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

NCT02496572 | Unknown DMC

• 1 other identifier: MSF MDRTB Uzbek
• Study Type: observational
• Target: 110
• Locations: 1 country
• Sites: 1

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.

Conditions

Multidrug Resistant Tuberculosis

Keywords

Tuberculosis, multidrug resistant; Short-course regimen; Medecins sans Frontieres, MSF; Uzbekistan, Ministry of Health

Outcome Measures

Primary Outcomes (1)

• Rate of relapse-free success at 12 months follow-up (composite measure of the percentage of patients obtaining cure and treatment completion)

  End of treatment to 1 year following completion of a 9-11 month treatment regimen

Secondary Outcomes (11)

• Predictive value of 1st and 2nd line drug resistance at baseline on treatment outcomes (proportion classified as sensitive amongst ethambutol, pyrazinamide, capreomycin and kanamycin)

  1 year following completion of a 9-11 month treatment regimen

• Rate of adverse events (proportion of patients experiencing at least one adverse event)

  1 year following completion of a 9-11 month treatment regimen

• Rate of treatment interruptions (proportion of patients missing treatment >1 day of complete regimen)

  At completion of 9-11 months treatment regimen

• Rate of unfavorable outcomes whilst on treatment (composite of patients with default, death, failure) during study period

  At completion of 9-11 months treatment regimen

• Agreement between smear microscopy and culture (expressed as a kappa coefficient)

  At completion of 9-11 months treatment regimen

Study Arms (1)

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

Drug: Short course MDR-TB treatment regimen

Interventions

Short course MDR-TB treatment regimen 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.

Also known as: Bangladesh protocol, Shortened course MDR-TB treatment, 9-month MDR-TB regimen

Short-course MDR-TB regimen patients

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients will be referred from the facilities described below in three districts in Karakalpakstan, Uzbekistan 1. Kegeily Rayon: Kegeily rayon is a large rayon (district) with a population of 83,000. The rayon has 2 Polyclinics (outpatient clinics for TB care) and 21 SVPs (general practice surgeries with staff trained in TB care). 2. Shumanay Rayon. A small rayon close to Khodjeily rayon with a population of 52,000. There is 1 Polyclinic and 9 SVPs in the rayon 3. Nukus City Nukus city is the largest district in Karakalpakstan with a population of 268 000. There are 9 polyclinics.

You may qualify if:

• 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).
• Patients will be included regardless of HIV status.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Medecins Sans Frontieres, Netherlands: lead
• Ministry of Health, Republic of Uzbekistan: collaborator
• Imperial College London: collaborator

Study Sites (1)

Outpatient clinics in three districts

Nukus, Karakalpakstan, Uzbekistan

Location

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant; Jacobs syndrome

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Philipp du Cros, MBBS

  Medecins sans Frontieres (MSF)

  PRINCIPAL INVESTIGATOR

• Khamraev A Karimovich, MD

  Ministry of Health, Republic of Uzbekistan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2014
• First Posted: July 14, 2015
• Study Start: September 1, 2013
• Primary Completion: March 1, 2016
• Study Completion: April 1, 2016
• Last Updated: July 14, 2015

Record last verified: 2015-07

Locations

UZ (1)