NCT02120638

Optimization of MDR-TB Treatment Regimen Based on the Molecular Drug Susceptibility Results of Pyrazinamide

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 100 (estimated)
• Sponsor: Huashan Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

Multidrug resistant tuberculosis (MDR-TB) is difficult to treat and raises a great challenge to TB control program. That pyrazinamide can shorten the course of treatment and facilitate bacilli clearance has been proved recently. In 2011, WHO recommended to use pyrazinamide throughout the course of treatment for MDR-TB. However, pyrazinamide susceptibility testing has not been widely used in clinic. And the conventional testing is time-consuming and unreliable. In contrast, the detection of pncA and rpsA mutations with molecular methods can provide rapid results of pyrazinamide susceptibility. The purpose of this study is to evaluate the efficacy of the introduce the molecular testing of pyrazinamide susceptibility in optimizing the MDR-TB treatment regimen.

Detailed description

This is a phase 3, open labeled, prospective cohort study to evaluate the molecular testing of pyrazinamide susceptibility in optimizing the MDR-TB treatment regimen. Approximately 100 participants will be given the molecular detection of pncA and rpsA mutations and divide into to the pyrazinamide sensitive comparator group and the pyrazinamide resistant group based on the susceptibility results. For the pyrazinamide sensitive group, the regimen contains six months of chemotherapy with pyrazinamide, amikacin, levofloxacin, plus prothionamide, followed by six months of pyrazinamide, levofloxacin, clarithromycin, plus prothionamide. For the pyrazinamide resistant group, the regimen contains six months of chemotherapy with isoniazid, amikacin, levofloxacin, plus prothionamide, followed by eighteen months of isoniazid, levofloxacin, clarithromycin, plus prothionamide. The participants will be followed up to 24 months after the start of the treatment. The primary outcome is the sputum culture conversion and the adverse events. Safety evaluations that will be performed are the routine lab tests, blood glucose, hearing , vital signs, ECG, reporting of adverse events, physical examinations and X-rays.

Conditions

• Multidrug Resistant Tuberculosis

Interventions

Type	Name	Description
DRUG	Pyrazinamide containing regimen	Pyrazinamide 33-50kg 1000-1750 mg daily, 51-70kg 1750-2000 daily, \>70kg 2000-2500mg daily Amikacin 600mg daily Levofloxacin 33-70kg 750 mg daily, \>70kg 1000 mg daily Clarithromycin 33-50kg 500 mg daily, \>50kg 1000 mg daily Prothionamide 33-50kg 500 mg daily, 51-70kg 750 daily, \>70kg 1000 mg daily All treatment is taken daily, for a duration of up to 12 months depending on treatment arm.
DRUG	Regimen without Pyrazinamide	Isoniazid 600mg daily Amikacin 600mg daily Levofloxacin 33-70kg 750 mg daily, \>70kg 1000 mg daily Clarithromycin 33-50kg 500 mg daily, \>50kg 1000 mg daily Prothionamide 33-50kg 500 mg daily, 51-70kg 750 daily, \>70kg 1000 mg daily All treatment is taken daily, for a duration of up to 18 months depending on treatment arm.

Timeline

• Start date: 2014-04-01
• Primary completion: 2016-04-01
• Completion: 2016-04-01
• First posted: 2014-04-23
• Last updated: 2014-04-23

Locations

11 sites across 1 country: China