegne-Traore V, Moh-Semde C, Kouame A, Massumbuko JM, Chene G, Dosso M, Domoua SK, N'Dri-Yoman T, Salamon R, Eholie SP, Anglaret X. A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa. N Engl J Med. 2015 Aug 27;373(9):808-22. doi: 10.1056/NEJMoa1507198. Epub 2015 Jul 20.
PubMed 26193126
Dye C, Glaziou P, Floyd K, Raviglione M. Prospects for tuberculosis elimination. Annu Rev Public Health. 2013;34:271-86. doi: 10.1146/annurev-publhealth-031912-114431. Epub 2012 Dec 14.
PubMed 23244049
Getahun H, Granich R, Sculier D, Gunneberg C, Blanc L, Nunn P, Raviglione M. Implementation of isoniazid preventive therapy for people living with HIV worldwide: barriers and solutions. AIDS. 2010 Nov;24 Suppl 5:S57-65. doi: 10.1097/01.aids.0000391023.03037.1f. No abstract available.
PubMed 21079430
Namuwenge PM, Mukonzo JK, Kiwanuka N, Wanyenze R, Byaruhanga R, Bissell K, Zachariah R. Loss to follow up from isoniazid preventive therapy among adults attending HIV voluntary counseling and testing sites in Uganda. Trans R Soc Trop Med Hyg. 2012 Feb;106(2):84-9. doi: 10.1016/j.trstmh.2011.10.015. Epub 2011 Dec 10.
PubMed 22154974
Martinson NA, Barnes GL, Moulton LH, Msandiwa R, Hausler H, Ram M, McIntyre JA, Gray GE, Chaisson RE. New regimens to prevent tuberculosis in adults with HIV infection. N Engl J Med. 2011 Jul 7;365(1):11-20. doi: 10.1056/NEJMoa1005136.
PubMed 21732833
Sterling TR, Villarino ME, Borisov AS, Shang N, Gordin F, Bliven-Sizemore E, Hackman J, Hamilton CD, Menzies D, Kerrigan A, Weis SE, Weiner M, Wing D, Conde MB, Bozeman L, Horsburgh CR Jr, Chaisson RE; TB Trials Consortium PREVENT TB Study Team. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med. 2011 Dec 8;365(23):2155-66. doi: 10.1056/NEJMoa1104875.
PubMed 22150035
Podany AT, Bao Y, Swindells S, Chaisson RE, Andersen JW, Mwelase T, Supparatpinyo K, Mohapi L, Gupta A, Benson CA, Kim P, Fletcher CV; AIDS Clinical Trials Group A5279 Study Team. Efavirenz Pharmacokinetics and Pharmacodynamics in HIV-Infected Persons Receiving Rifapentine and Isoniazid for Tuberculosis Prevention. Clin Infect Dis. 2015 Oct 15;61(8):1322-7. doi: 10.1093/cid/civ464. Epub 2015 Jun 16.
PubMed 26082504
Weiner M, Egelund EF, Engle M, Kiser M, Prihoda TJ, Gelfond JA, Mac Kenzie W, Peloquin CA. Pharmacokinetic interaction of rifapentine and raltegravir in healthy volunteers. J Antimicrob Chemother. 2014 Apr;69(4):1079-85. doi: 10.1093/jac/dkt483. Epub 2013 Dec 15.
PubMed 24343893
Swindells S, Ramchandani R, Gupta A, Benson CA, Leon-Cruz J, Mwelase N, Jean Juste MA, Lama JR, Valencia J, Omoz-Oarhe A, Supparatpinyo K, Masheto G, Mohapi L, da Silva Escada RO, Mawlana S, Banda P, Severe P, Hakim J, Kanyama C, Langat D, Moran L, Andersen J, Fletcher CV, Nuermberger E, Chaisson RE; BRIEF TB/A5279 Study Team. One Month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis. N Engl J Med. 2019 Mar 14;380(11):1001-1011. doi: 10.1056/NEJMoa1806808.
PubMed 30865794
Belknap R, Holland D, Feng PJ, Millet JP, Cayla JA, Martinson NA, Wright A, Chen MP, Moro RN, Scott NA, Arevalo B, Miro JM, Villarino ME, Weiner M, Borisov AS; TB Trials Consortium iAdhere Study Team. Self-administered Versus Directly Observed Once-Weekly Isoniazid and Rifapentine Treatment of Latent Tuberculosis Infection: A Randomized Trial. Ann Intern Med. 2017 Nov 21;167(10):689-697. doi: 10.7326/M17-1150. Epub 2017 Nov 7.
PubMed 29114781
Liu X, Blaschke T, Thomas B, De Geest S, Jiang S, Gao Y, Li X, Buono EW, Buchanan S, Zhang Z, Huan S. Usability of a Medication Event Reminder Monitor System (MERM) by Providers and Patients to Improve Adherence in the Management of Tuberculosis. Int J Environ Res Public Health. 2017 Sep 25;14(10):1115. doi: 10.3390/ijerph14101115.
PubMed 28946683
Institute of Medicine (US) Committee on Quality of Health Care in America. Crossing the Quality Chasm: A New Health System for the 21st Century. Washington (DC): National Academies Press (US); 2001. Available from http://www.ncbi.nlm.nih.gov/books/NBK222274/
PubMed 25057539
Charles C, Gafni A, Whelan T. Shared decision-making in the medical encounter: what does it mean? (or it takes at least two to tango). Soc Sci Med. 1997 Mar;44(5):681-92. doi: 10.1016/s0277-9536(96)00221-3.
PubMed 9032835
Joosten EA, DeFuentes-Merillas L, de Weert GH, Sensky T, van der Staak CP, de Jong CA. Systematic review of the effects of shared decision-making on patient satisfaction, treatment adherence and health status. Psychother Psychosom. 2008;77(4):219-26. doi: 10.1159/000126073. Epub 2008 Apr 16.
PubMed 18418028
Stacey D, Legare F, Lewis K, Barry MJ, Bennett CL, Eden KB, Holmes-Rovner M, Llewellyn-Thomas H, Lyddiatt A, Thomson R, Trevena L. Decision aids for people facing health treatment or screening decisions. Cochrane Database Syst Rev. 2017 Apr 12;4(4):CD001431. doi: 10.1002/14651858.CD001431.pub5.
PubMed 28402085

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 11 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Options for Delivering Isoniazid-Rifapentine (3HP) for TB Prevention: the 3HP Options Implementation Trial
ClinicalTrials.gov ID: NCT03934931
Acronym / sponsor ID: R01HL144406
Conditions: Tuberculosis, Latent Tuberculosis, HIV/AIDS
Keywords: latent tuberculosis, tuberculosis, HIV/AIDS, implementation science, Uganda, 3HP, shared decision making, rifapentine
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,656 participants (actual)
Lead sponsor: University of California, San FranciscoUniversity, hospital or other
Collaborators: Makerere University, Johns Hopkins Bloomberg School of Public Health, University of Colorado, Denver, National Heart, Lung, and Blood Institute (NHLBI)
Study start: 13 Jul 2020 (actual)
Primary completion: 29 Sep 2022 (actual)
Study completion: 13 Jan 2025 (actual)
First posted: 2 May 2019 (actual)
Results: Posted 7 Nov 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Secondary Objectives:

To estimate the costs and compare the cost-effectiveness of the three strategies for delivering 3HP.
To identify processes and contextual factors that influence patient acceptance and completion of 3HP under each delivery strategy.
To identify clinic-level barriers to adoption and implementation of 3HP under each delivery strategy.
To determine the proportion of patients for whom 3HP treatment is discontinued due to adverse events/intolerance.
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).
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 design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (investigator)
Number of arms: 3

Arm	Type	Receives
Facilitated Directly Observed Therapy (DOT)	Experimental	Other: Streamlined weekly DOT visits, Other: Weekly DOT visit reminders, Other: Cost reimbursement DOTFacilitated 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.
Facilitated Self-Administered Therapy (SAT)	Experimental	Other: 99DOTS, Other: Weekly SAT dosing reminders/check-ins, Other: Cost reimbursement SATFacilitated 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.
Patient Choice between facilitated DOT and facilitated SAT	Experimental	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 SATParticipants 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.

Who may qualify

Ages: 18 to 100 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (13 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Streamlined weekly DOT visitsStreamlined, weekly DOT clinic visits to have health worker observe medication ingestion and screen for side effects	Other	Facilitated Directly Observed Therapy (DOT), Patient Choice between facilitated DOT and facilitated SAT
Weekly DOT visit remindersWeekly SMS or interactive voice response (IVR) phone call reminder for DOT clinic visits	Other	Facilitated Directly Observed Therapy (DOT), Patient Choice between facilitated DOT and facilitated SAT
Cost reimbursement DOTReimbursement of costs associated with weekly clinic visits (15,000 Ush/visit in Weeks 2-12)	Other	Facilitated Directly Observed Therapy (DOT), Patient Choice between facilitated DOT and facilitated SAT
99DOTS99DOTS-based digital adherence technology to monitor and promote adherence	Other	Facilitated Self-Administered Therapy (SAT), Patient Choice between facilitated DOT and facilitated SAT
Weekly SAT dosing reminders/check-insWeekly SMS or IVR phone call dosing reminder/check-in for side effects	Other	Facilitated Self-Administered Therapy (SAT), Patient Choice between facilitated DOT and facilitated SAT
Cost reimbursement SATReimbursement of costs associated with streamlined refill and end-of treatment clinic visits (15,000 Ush/visit in Weeks 6 and 12)	Other	Facilitated Self-Administered Therapy (SAT), Patient Choice between facilitated DOT and facilitated SAT

Primary outcome

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.

25 secondary outcomes

Proportion of Participants Who Accepted 3HP Treatment
Time frame: Within 16 weeks of treatment initiation
Proportion of Participants Who Completed 3HP Treatment
Time frame: 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
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 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
Cost Effectiveness (Patient Perspective)
Time frame: 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
Cost Effectiveness (Overall Perspective)
Time frame: At the conclusion of the study period, estimated 3 years
Visit Cost Reimbursement - Overall
Time frame: Through study completion, an average of 16 weeks
Visit Cost Reimbursement
Time frame: On the same day as each 3HP clinic visit throughout 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
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
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
Screening for Active TB
Time frame: 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
Dosing Confirmation Via 99DOTS (SAT Only)
Time frame: 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
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
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
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
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
Costs of Preventive Services
Time frame: Through study completion, an average of 16 weeks
Participant Satisfaction
Time frame: 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
Barriers to 3HP Completion From the Patient Perspective
Time frame: Through study completion, an average of 16 weeks

Results and safety

Results posted to the registry on 7 Nov 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Facilitated Directly Observed Therapy (DOT)	552	551
Facilitated Self-Administered Therapy (SAT)	552	552
Patient Choice Between Facilitated DOT and Facilitated SAT	552	552

Primary outcome: Proportion of Participants Who Accepted and Completed 3HP

Time frame: Within 16 weeks of treatment initiation. Number. Unit: proportion of participants

Measure	Facilitated Directly Observed Therapy (DOT) n = 551	Facilitated Self-Administered Therapy (SAT) n = 552	Patient Choice Between Facilitated DOT and Facilitated SAT n = 552
Value	0.946	0.922	0.944

Population analysed: 1,656 people were eligible and randomized. One participant was erroneously re-randomized (facilitated DOT arm) after an initial enrollment; data from their second randomization was excluded. 1,655 were included in the primary outcome analysis.

25 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected weekly over the course of 3HP treatment duration (up to 16 weeks after treatment initiation). Other adverse events reported at 4% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Facilitated Directly Observed Therapy (DOT)	3 of 551 (0.5%)	83 of 551 (15.1%)	1 of 551
Facilitated Self-Administered Therapy (SAT)	7 of 552 (1.3%)	86 of 552 (15.6%)	0 of 552
Patient Choice Between Facilitated DOT and Facilitated SAT	4 of 552 (0.7%)	76 of 552 (13.8%)	0 of 552

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 26193126TEMPRANO ANRS 12136 Study Group; Danel C, Moh R, Gabillard D, Badje A, Le Carrou J, Ouassa T, Ouattara E, Anzian A, Ntakpe JB, Minga A, Kouame GM, Bouhoussou F, Emieme A, Kouame A, Inwoley A, Toni TD, Ahiboh H, Kabran M, Rabe C, Sidibe B, Nzunetu G, Konan R, Gnokoro J, Gouesse P, Messou E, Dohoun L, Kamagate S, Yao A, Amon S, Kouame AB, Koua A, Kouame E, Ndri Y, Ba-Gomis O, Daligou M, Ackoundze S, Hawerlander D, Ani A, Dembele F, Kone F, Guehi C, Kanga C, Koule S, Seri J, Oyebi M, Mbakop N, Makaila O, Babatunde C, Babatounde N, Bleoue G, Tchoutedjem M, Kouadio AC, Sena G, Yededji SY, Assi R, Bakayoko A, Mahassadi A, Attia A, Oussou A, Mobio M, Bamba D, Koman M, Horo A, Deschamps N, Chenal H, Sassan-Morokro M, Konate S, Aka K, Aoussi E, Journot V, Nchot C, Karcher S, Chaix ML, Rouzioux C, Sow PS, Perronne C, Girard PM, Menan H, Bissagnene E, Kadio A, Ettiegne-Traore V, Moh-Semde C, Kouame A, Massumbuko JM, Chene G, Dosso M, Domoua SK, N'Dri-Yoman T, Salamon R, Eholie SP, Anglaret X. A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa. N Engl J Med. 2015 Aug 27;373(9):808-22. doi: 10.1056/NEJMoa1507198. Epub 2015 Jul 20.
Background: PubMed 23244049Dye C, Glaziou P, Floyd K, Raviglione M. Prospects for tuberculosis elimination. Annu Rev Public Health. 2013;34:271-86. doi: 10.1146/annurev-publhealth-031912-114431. Epub 2012 Dec 14.
Background: PubMed 21079430Getahun H, Granich R, Sculier D, Gunneberg C, Blanc L, Nunn P, Raviglione M. Implementation of isoniazid preventive therapy for people living with HIV worldwide: barriers and solutions. AIDS. 2010 Nov;24 Suppl 5:S57-65. doi: 10.1097/01.aids.0000391023.03037.1f. No abstract available.
Background: PubMed 22154974Namuwenge PM, Mukonzo JK, Kiwanuka N, Wanyenze R, Byaruhanga R, Bissell K, Zachariah R. Loss to follow up from isoniazid preventive therapy among adults attending HIV voluntary counseling and testing sites in Uganda. Trans R Soc Trop Med Hyg. 2012 Feb;106(2):84-9. doi: 10.1016/j.trstmh.2011.10.015. Epub 2011 Dec 10.
Background: PubMed 21732833Martinson NA, Barnes GL, Moulton LH, Msandiwa R, Hausler H, Ram M, McIntyre JA, Gray GE, Chaisson RE. New regimens to prevent tuberculosis in adults with HIV infection. N Engl J Med. 2011 Jul 7;365(1):11-20. doi: 10.1056/NEJMoa1005136.
Background: PubMed 22150035Sterling TR, Villarino ME, Borisov AS, Shang N, Gordin F, Bliven-Sizemore E, Hackman J, Hamilton CD, Menzies D, Kerrigan A, Weis SE, Weiner M, Wing D, Conde MB, Bozeman L, Horsburgh CR Jr, Chaisson RE; TB Trials Consortium PREVENT TB Study Team. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med. 2011 Dec 8;365(23):2155-66. doi: 10.1056/NEJMoa1104875.
Background: PubMed 26082504Podany AT, Bao Y, Swindells S, Chaisson RE, Andersen JW, Mwelase T, Supparatpinyo K, Mohapi L, Gupta A, Benson CA, Kim P, Fletcher CV; AIDS Clinical Trials Group A5279 Study Team. Efavirenz Pharmacokinetics and Pharmacodynamics in HIV-Infected Persons Receiving Rifapentine and Isoniazid for Tuberculosis Prevention. Clin Infect Dis. 2015 Oct 15;61(8):1322-7. doi: 10.1093/cid/civ464. Epub 2015 Jun 16.
Background: PubMed 24343893Weiner M, Egelund EF, Engle M, Kiser M, Prihoda TJ, Gelfond JA, Mac Kenzie W, Peloquin CA. Pharmacokinetic interaction of rifapentine and raltegravir in healthy volunteers. J Antimicrob Chemother. 2014 Apr;69(4):1079-85. doi: 10.1093/jac/dkt483. Epub 2013 Dec 15.
Background: PubMed 30865794Swindells S, Ramchandani R, Gupta A, Benson CA, Leon-Cruz J, Mwelase N, Jean Juste MA, Lama JR, Valencia J, Omoz-Oarhe A, Supparatpinyo K, Masheto G, Mohapi L, da Silva Escada RO, Mawlana S, Banda P, Severe P, Hakim J, Kanyama C, Langat D, Moran L, Andersen J, Fletcher CV, Nuermberger E, Chaisson RE; BRIEF TB/A5279 Study Team. One Month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis. N Engl J Med. 2019 Mar 14;380(11):1001-1011. doi: 10.1056/NEJMoa1806808.
Background: PubMed 29114781Belknap R, Holland D, Feng PJ, Millet JP, Cayla JA, Martinson NA, Wright A, Chen MP, Moro RN, Scott NA, Arevalo B, Miro JM, Villarino ME, Weiner M, Borisov AS; TB Trials Consortium iAdhere Study Team. Self-administered Versus Directly Observed Once-Weekly Isoniazid and Rifapentine Treatment of Latent Tuberculosis Infection: A Randomized Trial. Ann Intern Med. 2017 Nov 21;167(10):689-697. doi: 10.7326/M17-1150. Epub 2017 Nov 7.
Background: PubMed 28946683Liu X, Blaschke T, Thomas B, De Geest S, Jiang S, Gao Y, Li X, Buono EW, Buchanan S, Zhang Z, Huan S. Usability of a Medication Event Reminder Monitor System (MERM) by Providers and Patients to Improve Adherence in the Management of Tuberculosis. Int J Environ Res Public Health. 2017 Sep 25;14(10):1115. doi: 10.3390/ijerph14101115.
Background: PubMed 25057539Institute of Medicine (US) Committee on Quality of Health Care in America. Crossing the Quality Chasm: A New Health System for the 21st Century. Washington (DC): National Academies Press (US); 2001. Available from http://www.ncbi.nlm.nih.gov/books/NBK222274/
Individual participant dataSharing planned: Yes. Provided upon request

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Adithya Cattamanchi, MD principal investigator

University of California, San Francisco

David W Dowdy, PhD principal investigator

Johns Hopkins Bloomberg School of Public Health

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Participants Who Accepted and Completed 3HP (time frame: Within 16 weeks of treatment initiation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03934931, which also lists 33 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2025.