Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202304463210784 Date of Registration: 24/04/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title 1HP-3HP-AUR1-6-352 - A randomized trial comparing treatment completion of daily Rifapentine & Isoniazid for one month (1HP) to weekly Rifapentine & Isoniazid for 3 months (3HP) in persons living with HIV and in HIV-negative household contacts of recently diagnosed tuberculosis patients, the “One to Three” trial.
Official scientific title A randomized trial comparing treatment completion of daily Rifapentine & Isoniazid for one month (1HP) to weekly Rifapentine & Isoniazid for 3 months (3HP) in persons living with HIV and in HIV-negative household contacts of recently diagnosed tuberculosis patients, the “One to Three” trial.
Brief summary describing the background and objectives of the trial A multicenter, randomized, stratified, open label, phase IV trial among HIV-positive persons (PLHIV) on ART, or HIV-negative household contacts of patients with rifampicin-sensitive pulmonary TB, who do not have evidence of active TB. Participants will be stratified by indication for TPT – HIV seropositive persons or HIV-negative household contact of person with infectious TB – and will receive either one of two TB preventive therapy regimens: Group 1: People living with HIV infection without active TB Arm A: isoniazid (300mg) and rifapentine (600mg) daily for 4 weeks (1HP) Arm B: isoniazid (900mg) and rifapentine (900mg) weekly for 12 weeks (3HP) Group 2: HIV-negative household contacts of newly diagnosed adults with rifampicin-sensitive pulmonary TB. Arm A: isoniazid (300mg) and rifapentine (600mg) daily for 4 weeks (1HP) Arm B: isoniazid (900mg) and rifapentine (900mg) weekly for 12 weeks (3HP) Trial Objective: To compare treatment success (adherence and completion of treatment) and safety of 1HP to 3HP in adolescents and adults who are living with HIV or are HIV-negative household contacts of an adult with confirmed pulmonary TB.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) Dolphin 1 to 3
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied HIV/AIDS,Tuberculosis
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/05/2023
Actual trial start date
Anticipated date of last follow up 31/12/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 1000
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Central randomisation by phone/fax Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group 1HP with ARVs Isoniazid - 1 HP = 300mg Rifapentine - 1 HP = 600mg 28 Days (4 weeks) Rifapentine (Priftin) for oral administration contains 150 mg of the active ingredient rifapentine per tablet. It is a rifamycin antimycobacterial drug indicated in patients 12 years of age and older for the treatment of active pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis in combination with one or more antituberculosis (anti-TB) drugs to which the isolate is susceptible. PRIFTIN is indicated for the treatment of latent tuberculosis infection (LTBI) caused by M.tuberculosis in combination with isoniazid in patients 2 years of age and older at high risk of progression to TB disease. Isoniazid is an antibacterial available as 100 mg and 300 mg tablets for oral administration. It is indicated for: Prophylaxis and treatment of tuberculosis.It is administered with other antituberculosis medicines. 500
Experimental Group 3HP with ARVs Isoniazid - 3 HP = 900mg Rifapentine - 3 HP = 900mg 12 Weeks Rifapentine (Priftin) for oral administration contains 150 mg of the active ingredient rifapentine per tablet. It is a rifamycin antimycobacterial drug indicated in patients 12 years of age and older for the treatment of active pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis in combination with one or more antituberculosis (anti-TB) drugs to which the isolate is susceptible. PRIFTIN is indicated for the treatment of latent tuberculosis infection (LTBI) caused by M.tuberculosis in combination with isoniazid in patients 2 years of age and older at high risk of progression to TB disease. Isoniazid is an antibacterial available as 100 mg and 300 mg tablets for oral administration. It is indicated for: Prophylaxis and treatment of tuberculosis.It is administered with other antituberculosis medicines. 500
Control Group Not Applicable Not Applicable Not Applicable Not Applicable 0 Dose Comparison
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Age ≥ 13 years 2. Weight > 30 kg 3. HIV-seropositive 4. HIV viral load <400 copies/mL, defined as “virally suppressed,” on an EFV or DTG-based ART regimen (see Section 3.6.2) 5. Candidates must meet WHO criteria for receiving TPT 1. Confirmed or suspected TB disease (evidenced by symptoms and/or clinical exam findings and/or chest radiographic findings suggestive of TB, positive mycobacterial culture or molecular TB testing or currently on TB treatment for active TB disease) 2. Likely to move from the study area during the study period 3. Known recent exposure to a TB case with resistance to isoniazid or rifampicin. 4. Previous treatment for active or latent TB for more than 30 days within the past 2 years 5. On nevirapine, etravirine, rilpivirine, PI-based, or raltegravir-containing ART regimens 6. Known sensitivity or intolerance to isoniazid or rifamycins 7. Suspected acute hepatitis or known chronic or unstable liver disease^ 8. ALT > 3 times the upper limit of normal (ULN) 9. Total bilirubin > 2.5 times the ULN T 10. Pregnancy or breastfeeding Females of childbearing potential who are unable or unwilling to use two forms of contraception** 11. On prohibited medications 80 and over: 80+ Year,Adolescent: 13 Year(s)-17 Year(s),Adult: 18 Year(s)-44 Year(s),Aged: 65 Year(s)-79 Year(s),Middle Aged: 45 Year(s)-64 Year(s) 13 Year(s) 105 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 15/09/2022 University of the Witwatersrand Human Research Ethics Committee Medical
Ethics Committee Address
Street address City Postal code Country
31 Princess of Wales Terrace, Parktown Johannesburg 2193 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome (1) Successful completion of TPT with >90% adherence documented by self-report, pill count, and EMD reporting. (2) Safety of treatment regimens, defined as occurrence of Grade 2 or higher targeted safety events and discontinuation of study medications because of side effects. Targeted safety events are hypersensitivity syndrome, rash, seizure, peripheral neuropathy, hepatotoxicity, nausea and vomiting, and drug-related fever. 1HP at Days 28 and 42. 3HP at Days 28, 56, 84, 112, 126.
Secondary Outcome (1) Incremental cost-effectiveness of 1HP and 3HP (compared to each other, 6H, and no treatment) using a societal perspective. Calculated at various time points throughout the study
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
The Aurum Institute Gavin J Churchyard Legacy Centre 201 Jade Square Centre, Cnr OR Tambo and Margaretha Prinsloo Streets Klerksdorp 2571 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
UNITAID Global Health Campus, Chemin du Pommier 40, 5th floor, 1218 Grand-Saconnex Geneva Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor The Aurum Institute NPC 29 Queens Road, Parktown Johannesburg 2193 South Africa Organization
COLLABORATORS
Name Street address City Postal code Country
The Aurum Institute 29 Queens Avenue Johannesburg 2193 South Africa
Johns Hopkins University Baltimore Maryland United States of America
KNCV Fund Maanweg 174 2516 AB The Hague Netherlands
The Aurum Institute Mozambique 396 Amilcar Cabral Avenue, Bairro Central Maputo Mozambique
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator James Craig Innes cinnes@auruminstitute.org +27871351616 201 Jade Square, cnr OR Tambo and Margaretha Prinsloo streets
City Postal code Country Position/Affiliation
Klerksdorp 2571 South Africa Principal Investigator
Role Name Email Phone Street address
Public Enquiries Jayajothi Moodley jmoodley@auruminstitute.org +27826593766 29 Queens Road, Parktown
City Postal code Country Position/Affiliation
Johannesburg 2193 South Africa Programme Manager
Role Name Email Phone Street address
Scientific Enquiries Violet Chihota vchihota@auruminstitute.org +27105901432 29 Queens Road, Parktown
City Postal code Country Position/Affiliation
Johannesburg 2193 South Africa Chief Specialist Scientist
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes De-identified participant data will be available but accessed upon request and approval. In addition, third parties may obtain study data access upon request and permission of the Steering Group Clinical Study Report Data requests can be submitted starting 1 year after article publication, and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis. Request Access via Primary Author. Controlled Access
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information