Clinical Trials Logo

Clinical Trial Summary

The purpose of this study is to determine whether one or two four-month regimens of tuberculosis treatment are as effective as a standard six-month regimen for treatment of pulmonary tuberculosis (TB). All three regimens are administered daily, seven days each week, with direct observation of each dose by a health-care worker at least five of the seven days of each week. The standard six-month regimen is two months of isoniazid, rifampin, ethambutol, and pyrazinamide followed by four months of isoniazid and rifampin. The first short regimen is a single substitution of rifapentine for rifampin: two months of isoniazid, rifapentine, ethambutol, and pyrazinamide, followed by two months of isoniazid and rifapentine. The second short regimen is a double substitution of rifapentine for rifampin and moxifloxacin for ethambutol: two months of isoniazid, rifapentine, moxifloxacin, and pyrazinamide, followed by two months of isoniazid, rifapentine, and moxifloxacin. Target enrollment is 2500 participants. Each study participant will remain in the study for 18 months in order to include at least 12 months of evaluation of whether the participant's TB recurs.


Clinical Trial Description

Title: Rifapentine-containing treatment shortening regimens for pulmonary tuberculosis: a randomized, open-label, controlled, phase 3 clinical trial Hypotheses: A) Seventeen (17) week rifapentine-based regimen In previously untreated individuals with active drug-susceptible pulmonary tuberculosis treated with eight weeks of rifapentine (P), isoniazid (H), pyrazinamide (Z) and ethambutol (E) followed by nine weeks of rifapentine plus isoniazid, all given daily throughout, the proportion of participants who experience absence of cure (unfavorable outcome) will not be inferior to that observed in participants who are treated with a standard regimen (eight weeks of rifampin (R), isoniazid, pyrazinamide and ethambutol followed by eighteen weeks of rifampin plus isoniazid), all given daily throughout. B) Seventeen (17) week rifapentine- plus moxifloxacin-containing regimen In previously untreated individuals with active drug-susceptible pulmonary tuberculosis treated with eight weeks of rifapentine, isoniazid, pyrazinamide and moxifloxacin (M), followed by nine weeks of rifapentine, isoniazid, and moxifloxacin, all given daily throughout, the proportion of participants who experience absence of cure (unfavorable outcome) will not be inferior to that observed in participants who are treated with a standard regimen (eight weeks of rifampin, isoniazid, pyrazinamide and ethambutol followed by eighteen weeks of rifampin plus isoniazid), all given daily throughout. Phase: 3 Design: This will be an international, multicenter, randomized, controlled, open-label, 3-arm, phase 3 non-inferiority trial. Population: Patients with newly diagnosed, previously untreated pulmonary tuberculosis. Number of Sites: Multiple international sites, primarily sites of the Tuberculosis Trials Consortium and the AIDS Clinical Trials Group. Study Duration: Duration per participant is approximately 18 months. Description of Agent or Intervention: After written informed consent, participants will be randomly assigned to receive one of the following oral regimens: Regimen 1 (control regimen): 2RHZE/4RH - Eight weeks of daily treatment with rifampin, isoniazid, pyrazinamide, and ethambutol, followed by - Eighteen weeks of daily treatment with rifampin and isoniazid Regimen 2 (investigational regimen): 2PHZE/2PH - Eight weeks of daily treatment with rifapentine, isoniazid, pyrazinamide, and ethambutol, followed by - Nine weeks of daily treatment with rifapentine and isoniazid Regimen 3 (investigational regimen): 2PHZM/2PHM - Eight weeks of daily treatment with rifapentine, isoniazid, pyrazinamide, and moxifloxacin, followed by - Nine weeks of daily treatment with rifapentine, isoniazid, and moxifloxacin Objectives: Primary: - To evaluate the efficacy of a rifapentine-containing regimen to determine whether the single substitution of rifapentine for rifampin makes it possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis - To evaluate the efficacy of a rifapentine-containing regimen that in addition substitutes moxifloxacin for ethambutol and continues moxifloxacin during the continuation phase to determine whether it is possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis Secondary: - To evaluate the safety of the investigational regimens - To evaluate the tolerability of the investigational regimens - To collect and store biospecimens from consenting participants for the purpose of future research on discovery and validation of TB biomarkers - To determine the correlation of mycobacterial and clinical markers with time to culture conversion, culture status at completion of eight weeks of treatment, treatment failure, and relapse. - To conduct a pharmacokinetic/pharmacodynamic (PK/PD) study of the test drugs. The main objectives of the PK/PD study are to characterize study drug PK parameters and to determine relationships between treatment outcomes and PK parameters. - To evaluate the pharmacokinetics of efavirenz-based antiretroviral treatment among patients with TB/HIV co-infection taking efavirenz-based combination antiretroviral therapy and TB treatment with rifapentine Endpoints: Primary Endpoints: - Efficacy: TB disease-free survival at twelve months after study treatment assignment. - Safety: Proportion of participants with grade 3 or higher adverse events during study drug treatment Secondary Endpoints: - TB disease-free survival at eighteen months after study treatment assignment - Time to stable sputum culture conversion (solid and liquid media considered separately) - Speed of decline of sputum viable bacilli by automated liquid MGIT culture days to detection - Proportion of participants who are culture negative at completion of eight weeks of treatment (solid and liquid media considered separately) - Sensitivity analyses assuming all participants classified as 'not assessable' have a favorable outcome - Discontinuation of assigned treatment for a reason other than microbiological ineligibility - Estimated steady state efavirenz PK parameters including mid-dosing interval concentration ;


Study Design


Related Conditions & MeSH terms


NCT number NCT02410772
Study type Interventional
Source Centers for Disease Control and Prevention
Contact
Status Completed
Phase Phase 3
Start date January 25, 2016
Completion date May 2021

See also
  Status Clinical Trial Phase
Recruiting NCT05738681 - Efficacy of N-acetylcysteine to Prevent Anti-tuberculosis Drug-induced Liver Injury: A Randomized Controlled Trial Phase 2/Phase 3
Recruiting NCT05526885 - Tuberculosis Diagnostic Trial of CAD4TB Screening Alone Compared to CAD4TB Screening Combined With a CRP Triage Test, Both Followed by Confirmatory Xpert MTB/RIF Ultra in Communities of Lesotho and South Africa N/A
Completed NCT04369326 - Community Initiated Preventive Therapy for TB N/A
Recruiting NCT04568967 - TB-CAPT EXULTANT - HIV N/A
Completed NCT02337270 - Phase 1 Clinical Trial of the Safety and Immunogenicity of an Adenovirus-based TB Vaccine Administered by Aerosol Phase 1
Not yet recruiting NCT06253715 - Shortened Regimen for Drug-susceptible TB in Children Phase 3
Recruiting NCT04271397 - Immunological Biomarkers in Tuberculosis Management N/A
Withdrawn NCT03639038 - Tuberculosis Diagnosis by Flow Cytometry
Completed NCT03199313 - Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Sutezolid Phase 1
Recruiting NCT04975178 - Efficacy, Safety and Immunogenicity Evaluation of MTBVAC in Newborns in Sub-Saharan Africa Phase 3
Completed NCT04463680 - Rifampin and the Contraceptive Implant Phase 4
Completed NCT03973970 - Assessing the Ability of the T-SPOT®.TB Test (IQ)
Recruiting NCT04230395 - Alcohol Reduction Among People With TB and HIV in India N/A
Completed NCT04874948 - Absorption, Elimination and Safety of 14C-labeled Radioactive BTZ-043, a New Compound in TB Treatment Phase 1
Active, not recruiting NCT02906007 - Evaluating the Pharmacokinetics, Safety, and Tolerability of Bedaquiline in Infants, Children, and Adolescents With Multidrug-Resistant Tuberculosis, Living With or Without HIV Phase 1/Phase 2
Not yet recruiting NCT05917210 - Peer-led Implementation of TB-HIV Education and Adherence Counseling in Uganda N/A
Not yet recruiting NCT05845112 - Start Taking Action For TB Diagnosis
Not yet recruiting NCT06017843 - Impact Evaluation of Use of MATCH AI Predictive Modelling for Identification of Hotspots for TB Active Case Finding N/A
Active, not recruiting NCT02715271 - Study of TB Lesions Obtained in Therapeutical Surgery
Completed NCT02781909 - Potential Efficacy and Safety of Using Adjunctive Ibuprofen for XDR-TB Tuberculosis Phase 2