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

December 8, 2023 updated by: Wen-hong Zhang, Huashan Hospital

Efficacy and Safety of Short-course Treatment for Drug-sensitive Tuberculosis in China

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

2442

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Guizhou
      • Guiyang, Guizhou, China
        • Not yet recruiting
        • Guiyang Public Health Clinical Center
        • Contact:
          • Cui Cai
      • Kaili, Guizhou, China
        • Not yet recruiting
        • People's Hospital of Qiandongnan
        • Contact:
          • Jing Wang
      • Liupanshui, Guizhou, China
        • Not yet recruiting
        • The Third People's Hospital of Liupanshui
        • Contact:
          • Chunlong Zhang
      • Zunyi, Guizhou, China
        • Not yet recruiting
        • Affiliated Hospital of Zunyi Medical University
        • Contact:
          • Jianyong Zhang
    • Shanghai
      • Shanghai, Shanghai, China, 200040
        • Recruiting
        • Department of Infectious Disease, Huashan Hospital
        • Contact:
    • Zhejiang
      • Zhuji, Zhejiang, China, 311899
        • Not yet recruiting
        • People's Hospital of Zhuji, Zhejiang Province
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Short Regimen with Rifapentine 10mg/kg
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
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.
Experimental: Short Regimen with Rifapentine 15mg/kg
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
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.
Active Comparator: Standardized Regimen
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

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.
Experimental: Short Regimen with Rifapentine 20mg/kg
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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment success rate of the short regimen during drug treatment and follow-up.
Time Frame: 108 weeks after randomization
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
The frequency of grade 3 or greater adverse events among patients Over the 108 Week Treatment and Follow-up Period.
Time Frame: up to 108 weeks
To compare the proportion of patients who experience grade 3 or greater adverse events 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.
up to 108 weeks
Relapse rate during follow-up.
Time Frame: 82-91 weeks after the end of drug treatment.
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.
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
Time Frame: 8 weeks, 17 weeks and 26 weeks after randomization
To compare the percentage of participants found to be culture-negative at the end of intensive phase and the end of treatment phase 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.
8 weeks, 17 weeks and 26 weeks after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Huashan Hospital

Investigators

  • Principal Investigator: Wenhong Zhang, PhD., Huashan Hospital of Fudan University，Shanghai，China

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 13, 2023

Primary Completion (Estimated)

October 1, 2024

Study Completion (Estimated)

November 1, 2027

Study Registration Dates

First Submitted

February 27, 2022

First Submitted That Met QC Criteria

May 28, 2022

First Posted (Actual)

June 2, 2022

Study Record Updates

Last Update Posted (Estimated)

December 11, 2023

Last Update Submitted That Met QC Criteria

December 8, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ORIENT

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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