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

Shanghai Pulmonary Hospital, Shanghai, China

Status and phase: Completed; Phase 4

Conditions: MDR-TB

Treatments: Drug: PRS Regimen V; Drug: MDR-TB Treatment Regimen(WHO)

Study type: Interventional

Funder types: Other

Identifiers

NCT05278988

K21-024

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 60 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Untreated newly diagnosed patients with rifampicin resistant (RR) or multidrug resistant (MDR)-TB.
2. 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.
3. Age between 18 and 65.
4. No abnormality on EKG.
5. Able to understand and sign informed consent form.

Exclusion criteria

1. Presence of extrapulmonary TB (including tuberculous pleurisy);

2. History of allergic reaction to any of the drugs used in the study;

3. Presence of any of the following conditions that can lead to prolonged QT:

   1. 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);
   2. Pathological Q waves (any Q wave duration of > 40 ms or depth > 0.4-0.5 mV);
   3. Evidence of ventricular pre-excitation (such as Wolff-Parkinson-White Syndrome);
   4. EKG shows evidence of complete or clinically significant incomplete left or right bundle branch block;
   5. Evidence of 2nd or 3rd degree heart block;
   6. Intraventricular conduction delay, QRS durations > 120 ms;
   7. Slow heart rate, defined as sinus heart rate < 50 bpm;
   8. Having personal or family history of long QT syndrome;
   9. Having heart disease, symptomatic or asymptomatic arrhythmia, excluding sinus arrhythmia;
   10. Fainting (i.e., cardiogenic fainting, not including vasovagal syncope or seizure)
   11. Having risk factors for Torsade de pointes ventricular tachycardia (e.g. heart failure, hypokalemia, hypomagnesemia)

4. Pregnancy or liver, kidney, metabolic, autoimmunity, neurological, psychological or endocrine disease, blood system disease, malignant cancer, long-term users of immunosuppressant drugs.

5. Alcoholism

6. 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.

7. Participating in another clinical trial at the same time.

8. History of non-compliance in other clinical trials.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Group A

Active Comparator group

Description:

Treatment according to WHO MDR-TB treatment guidelines (2019).

Treatment:

Drug: MDR-TB Treatment Regimen(WHO)

Group B(PRS Regimen V)

Experimental group

Description:

bedaquiline, delamanid, clofazimine, pyrazinamide

Treatment:

Drug: PRS Regimen V