A Study of Ultrashort PRS Regimen V in the Treatment of MDR-TB

Study Overview
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Brief Summary
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This is an exploratory, prospective, randomized, active control, and open label clinical trial to evaluate the efficacy and safety of 6-9 months treatment with the ultrashort PRS Regimen V.

Detailed Description
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Shortening the course of treatment based on effective therapy can significantly improve patient compliance and reduce the public health burden.Research on optimal drug combination regimens to further shorten the duration and improve the efficacy of multidrug-resistant tuberculosis treatment is an important research direction.The PRS (parabolic response surface, FSC.II) system is an enhanced use of FSC to better identify and optimize optimal drug combinations.In preliminary studies, it was determined that PRS Regimens V （bedaquiline, delamanid, clofazimine, pyrazinamide）was superior to other regimens and would be a promising combination for XDR-TB because it does not contain fluoroquinolones or aminoglycosides. Preliminary trials have demonstrated that this regimen (PRS Regimens IV) can significantly reduce the duration of treatment required for MDR-TB and achieve a relapse-free cure. Therefore, the investigators conducted an exploratory, prospective, randomized, positive-controlled, open, multicenter clinical study of this new regimen to observe the efficacy, safety, and recent relapse rate of the new regimen in the treatment of multidrug-resistant tuberculosis.

Official Title
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A Study of Ultrashort PRS Regimen V in the Treatment of MDR-TB

Conditions
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MDR-TB

Intervention / Treatment
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* Drug: PRS Regimen V
* Drug: MDR-TB Treatment Regimen(WHO)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Untreated newly diagnosed patients with rifampicin resistant (RR) or multidrug resistant (MDR)-TB. Newly treated patients: at least twice confirmed by molecular biology or phenotypic drug susceptibility test to have RR- or MDR-TB; Retreated patients: confirmed once by molecular biology or phenotypic drug susceptibility test to have RR- or MDR-TB. Age between 18 and 65. No abnormality on EKG. Able to understand and sign informed consent form. Exclusion Criteria: Presence of extrapulmonary TB (including tuberculous pleurisy); History of allergic reaction to any of the drugs used in the study; Presence of any of the following conditions that can lead to prolonged QT: During screening process, ECG shows QT or QTc interval ≥ 450 ms (permit one non-prescheduled retest within the screening period to re-evaluate the testees' qualification); Pathological Q waves (any Q wave duration of > 40 ms or depth > 0.4-0.5 mV); Evidence of ventricular pre-excitation (such as Wolff-Parkinson-White Syndrome); EKG shows evidence of complete or clinically significant incomplete left or right bundle branch block; Evidence of 2nd or 3rd degree heart block; Intraventricular conduction delay, QRS durations > 120 ms; Slow heart rate, defined as sinus heart rate < 50 bpm; Having personal or family history of long QT syndrome; Having heart disease, symptomatic or asymptomatic arrhythmia, excluding sinus arrhythmia; Fainting (i.e., cardiogenic fainting, not including vasovagal syncope or seizure) Having risk factors for Torsade de pointes ventricular tachycardia (e.g. heart failure, hypokalemia, hypomagnesemia) Pregnancy or liver, kidney, metabolic, autoimmunity, neurological, psychological or endocrine disease, blood system disease, malignant cancer, long-term users of immunosuppressant drugs. Alcoholism Any patients, based on the judgement of the study medical researchers who are not suitable to participate in the trial or unlikely to complete the trial. Participating in another clinical trial at the same time. History of non-compliance in other clinical trials.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A<br>Treatment according to WHO MDR-TB treatment guidelines (2019). | Drug: MDR-TB Treatment Regimen(WHO)<br>* Treatment according to WHO MDR-TB treatment guidelines (2019)<br>* Other names: WHO Regimen;|
| Experimental: Group B(PRS Regimen V)<br>bedaquiline, delamanid, clofazimine, pyrazinamide | Drug: PRS Regimen V<br>* PRS Regimen V(bedaquiline, delamanid, clofazimine, pyrazinamide)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| patient cure rate | Assessment of cure rate : Cure. Treatment completion. Treatment failure. Death. Loss. Inconclusive. Treatment success. | Through study completion, an average of 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early bactericidal activity (EBA) | Collect patient sputum between 16:00 to 8:00 the next morning before taking drugs prior to treatment initiation (Day 0; D0) and on Day 2 (D2), Day 7 (D7), and Day 14 (D14) after the start of treatment | treatment initiation (Day 0; D0) and on Day 2 (D2), Day 7 (D7), and Day 14 (D14) after the start of treatment | 
| Time to culture positivity | culture using MGIT 960 and observe the time to detection of positive growth. | Through study completion, an average of 18 months | 
| Sputum conversion rate | ompare patient sputum conversion rate between the two groups at one month and two months. | Through study completion, an average of 18 months | 
| Radiology changes | Significant absorption is defined as lesion absorption ≥ ½. Absorption is defined as lesion absorption ≤ ½. No change if the original lesion has no clear change. Worsened if the original lesion is enlarged or has spread. Closure if the original cavity is enclosed or enclosed by blockage. Shrinkage if diameter of the original cavity decreased by ≥1/2. No change if diameter of the original cavity decreases by <1/2. Enlarged if diameter of the original cavity increases by >1/2. | Through study completion, an average of 18 months | 
| Relapse rate one and two years after treatment completion. | follow up at 3, 6, 12, 18, and 24 months after treatment completion | At 3, 6, 12, 18, and 24 months | 
| Time to Cure by Primary Endpoint criteria | Time to Cure by Primary Endpoint criteria | 6-9 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDR-TB, Delamanid, bedaquiline