Rifampicin at High Dose for Difficult-to-Treat Tuberculosis (RIAlta)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04768231|
Recruitment Status : Not yet recruiting
First Posted : February 24, 2021
Last Update Posted : February 24, 2021
|Condition or disease||Intervention/treatment||Phase|
|Tuberculosis||Drug: Rifampin||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||130 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Single intervention group compared with historical controls|
|Masking:||None (Open Label)|
|Official Title:||Safety of Rifampicin at High Dose for the Treatment of Adult Subjects With Complex Drug Susceptible Pulmonary and Extrapulmonary Tuberculosis|
|Estimated Study Start Date :||April 1, 2021|
|Estimated Primary Completion Date :||December 31, 2022|
|Estimated Study Completion Date :||December 31, 2023|
Participants treated with rifampicin at a dose of 35 mg per kilogram of body weight per day, added to the standard doses of isoniazid, pyrazinamide and ethambutol.
The target dose of 35mg/kg will be reached supplementing fixed-dose combination tablets (standard dose) with rifampin-only tablets.
Other Name: Rifampicin
- Safety of rifampicin at 35mg/kg/day [ Time Frame: During the first 8 weeks after treatment start ]Rate of grade 3 or higher adverse events as compared to that in historical controls
- Efficacy of rifampicin at 35mg/kg/day in pulmonary tuberculosis [ Time Frame: At week 8 after treatment start ]Rate of sputum liquid culture conversion (only pulmonary TB participants)
- Tolerability of rifampicin at 35mg/kg/day [ Time Frame: During the first 8 weeks after treatment start ]Rate of adverse events of any grade as compared to that in historical controls
- Bactericidal activity in pulmonary tuberculosis [ Time Frame: During the first 8 weeks after treatment start ]To describe the rate of sputum smear conversion, decline in bacterial load (measured as logCFU/mL), ant time-to-negative smear and culture.
- Pharmacokinetics of rifampicin: Maximum concentration (Cmax) [ Time Frame: After 4 weeks of treatment ]To describe the Camx of rifampicin at 35mg/kg in the population included in the study. A spare-sample strategy sill be used with blood samples taken at 2, 4, and 6 hours after rifampicin administration.
- Pharmacokinetics of rifampicin: Time to maximum concentration (Tmax) [ Time Frame: After 4 weeks of treatment ]To describe the Tmax of rifampicin at 35mg/kg in the population included in the study. A spare-sample strategy sill be used with blood samples taken at 2, 4, and 6 hours after rifampicin administration.
- Pharmacokinetics of rifampicin: Area Under the Curve (AUC) 0-24 [ Time Frame: After 4 weeks of treatment ]To describe the AUC0-24 of rifampicin at 35mg/kg in the population included in the study. A spare-sample strategy sill be used with blood samples taken at 2, 4, and 6 hours after rifampicin administration. The AUC 0-24h will be modelled accodring to the methods described in Magis-Escurrra et al, 2014.
- Pharmacogenetics: analyze the variants in SLCO1B1, ABCB1, UGT1A, and PXR genes [ Time Frame: After 4 weeks of treatment ]Analyze the polymorphisms in SLCO1B1, ABCB1, UGT1A, and PXR genes and their correlation with pharmacokinetic measures from previous outcomes.
- Pharmacodynamics: correlate the AUC0-24/MIC ratio with culture conversion rate [ Time Frame: After 4 weeks of treatment (AUC0-24/MIC) and 8 weeks (culture conversion rate) ]Correlate the pharmacokinetic measure AUC0-24 to the MIC (Minimum Inhibitory Concentration) ratio with the rate of culture conversion of sputum sample at 8 weeks in liquid culture medium.
- AeoNose™ signature during treatment in pulmonary tuberculosis [ Time Frame: Baseline and weeks 1, 2, 4, 6 and 8. ]Evaluate the response to treatment in the exhaled volatile particles signature by means of an electronic nose device: AeoNose™ (The eNose company, the Netherlands)
- Correlation of AeoNose™ with the bactericidal activity in pulmonary tuberculosis [ Time Frame: Baseline and weeks 1, 2, 4, 6 and 8. ]Correlation of the changes in signature by means of an AeoNose™ and the changes in bacillary load during the first 8 weeks of treatment and the culture conversion rate at 8 weeks.
- Health Economics [ Time Frame: During the 6-month standard treatment period. ]To describe tuberculosis associated costs and the incidence of catastrophic costs using the EUSAT-RCS questionnaire based on the WHO handbook for economic studies in tuberculosis in a subgroup of the participants.
- Quality of life [ Time Frame: During the 6-month standard treatment period. ]To describe the changes in quality of life during tuberculosis treatment using the SF-12 questionnaire and the St George's respiratory questionnaire (for pulmonary TB participants) of a subgroup of the included participants
- Extended follow-up: safety [ Time Frame: Up to 12 months after the end of TB treatment. ]After the end of the intervention (8 weeks) data will be collected about severe (grade 3 or higher) or serious adverse events.
- Extended follow-up: cure, treatment failure, relapse [ Time Frame: Up to 12 months after the end of TB treatment. ]After the end of the intervention (8 weeks) data will be collected about clinical outcomes as defined by the WHO (cure, treatment failure, relapse).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04768231
|Contact: Adrián Sánchez-Montalvá, PhD||+34 934893000 ext email@example.com|
|Contact: Juan Espinosa-Pereiro, MD||+34 934893000 ext firstname.lastname@example.org|
|University Medical Center|
|Groningen, Netherlands, 9700 RB|
|Contact: Onno W. Akkerman, MD, PhD +31 643436327 email@example.com|
|Radboud University Medical Center|
|Nijmegen, Netherlands, 6525 EZ|
|Contact: Cecile Magis-Escurra, PhD +31246859770 firstname.lastname@example.org|
|Instituto Nacional de Enfermedades Respiratorias y del Ambiente|
|Asunción, Paraguay, 1424|
|Contact: Arturo Battaglia, MD +595975443343 email@example.com|
|Contact: Gladys Molinas León, MD +595975443343 firstname.lastname@example.org|
|Centro Hospitalario Universitario de Sao Joao|
|Porto, Portugal, 4202-451|
|Contact: Margarida Tavares, MD, MPH +351 963 565873 email@example.com|
|Hospital Universitari Vall d'Hebron. Universitat Autonoma de Barcelona|
|Barcelona, Spain, 08035|
|Principal Investigator:||Adrián Sánchez-Montalvá, PhD||Vall d'Hebron University Hospital|