Clinical trial NCT05401071: Optimizing(O) RIfapentine-based(RI) Regimen and shortENing(EN) the Treatment of Drug-sensitive Tuberculosis(T)
Official title: Efficacy and Safety of Short-course Treatment for Drug-sensitive Tuberculosis in China
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Tuberculosis, Pulmonary
Keywords: rifapentine
shorter treatment
pulmonary tuberculosis
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2022-06-02
Enrollment: 2442
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Tuberculosis (TB) remains the most important infectious disease in the world. A major barrier to tuberculosis control is poor adherence to long-term and complex treatment regimens.

This is a multicenter prospective, non-inferiority randomized controlled study. The purpose of our study is a) to evaluate the tolerability, efficacy and pharmacokinetics/pharmacodynamics (PK/PD) of the high-dose rifapentine, b) to evaluate whether the high-dose rifapentine-containing regimen has the potential to treat the rifampicin-sensitive pulmonary tuberculosis and shorten the course of treatment to 17 weeks. This study is of great significance for shortening the course of treatment, reducing the adverse reactions and economic burden of patients' treatment in rifampicin-sensitive tuberculosis patient.

Detailed description: Tuberculosis (TB) remains the most important infectious disease in the world. A major barrier to tuberculosis control is poor adherence to long-term and complex treatment regimens. Incomplete TB treatment can lead to increased morbidity and mortality, prolonged infectivity and transmission, and the development of drug resistance. The development of new therapeutic strategies with stronger bactericidal activity could lead to shorter and better-tolerated regimens, thereby increasing cure rates, lowering costs, potentially reducing transmission and preventing the emergence of multidrug-resistant tuberculosis (MDR-TB).

This trial is a multicenter prospective, non-inferiority randomized controlled study. Rifampicin-sensitive pulmonary tuberculosis patients will be included in our study. Stage 1 of the study is designed to evaluate the tolerability, efficacy and PK/PD of the high-dose rifapentine in order to select two doses to carry forward into study Stage 2. Study Stage 2 will provide pivotal confirmation of efficacy, safety, and tolerability of the selected rifapentine doses in patients with rifampicin-sensitive pulmonary tuberculosis.

Eligibility criteria: Inclusion Criteria:

* Age between 18 to 60 years;
* Weight between 40 to 80 kg;
* Individuals with smear-positive pulmonary tuberculosis and sensitive to rifampicin ;
* Willing to provide signed informed consent, or parental consent and participant assent.
* If you are a non-menopausal woman, agree to use or have used effective contraception during treatment.

Exclusion Criteria:

* Combined extrapulmonary tuberculosis;
* Patients with extensive lesion (extent of disease greater than 50% or cavity size greater than 4cm) ;
* Individuals will be excluded from enrollment if, at the time of enrollment, their M. tuberculosis isolate is already known to be resistant to any one or more of the following: rifampin, isoniazid, pyrazinamide, ethambutol, or fluoroquinolones;
* Alcohol abuse#drinking more than 64g of ethanol a day for male, 42g for female#;
* Hemoglobin is less than 70g/L or platelet is less than 100\*10\^9/L;
* Patients with impaired liver function (hepatic encephalopathy, ascites; total bilirubin is higher than the upper limit of normal; Alanine aminotransferase or aspartate aminotransferase is higher than the upper limit of normal);
* Blood creatinine is more than 1.5 times the upper limit of normal;
* More than five days of systemic treatment with any one or more of the following drugs within 6 months preceding initiation of study drugs: isoniazid, rifampin, rifabutin, rifapentine, ethambutol, pyrazinamide, kanamycin, amikacin, streptomycin, capreomycin, moxifloxacin, levofloxacin, gatifloxacin, ofloxacin, ciprofloxacin, other fluoroquinolones, ethionamide, prothionamide, cycloserine, terizidone, para-aminosalicylic acid, linezolid, clofazimine, delamanid or bedaquiline;
* Known history of prolonged QT syndrome;
* Current or planned use within six months following enrollment of one or more of the following medications: HIV protease inhibitors, HIV integrase inhibitors, HIV entry and fusion inhibitors, HIV non-nucleoside reverse transcriptase inhibitors other than efavirenz; quinidine, procainamide, amiodarone, sotalol, disopyramide, ziprasidone, or terfenadine;
* Known allergy or intolerance to any of the study medications;
* AIDS patients;
* Pregnant or breast-feeding.

Primary outcomes:
measure: Treatment success rate of the short regimen during drug treatment and follow-up.
timeFrame: 108 weeks after randomization
Secondary outcomes:
measure: The frequency of grade 3 or greater adverse events among patients Over the 108 Week Treatment and Follow-up Period.
timeFrame: up to 108 weeks
measure: Relapse rate during follow-up.
timeFrame: 82-91 weeks after the end of drug treatment.
measure: the percentage of participants found to be culture-negative at the end of intensive phase and the end of treatment phase
timeFrame: 8 weeks, 17 weeks and 26 weeks after randomization
Other outcomes:
Locations:
city: Guiyang
country: China
facility: Guiyang Public Health Clinical Center
state: Guizhou
city: Kaili
country: China
facility: People's Hospital of Qiandongnan
state: Guizhou
city: Liupanshui
country: China
facility: The Third People's Hospital of Liupanshui
state: Guizhou
city: Zunyi
country: China
facility: Affiliated Hospital of Zunyi Medical University
state: Guizhou
city: Shanghai
country: China
facility: Department of Infectious Disease, Huashan Hospital
state: Shanghai
city: Zhuji
country: China
facility: People's Hospital of Zhuji, Zhejiang Province
state: Zhejiang
Study officials:
affiliation: Huashan Hospital of Fudan University，Shanghai，China
name: Wenhong Zhang, PhD.
role: PRINCIPAL_INVESTIGATOR
References: