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

Primary Purpose

Tuberculosis, Pulmonary

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Short Regimen with Rifapentine 10mg/kg
Standardized Regimen
Short Regimen with Rifapentine 15mg/kg
Short Regimen with Rifapentine 20mg/kg
Sponsored by
Huashan Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tuberculosis, Pulmonary focused on measuring rifapentine, shorter treatment, pulmonary tuberculosis

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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*10^6/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.

Sites / Locations

  • Guiyang Public Health Clinical Center
  • People's Hospital of Qiandongnan
  • The Third People's Hospital of Liupanshui
  • Affiliated Hospital of Zunyi Medical University
  • Department of Infectious Disease, Huashan HospitalRecruiting
  • People's Hospital of Zhuji, Zhejiang Province

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Active Comparator

Experimental

Arm Label

Short Regimen with Rifapentine 10mg/kg

Short Regimen with Rifapentine 15mg/kg

Standardized Regimen

Short Regimen with Rifapentine 20mg/kg

Arm Description

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).

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).

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.

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

The frequency of grade 3 or greater adverse events among patients Over the 108 Week Treatment and Follow-up Period.
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.
Relapse rate during 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.
the percentage of participants found to be culture-negative at the end of intensive phase and the end of treatment phase
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.

Full Information

First Posted
February 27, 2022
Last Updated
March 27, 2023
Sponsor
Huashan Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05401071
Brief Title
Optimizing(O) RIfapentine-based(RI) Regimen and shortENing(EN) the Treatment of Drug-sensitive Tuberculosis(T)
Acronym
ORIENT
Official Title
Efficacy and Safety of Short-course Treatment for Drug-sensitive Tuberculosis in China
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 13, 2023 (Actual)
Primary Completion Date
October 1, 2023 (Anticipated)
Study Completion Date
November 1, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Huashan Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis, Pulmonary
Keywords
rifapentine, shorter treatment, pulmonary tuberculosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
2442 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Short Regimen with Rifapentine 10mg/kg
Arm Type
Experimental
Arm Description
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).
Arm Title
Short Regimen with Rifapentine 15mg/kg
Arm Type
Experimental
Arm Description
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).
Arm Title
Standardized Regimen
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Short Regimen with Rifapentine 20mg/kg
Arm Type
Experimental
Arm Description
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).
Intervention Type
Other
Intervention Name(s)
Short Regimen with Rifapentine 10mg/kg
Intervention Description
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.
Intervention Type
Combination Product
Intervention Name(s)
Standardized Regimen
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Short Regimen with Rifapentine 15mg/kg
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Short Regimen with Rifapentine 20mg/kg
Intervention Description
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.
Primary Outcome Measure Information:
Title
Treatment success rate of the short regimen during drug treatment and follow-up.
Description
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.
Time Frame
108 weeks after randomization
Secondary Outcome Measure Information:
Title
The frequency of grade 3 or greater adverse events among patients Over the 108 Week Treatment and Follow-up Period.
Description
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.
Time Frame
up to 108 weeks
Title
Relapse rate during follow-up.
Description
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.
Time Frame
82-91 weeks after the end of drug treatment.
Title
the percentage of participants found to be culture-negative at the end of intensive phase and the end of treatment phase
Description
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.
Time Frame
8 weeks, 17 weeks and 26 weeks after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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*10^6/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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Feng Sun, Dr.
Phone
(086)15921403893
Ext
8123
Email
aaronsf1125@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yang Li, Dr.
Phone
(086)18817583793
Ext
8123
Email
y_li11@fudan.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wenhong Zhang, PhD.
Organizational Affiliation
Huashan Hospital of Fudan University，Shanghai，China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Guiyang Public Health Clinical Center
City
Guiyang
State/Province
Guizhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cui Cai
Facility Name
People's Hospital of Qiandongnan
City
Kaili
State/Province
Guizhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jing Wang
Facility Name
The Third People's Hospital of Liupanshui
City
Liupanshui
State/Province
Guizhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chunlong Zhang
Facility Name
Affiliated Hospital of Zunyi Medical University
City
Zunyi
State/Province
Guizhou
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jianyong Zhang
Facility Name
Department of Infectious Disease, Huashan Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200040
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hongyu Wang
Phone
17717366509
Email
rubywang961208@gmail.com
Facility Name
People's Hospital of Zhuji, Zhejiang Province
City
Zhuji
State/Province
Zhejiang
ZIP/Postal Code
311899
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heqing Huang
Phone
13858516315
Email
zjganran@163.com

12. IPD Sharing Statement

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

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