Patient-reported Experiences and Quality of Life Outcomes in the TB-PRACTECAL Clinical Trial

Study Overview
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Brief Summary
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PRACTECAL-PRO is a sub-study of a TB-PRACTECAL clinical trial for multidrug resistant Tuberculosis. It evaluates the effectiveness of TB-PRACTECAL interventions from the patient perspective in terms of their quality of life, shared decision making and satisfaction with services.

Detailed Description
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Tolerability of drugs for TB is a complex and dynamic course for patients with drug resistance and can be affected by many different factors. A deeper understanding of the perspectives and experience of men and women participating in novel TB treatment trials will add to the understanding of the safety and efficacy of treatment. TB-PRACTECAL is a multicentre, open label, phase 2-3 randomised controlled trial evaluating exclusively oral 6 months regimens containing bedaquiline, pretomanid, linezolid +/- moxifloxacin or clofazimine for the treatment of microbiologically confirmed pulmonary M/XDR-TB. It is registered with the ClinicalTrials.gov with identifier number NCT02589782. The trial aims to recruit 630 adults from two sites in Uzbekistan (Nukus and Tashkent) and one site each from Belarus and South Africa. The TB-PRACTECAL trial assumes that even if the investigational arms would have non-inferior efficacy and safety compared to the standard of care outcomes, patients would prefer a shorter, exclusively oral regimen with a lower pill count. This study therefore aims to describe patient experiences (i.e. the quality of the treatment experience as opposed to the quantity of treatment or the amount of time spent on it). The PRACTECAL-PRO sub-study aims to answer the question: What are the perceptions, expectations and experiences of novel TB treatment for adult patients participating in a six-month regimen clinical trial in Uzbekistan, South Africa and Belarus? The objectives for the analysis are: To compare baseline scores between trial patients (all interventional arm patients plus standard of care patients) with healthy controls. To assess changes in scores over time in patients on the intervention arms and patients on the standard of care arm. To assess the utility of the SF 12 and SGRQ in a TB clinical trial.

Official Title
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Patient-reported Experiences and Quality of Life Outcomes in the TB-PRACTECAL Clinical Trial

Conditions
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Multidrug Resistant Tuberculosis

Intervention / Treatment
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* Drug: Bedaquiline
* Drug: Pretomanid
* Drug: Moxifloxacin
* Drug: Linezolid
* Drug: Clofazimine
* Drug: Directly observed therapy (DOT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients recruited into the TB-PRACTECAL trial in the approved sites OR Local healthy-controls of a similar profile in terms of age and gender aged ≥18 years AND Literate in the study questionnaire languages Able to sign the sub-study informed consent form after agreeing to the additional interviews and completion of questionnaires. Exclusion Criteria: TB patients excluded from TB-PRACTECAL clinical trial Healthy volenteers with co-morbidities Healthy volenteers found to have TB

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention arm<br>A total of 72 intervention arm trial patients (from TB-PRACTECAL trial) are anticipated across all three sites: South Africa, Belarus, and Karakalpakstan. | Drug: Bedaquiline<br>* Bedaquiline is a diarylquinoline class antimicrobial which blocks the proton pump for ATP synthase of mycobacteria. This in turn blocks the ATP production required for cellular energy production and leading to cell death.<br>* Other names: TMC207;Drug: Pretomanid<br>* Pretomanid is a nitroimidazole class antimicrobial which interferes with cell wall biosynthesis in mycobacteria. It may have other mechanisms of action as well in non-replicating mycobacteria.<br>* Other names: PA-824;Drug: Moxifloxacin<br>* Moxifloxacin is an 8-methoxyquinolone class antimicrobial that is a potent inhibitor of DNA gyrase and topoisomerase IV in bacteria<br>* Other names: Avelox, BAY 12-8039;Drug: Linezolid<br>* Linezolid, an oxazolidinone class antimicrobial which works by inhibiting ribosomal protein synthesis. It is approved for Gram-positive bacterial infections, and is increasingly being used for drug resistant TB disease.<br>* Other names: Zyvox;Drug: Clofazimine<br>* Clofazimine is a lipophilic riminophenazine licensed for treatment of leprosy. Its mechanism(s) of action remains unclear, but existing evidence suggests production of reactive oxygen species within Mycobacterium tuberculosis is one mechanism.<br>* Other names: Lamprene;|
| Active Comparator: Standard therapy<br>72 standard therapy trial patients (from TB-PRACTECAL trial) will be recruited across all three sites. Patients will complete measures at baseline, 3 months, 6 months and 12 months. | Drug: Directly observed therapy (DOT)<br>* Standard therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in St George's respiratory questionnaire SGRQ survey questionnaire from baseline to 12 months | To assess the quality of life (QoL) of trial patients from baseline to 12 months: both those treated in the investigational arms and the standard of care arm. For the SGRQ, a change of 4 points is suggested to indicate a clinically significant change, although the questionnaire was developed with patients who had COPD rather than TB. In the sub-study with a relatively small sample we cannot be confident about whether a change of 4 points represents a similarly significant change, but we will be mindful to assess this possibility. Ultimate aim is to determine whether disease-specific patient quality of life scores improve in investigational arm patients from baseline to successful completion of treatment. | 12 months | 
| Changes in Short form 12 survey questionnaire (patient satisfaction and experience) from baseline to 12 months | Two summary scores are reported from the SF-12 - a mental component score (MCS-12) and a physical component score (PCS-12). The scores may be reported as Z-scores (difference compared to the population average, measured in standard deviations). Ultimate aim is to determine whether disease-specific patient satisfaction scores improve in investigational arm patients from baseline to successful completion of treatment. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Quality of life, drug-resistant tuberculosis