- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02496572
Effectiveness of a Simplified Short Regimen for Multidrug Resistant Tuberculosis in Uzbekistan
Effectiveness of a Simplified Short Regimen for Multidrug Resistant Tuberculosis Treatment in Karakalpakstan, Uzbekistan
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Locations
-
-
Karakalpakstan
-
Nukus, Karakalpakstan, Uzbekistan
- Outpatient clinics in three districts
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Patients will be referred from the facilities described below in three districts in Karakalpakstan, Uzbekistan
- 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).
- 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
- Nukus City Nukus city is the largest district in Karakalpakstan with a population of 268 000. There are 9 polyclinics.
Description
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)
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
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 |
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Rate of relapse-free success at 12 months follow-up (composite measure of the percentage of patients obtaining cure and treatment completion)
Time Frame: End of treatment to 1 year following completion of a 9-11 month treatment regimen
|
End of treatment to 1 year following completion of a 9-11 month treatment regimen
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Predictive value of 1st and 2nd line drug resistance at baseline on treatment outcomes (proportion classified as sensitive amongst ethambutol, pyrazinamide, capreomycin and kanamycin)
Time Frame: 1 year following completion of a 9-11 month treatment regimen
|
1 year following completion of a 9-11 month treatment regimen
|
Rate of adverse events (proportion of patients experiencing at least one adverse event)
Time Frame: 1 year following completion of a 9-11 month treatment regimen
|
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)
Time Frame: At completion of 9-11 months treatment 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
Time Frame: At completion of 9-11 months treatment regimen
|
At completion of 9-11 months treatment regimen
|
Agreement between smear microscopy and culture (expressed as a kappa coefficient)
Time Frame: At completion of 9-11 months treatment regimen
|
At completion of 9-11 months treatment regimen
|
Proportion of patients with amplification in drug resistance (defined as a patient previously testing sensitive to a drug who subsequently tests resistant) on follow-up drug susceptibility testing compared with baseline.
Time Frame: 1 year after completion of 9-11 months treatment regimen
|
1 year after completion of 9-11 months treatment regimen
|
Rate of treatment modifications (composite measure of proportion of patients requiring cessation or replacement of a drug due to adverse events not described in the protocol)
Time Frame: At completion of 9-11 months treatment regimen
|
At completion of 9-11 months treatment regimen
|
Rate of successful outcomes at end of treatment (composite of patients with treatment outcomes cured and completed )
Time Frame: At completion of 9-11 months treatment regimen
|
At completion of 9-11 months treatment regimen
|
Rate of adverse events by organ group (categorised as cardiac, respiratory, gastrointestinal, auditory, systemic, dermatological, opthalmologic, neurological, other)
Time Frame: 1 year after completion of 9-11 months treatment regimen
|
1 year after completion of 9-11 months treatment regimen
|
Severity of adverse events (proportion of adverse events classified as mild, moderate, severe and potentially life-threatening) as per DAID criteria
Time Frame: 1 year after completion of 9-11 months treatment regimen
|
1 year after completion of 9-11 months treatment regimen
|
Number of missed days in patients missing >1 day of treatment
Time Frame: At completion of 9-11 months treatment regimen
|
At completion of 9-11 months treatment regimen
|
Collaborators and Investigators
Investigators
- Principal Investigator: Philipp du Cros, MBBS, Medecins sans Frontieres (MSF)
- Principal Investigator: Khamraev A Karimovich, MD, Ministry of Health, Republic of Uzbekistan
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- MSF MDRTB Uzbek
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Multidrug Resistant Tuberculosis
-
Otsuka Pharmaceutical Development & Commercialization...CompletedMultidrug-resistant TuberculosisSouth Africa, Estonia, Philippines, Peru, Lithuania, Latvia, Moldova, Republic of
-
Janssen Research & Development, LLCRecruitingMultidrug-Resistant TuberculosisMozambique, Philippines, Russian Federation, South Africa, Uganda, Ukraine
-
University of Cape TownBaylor Research InstituteCompletedMultidrug-resistant TuberculosisSouth Africa
-
University of Cape TownUniversity of Stellenbosch; University of Cape Town Lung Institute; University... and other collaboratorsCompletedTuberculosis | Multidrug Resistant Tuberculosis | Extensively-drug Resistant TuberculosisSouth Africa
-
University Medical Center GroningenCompletedMultidrug-resistant Tuberculosis | Extensively Drug-resistant TuberculosisNetherlands
-
Foundation for Innovative New Diagnostics, SwitzerlandInstitute of Tropical Medicine, Belgium; Research Center Borstel; National Institute...CompletedMultidrug-Resistant Tuberculosis | Isoniazid Resistant Pulmonary Tuberculosis | Rifampicin Resistant Tuberculosis | Pulmonary Tuberculoses
-
National Institute of Allergy and Infectious Diseases...Eunice Kennedy Shriver National Institute of Child Health and Human Development... and other collaboratorsRecruitingTuberculosis, MDRHaiti, Tanzania, Thailand, Botswana, Brazil, India, Kenya, Peru, Philippines, South Africa, Uganda, Zimbabwe, Vietnam
-
Otsuka Pharmaceutical Development & Commercialization...TerminatedTuberculosisLatvia, Lithuania
-
Otsuka Pharmaceutical Development & Commercialization...CompletedMultidrug Resistant TuberculosisPhilippines, South Africa
-
Huashan HospitalUnknownMultidrug Resistant TuberculosisChina
Clinical Trials on Short course MDR-TB treatment regimen
-
Shanghai Pulmonary Hospital, Shanghai, ChinaHuashan Hospital; Shanghai Public Health Clinical Center; Anhui Chest Hospital; No.85 Hospital, Changning, Shanghai, China and other collaboratorsRecruiting
-
National Institute of Allergy and Infectious Diseases...Otsuka Pharmaceutical Development & Commercialization, Inc.RecruitingHIV Infections | TuberculosisTanzania, India, South Africa, Botswana
-
National Institute of Allergy and Infectious Diseases...Eunice Kennedy Shriver National Institute of Child Health and Human Development... and other collaboratorsRecruitingTuberculosis | Rifampicin Resistant TuberculosisBrazil, India, South Africa, Tanzania, Thailand
-
IRCCS Azienda Ospedaliero-Universitaria di BolognaRecruitingEsophageal Cancer | Palliative Care | RadiotherapyItaly
-
IRCCS Azienda Ospedaliero-Universitaria di BolognaRecruitingThoracic Cancer | Palliative Care | RadiotherapyItaly
-
IRCCS Azienda Ospedaliero-Universitaria di BolognaRecruitingPelvic Cancer | Palliative Care | RadiotherapyItaly
-
IRCCS Azienda Ospedaliero-Universitaria di BolognaRecruitingPalliative Care | Brain Metastases | RadiotherapyItaly
-
IRCCS Azienda Ospedaliero-Universitaria di BolognaRecruitingHead and Neck Cancer | Palliative Care | RadiotherapyItaly
-
IRCCS Azienda Ospedaliero-Universitaria di BolognaRecruitingPalliative Care | Radiotherapy | Abdomen TumorsItaly
-
IRCCS Azienda Ospedaliero-Universitaria di BolognaRecruitingBone Metastases | Palliative Care | RadiotherapyItaly