Effectiveness of a Simplified Short Regimen for Multidrug Resistant Tuberculosis in Uzbekistan

NCT ID: NCT02496572

Last Updated: 2015-07-14

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 110 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2016-04-30

Brief Summary

Multidrug resistant tuberculosis (MDR TB) is a growing problem and few people have access to adequate diagnosis and treatment. The current recommended treatment regimen for MDR TB has a minimum of 20 months duration with high toxicity. Scale up of MDR TB treatment is associated with high default rates, and experience in the Medecins Sans Frontieres (MSF) programme in Uzbekistan shows that the current standard treatment greatly limits the ability to scale up to meet the high rates of MDR TB in the region.

Evidence from Bangladesh in 2010 showed that a 9-month short-course regimen could achieve a relapse-free cure rate of 88%. Several countries in West Africa started implementing similar regimens with similar outcomes. Evidence of effectiveness of this shortened regimen among regions with high second line drug use and resistance is still limited.

The investigators propose an observational study under programmatic conditions to evaluate the effectiveness of a shortened course MDR TB regimen in the high MDR/extensively drug resistant (XDR) TB prevalence and high second-line drug resistance setting of Karakalpakstan, Uzbekistan.

Detailed Description

A prospective observational study has been designed. The study regimen is composed of an intensive phase of at least 4 months duration of Pyrazinamide (Z) + Ethambutol (E) + Isoniazid (H) + Moxifloxacin (Mfx) + Capreomycin (or Kanamycin/Amikacin) (Cm/Km/Am) + Prothionamide (Pto) + Clofazimine (Cfz) and a continuation phase of oral drugs Z-E-Mfx-Pto-Cfz. Patients will be followed up until the end of treatment and during 12 months after treatment completion in order to evaluate the rate of relapse.

Data will be recorded in patient's clinical files and electronic databases and analyzed with Stata 11.0.

This study is a result of ongoing collaboration of MSF with the Ministry of Health in Uzbekistan; results will be shared with the national health authorities, World Health Organization and the rest of the scientific community and aim to influence and improve treatment and care of patients with MDR TB.

Conditions

Multidrug Resistant Tuberculosis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Short-course MDR-TB regimen patients

Short course MDR-TB treatment regimen. New presumptively diagnosed MDR TB patients (adults and children) with Xpert® MTB/RIF or Hain MTBDR, or confirmed with Hain MTBDR plus on positive cultures if initial molecular tests negative or confirmed from MGIT culture/DST if initial molecular tests negative;

Children (<14 years old) suspected of MDR TB without bacteriological confirmation but documented as a close contact of a confirmed MDR TB patient

Short course MDR-TB treatment regimen

Intervention Type: DRUG

Intensive phase:

Pyrazinamide (Z) + Ethambutol (E) + Isoniazid (H) + Moxifloxacin (Mfx) + Capreomycin (Cm) + Prothionamide (Pto) + Clofazimine (Cfz) for at least 4 months and until one negative culture is documented with a maximum of 6 months duration.

Continuation phase:

Continuation phase of Pyrazinamide (Z) + Ethambutol (E) + Moxifloxacin (Mfx) + Prothionamide (Pto) + Clofazimine (Cfz) for fixed 5 months duration.

Interventions

Short course MDR-TB treatment regimen

Intensive phase:

Pyrazinamide (Z) + Ethambutol (E) + Isoniazid (H) + Moxifloxacin (Mfx) + Capreomycin (Cm) + Prothionamide (Pto) + Clofazimine (Cfz) for at least 4 months and until one negative culture is documented with a maximum of 6 months duration.

Continuation phase:

Continuation phase of Pyrazinamide (Z) + Ethambutol (E) + Moxifloxacin (Mfx) + Prothionamide (Pto) + Clofazimine (Cfz) for fixed 5 months duration.

Intervention Type: DRUG

Other Intervention Names

Bangladesh protocol; Shortened course MDR-TB treatment; 9-month MDR-TB regimen

Eligibility Criteria

Inclusion Criteria

• New presumptively diagnosed MDR TB patients (adults and children) with Xpert® MTB/RIF (rifampicin) or Hain MTBDR (Mycobacterium tuberculosis drug resistance), or confirmed with Hain MTBDR plus on positive cultures if initial molecular tests negative or confirmed from MGIT (mycobacteria growth indicator tube) culture/DST if initial molecular tests negative;
• Children (<14 yo) suspected of MDR TB without bacteriological confirmation but documented as a close contact of a confirmed MDR TB patient; AND
• Informed consent to participate in the study signed by the patient or the responsible caretaker for patients <16 years old (as per national legislation).

Only patients with a history of prior treatment with second line anti-TB drugs for less than one month will be eligible for inclusion.

Patients will be included regardless of HIV status.

Exclusion Criteria

• Baseline contraindications to any medications of the study regimen medications, where benefits of the regimen do not outweigh the risks as judged by treating physician;
• Severe renal insufficiency with estimated creatinine clearance of <30 ml/min at baseline (calculated with Cockcroft-Gault formula);
• Patients with extrapulmonary TB only (without involvement of lung parenchyma)
• Patients with documented ofloxacin resistance
• Patients with XDR TB (additional resistance to SLD [second line drug] kanamycin (or capreomycin) AND ofloxacin);
• Patients with resistance to both Km and Cm.
• Critically ill and in the judgement of the treating physician unlikely to survive more than 1 week (these patients may still be commenced on standard MDR TB treatment according to the Karakalpakstan comprehensive TB treatment guidelines)
• Has one or more of the following risk factors for QTc prolongation:
• A confirmed prolongation of QTc interval (Fridericia formula), e.g., repeated demonstration of QTcF (Fridericia correction) interval > 500 ms in the screening ECG (i.e., retesting to reassess eligibility will be allowed once using an unscheduled visit during the screening phase)

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, Republic of Uzbekistan

OTHER_GOV

Sponsor Role: collaborator

Imperial College London

OTHER

Sponsor Role: collaborator

Medecins Sans Frontieres, Netherlands

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philipp du Cros, MBBS

Role: PRINCIPAL_INVESTIGATOR

Medecins sans Frontieres (MSF)

Khamraev A Karimovich, MD

Role: PRINCIPAL_INVESTIGATOR

Ministry of Health, Republic of Uzbekistan

Locations

Outpatient clinics in three districts

Nukus, Karakalpakstan, Uzbekistan

Countries

Uzbekistan

Other Identifiers

MSF MDRTB Uzbek

Identifier Type: -

Identifier Source: org_study_id