Multidrug Resistant TuberculosisNCT02496572
Effectiveness of a Simplified Short Regimen for Multidrug Resistant Tuberculosis in Uzbekistan
An observational study of Multidrug Resistant Tuberculosis, run by Medecins Sans Frontieres, Netherlands at 1 site in Uzbekistan.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Multidrug Resistant Tuberculosis
- What is being tested?
- Short course MDR-TB treatment regimen
- How many people
- 110 participants
- Where
- 1 siteUzbekistan
- Study dates
- Sep 2013to Apr 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
Uzbekistan1 site
Outpatient clinics in three districts
Nukus, Karakalpakstan
About this study
Official title: 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.
Read the 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
- Being tested
- Short course MDR-TB treatment regimen
- Keywords
- Tuberculosis, multidrug resistant, Short-course regimen, Medecins sans Frontieres, MSF, Uzbekistan, Ministry of Health
- Medical subject headings
- Tuberculosis, Multidrug-Resistant, Jacobs syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Short course MDR-TB treatment regimenDrug
Also called Bangladesh protocol, Shortened course MDR-TB treatment, 9-month MDR-TB 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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Short course MDR-TB treatment regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of relapse-free success at 12 months follow-up (composite measure of the percentage of patients obtaining cure and treatment completion)
Measured: 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)
Measured: 1 year following completion of a 9-11 month treatment regimen
Rate of adverse events (proportion of patients experiencing at least one adverse event)
Measured: 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)
Measured: 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
Measured: At completion of 9-11 months treatment regimen
Agreement between smear microscopy and culture (expressed as a kappa coefficient)
Measured: 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.
Measured: 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)
Measured: 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 )
Measured: 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)
Measured: 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
Measured: 1 year after completion of 9-11 months treatment regimen
Number of missed days in patients missing >1 day of treatment
Measured: At completion of 9-11 months treatment regimen
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2015 (estimated)
- Study startSep 2013
- Primary completionMar 2016 (estimated)
- Study completionApr 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multidrug Resistant TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medecins Sans Frontieres, Netherlands
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, Republic of Uzbekistan, Imperial College London
- Responsible party
- Sponsor
- Investigators
- Philipp du Cros, MBBS, Principal investigator, Medecins sans Frontieres (MSF)Khamraev A Karimovich, MD, Principal investigator, Ministry of Health, Republic of Uzbekistan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02496572
- Sponsor's protocol ID
- MSF MDRTB Uzbek
- Status last verified
- Jul 2015
- First submitted
- 2 Jul 2014
- Last updated
- 14 Jul 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness of a Simplified Short Regimen for Multidrug Resistant Tuberculosis Treatment in Karakalpakstan, Uzbekistan
- ClinicalTrials.gov ID
- NCT02496572
- Acronym / sponsor ID
- MSF MDRTB Uzbek
- Conditions
- Multidrug Resistant Tuberculosis
- Keywords
- Tuberculosis, multidrug resistant, Short-course regimen, Medecins sans Frontieres, MSF, Uzbekistan, Ministry of Health
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- Medecins Sans Frontieres, NetherlandsUniversity, hospital or other
- Collaborators
- Ministry of Health, Republic of Uzbekistan, Imperial College London
- Study start
- Sep 2013
- Primary completion
- Mar 2016 (estimated)
- Study completion
- Apr 2016 (estimated)
- First posted
- 14 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Short-course MDR-TB regimen patients | – | Drug: Short course MDR-TB treatment regimenShort 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 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (9 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Short course MDR-TB treatment regimenAlso: Bangladesh protocol, Shortened course MDR-TB treatment, 9-month MDR-TB regimenIntensive 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. | Drug | Short-course MDR-TB regimen patients |
Primary outcome
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
11 secondary outcomes
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
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
Rate of treatment interruptions (proportion of patients missing treatment >1 day of complete regimen)
Time frame: 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
Agreement between smear microscopy and culture (expressed as a kappa coefficient)
Time frame: 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
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
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
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
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
Number of missed days in patients missing >1 day of treatment
Time frame: At completion of 9-11 months treatment regimen
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philipp du Cros, MBBS principal investigator
Medecins sans Frontieres (MSF)
Khamraev A Karimovich, MD principal investigator
Ministry of Health, Republic of Uzbekistan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multidrug Resistant Tuberculosis, run by Medecins Sans Frontieres, Netherlands at 1 site in Uzbekistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Uzbekistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2015.