Optimizing(O) RIfapentine-based(RI) Regimen and shortENing(EN) the Treatment of Drug-sensitive Tuberculosis(T)

NCT05401071 | Recruiting Phase 2 DMC

• 1 other identifier: ORIENT
• Study Type: interventional
• Target: 2,442
• Locations: 1 country
• Sites: 6

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.

Conditions

Tuberculosis, Pulmonary

Keywords

rifapentine; shorter treatment; pulmonary tuberculosis

Outcome Measures

Primary Outcomes (1)

• Treatment success rate of the short regimen during drug treatment and follow-up.

  To compare the treatment success rate without relapse between the short regimen with rifapentine 10mg/kg, the short regimen with rifapentine 15mg/kg, the short regimen with rifapentine 20mg/kg and the WHO standardized regimen group.

  108 weeks after randomization

Secondary Outcomes (3)

• The frequency of grade 3 or greater adverse events among patients Over the 108 Week Treatment and Follow-up Period.

  up to 108 weeks

• Relapse rate during follow-up.

  82-91 weeks after the end of drug treatment.

• the percentage of participants found to be culture-negative at the end of intensive phase and the end of treatment phase

  8 weeks, 17 weeks and 26 weeks after randomization

Study Arms (4)

Short Regimen with Rifapentine 10mg/kg

EXPERIMENTAL

Intervention: Short Regimen with Rifapentine 10mg/kg consists of two periods of 17- 26 weeks. The first is an intensive phase of 8 weeks, and included rifapentine, isoniazid, pyrazinamide, and moxifloxacin. This is followed by a continuation phase of 9 weeks with the following agents: rifapentine, isoniazid and moxifloxacin (extended up a maximum of 18 weeks if no smear conversion at the end of 8 weeks or the tuberculosis cavity is not closed at the end of 17 weeks).

Other: Short Regimen with Rifapentine 10mg/kg

Short Regimen with Rifapentine 15mg/kg

EXPERIMENTAL

Intervention: Short Regimen with Rifapentine 15mg/kg consists of two periods of 17- 26 weeks. The first is an intensive phase of 8 weeks, and included rifapentine, isoniazid, pyrazinamide, and moxifloxacin. This is followed by a continuation phase of 9 weeks with the following agents: rifapentine, isoniazid and moxifloxacin (extended up a maximum of 18 weeks if no smear conversion at the end of 8 weeks or the tuberculosis cavity is not closed at the end of 17 weeks).

Other: Short Regimen with Rifapentine 15mg/kg

Standardized Regimen

ACTIVE COMPARATOR

Intervention：World Health Organization (WHO) Standardized Regimen group consists of 26 weeks with two phases of treatment. The first is an intensive phase of 8 weeks, and included rifampicin, isoniazid, pyrazinamide, and ethambutol. This is followed by a continuation phase of 18 weeks with the following agents: rifampicin and isoniazid.

Combination Product: Standardized Regimen

Short Regimen with Rifapentine 20mg/kg

EXPERIMENTAL

Intervention: Short Regimen with Rifapentine 20mg/kg consists of two periods of 17- 26 weeks. The first is an intensive phase of 8 weeks, and included rifapentine, isoniazid, pyrazinamide, and moxifloxacin. This is followed by a continuation phase of 9 weeks with the following agents: rifapentine, isoniazid and moxifloxacin (extended up a maximum of 18 weeks if no smear conversion at the end of 8 weeks or the tuberculosis cavity is not closed at the end of 17 weeks).

Other: Short Regimen with Rifapentine 20mg/kg

Interventions

Short Regimen with Rifapentine 10mg/kg OTHER

rifapentine 10mg/kg daily; isoniazid 300mg daily; pyrazinamide ≤50kg 1000mg daily, 50-71kg 1200mg daily, \>71kg 1000mg daily; moxifloxacin 400mg daily. All treatment is taken orally.

Short Regimen with Rifapentine 10mg/kg

Standardized Regimen COMBINATION_PRODUCT

During the intensive phase, rifampicin ≤55kg 450mg daily, 55-71kg 600mg daily, \>71kg 750mg daily; isoniazid ≤55kg 225mg daily, 55-71kg 300mg daily, \>71kg 375mg daily; pyrazinamide ≤55kg 900mg daily, 55-71kg 1200mg daily, \>71kg 1600mg daily; ethambutol ≤55kg 825mg daily, 55-71kg 1100mg daily, \>71kg 1375mg daily; All treatment is taken orally. During the continuation phase, rifampicin ≤50kg 450mg daily, \>50kg 600mg daily; isoniazid 300mg daily; All treatment is taken orally.

Standardized Regimen

Short Regimen with Rifapentine 15mg/kg OTHER

rifapentine 15mg/kg daily; isoniazid 300mg daily; pyrazinamide ≤50kg 1000mg daily, 50-71kg 1200mg daily, \>71kg 1000mg daily; moxifloxacin 400mg daily. All treatment is taken orally.

Short Regimen with Rifapentine 15mg/kg

Short Regimen with Rifapentine 20mg/kg OTHER

rifapentine 20mg/kg daily; isoniazid 300mg daily; pyrazinamide ≤50kg 1000mg daily, 50-71kg 1200mg daily, \>71kg 1000mg daily; moxifloxacin 400mg daily. All treatment is taken orally.

Short Regimen with Rifapentine 20mg/kg

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Huashan Hospital: lead

Study Sites (6)

Guiyang Public Health Clinical Center

Guiyang, Guizhou, China

NOT YET RECRUITING

People's Hospital of Qiandongnan

Kaili, Guizhou, China

NOT YET RECRUITING

The Third People's Hospital of Liupanshui

Liupanshui, Guizhou, China

NOT YET RECRUITING

Affiliated Hospital of Zunyi Medical University

Zunyi, Guizhou, China

NOT YET RECRUITING

Department of Infectious Disease, Huashan Hospital

Shanghai, Shanghai Municipality, 200040, China

RECRUITING

People's Hospital of Zhuji, Zhejiang Province

Zhuji, Zhejiang, 311899, China

NOT YET RECRUITING

Related Publications (1)

• Feng Z, Miao Y, Peng Y, Sun F, Zhang Y, Li R, Ge S, Chen X, Song L, Li Y, Wang X, Zhang W. Optimizing (O) rifapentine-based (RI) regimen and shortening (EN) the treatment of drug-susceptible tuberculosis (T) (ORIENT) using an adaptive seamless design: study protocol of a multicenter randomized controlled trial. BMC Infect Dis. 2023 May 8;23(1):300. doi: 10.1186/s12879-023-08264-2.

  PMID: 37158831 DERIVED

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

rifapentine

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Wenhong Zhang, PhD.

  Huashan Hospital of Fudan University，Shanghai，China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Feng Sun, Dr.

CONTACT

(086)15921403893; aaronsf1125@126.com

Yang Li, Dr.

CONTACT

(086)18817583793; y_li11@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Division of Infectious Diseases

Study Record Dates

• First Submitted: February 27, 2022
• First Posted: June 2, 2022
• Study Start: January 13, 2023
• Primary Completion: October 1, 2024
• Study Completion (Estimated): November 1, 2027
• Last Updated: December 11, 2023

Record last verified: 2023-12

Locations

CN (6)