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

• ClinicalTrials.gov Identifier: NCT03942354
• Recruitment Status: Unknown
• First Posted: May 8, 2019
• Last Update Posted: May 13, 2021
• Sponsor: Medecins Sans Frontieres, Netherlands
• Collaborators: University of Sussex; London School of Hygiene and Tropical Medicine; THINK TB & HIV Investigative Network; Wits Health Consortium (Pty) Ltd; Ministry of Public Health, Republic of Belarus; Ministry of Health, Republic of Uzbekistan
• Information provided by (Responsible Party): Medecins Sans Frontieres, Netherlands

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Multidrug Resistant Tuberculosis	Drug: Bedaquiline; Drug: Pretomanid; Drug: Moxifloxacin; Drug: Linezolid; Drug: Clofazimine; Drug: Directly observed therapy (DOT)	Phase 2; Phase 3

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Patient-reported Experiences and Quality of Life Outcomes in the TB-PRACTECAL Clinical Trial
• Actual Study Start Date: September 1, 2019
• Estimated Primary Completion Date: September 30, 2022
• Estimated Study Completion Date: October 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention arm; 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; 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.; Other Names: Sirturo; R207910; TMC207; Drug: Pretomanid; 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.; Other Name: PA-824; Drug: Moxifloxacin; Moxifloxacin is an 8-methoxyquinolone class antimicrobial that is a potent inhibitor of DNA gyrase and topoisomerase IV in bacteria; Other Name: Avelox, BAY 12-8039; Drug: Linezolid; 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.; Other Name: Zyvox; Drug: Clofazimine; 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.; Other Name: Lamprene
Active Comparator: Standard therapy; 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); Standard therapy

Outcome Measures

Primary Outcome Measures :

1. Change in St George's respiratory questionnaire SGRQ survey questionnaire from baseline to 12 months [ Time Frame: 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.
2. Changes in Short form 12 survey questionnaire (patient satisfaction and experience) from baseline to 12 months [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Contacts

Contact: Nicola James, MSc; +44 2070674255; nicola.james@london.msf.org

Contact: Charlotte Batts

Locations

Belarus

Republican Scientific and Practical Centre for Pulmonology and Tuberculosis hospital; Recruiting

Minsk, Belarus

Contact: Ernest Nshimiyimana, MD +375336486008 minsk-ct-mtl@oca.msf.org

Principal Investigator: Varvara Solodovnikova, MD

South Africa

Doris Goodwin Hospital; Recruiting

Pietermaritzburg, KwaZulu Natal, South Africa

Contact: Odette van Amsterdam 033 398 0054 O.Amsterdam@thinksa.org.za

Principal Investigator: Ronelle Moodliar, MBBS, MMed

THINK Clinical Trial Unit, Hillcrest; Recruiting

Durban, KwaZulu-Natal, South Africa, 3650

Contact: Seshni Moorgas 0317771009 s.moorgas@think.org.za

Principal Investigator: Ronelle Moodliar, MBBS,MMed

Helen Jospeh Hospital; Recruiting

Johannesburg, South Africa

Contact: Sharon Motlhako +27 11 276 8800 smotlhako@witshealth.co.za

Principal Investigator: Mohammed Rassool, MBChB

Uzbekistan

Republican TB Hospital No. 2; Recruiting

Nukus, Karakalpakstan, Uzbekistan

Contact: Soe Moe, MD +998939200344 NukusCT-med2@oca.msf.org

Principal Investigator: Tigay N Zinaida, MD

Sh Alimov Republican Specialised Scientific-Practical Medical Centre for Phthysiology and Pulmonology Hospital; Recruiting

Tashkent, Uzbekistan

Contact: Pei Sun Aw, MD +998 933881121 tashkent-crc@oca.msf.org

Principal Investigator: Irina Liverko, MD

Sponsors and Collaborators

Medecins Sans Frontieres, Netherlands

University of Sussex

London School of Hygiene and Tropical Medicine

THINK TB & HIV Investigative Network

Wits Health Consortium (Pty) Ltd

Ministry of Public Health, Republic of Belarus

Ministry of Health, Republic of Uzbekistan

Investigators

• Principal Investigator: Beverley Stringer; MSF

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Stringer B, Lowton K, James N, Nyang'wa BT. Capturing patient-reported and quality of life outcomes with use of shorter regimens for drug-resistant tuberculosis: mixed-methods substudy protocol, TB PRACTECAL-PRO. BMJ Open. 2021 Sep 6;11(9):e043954. doi: 10.1136/bmjopen-2020-043954.

• Responsible Party: Medecins Sans Frontieres, Netherlands
• ClinicalTrials.gov Identifier: NCT03942354
• Other Study ID Numbers: PRACTECAL-PRO
• First Posted: May 8, 2019
• Last Update Posted: May 13, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Medecins Sans Frontieres, Netherlands:

Quality of life, drug-resistant tuberculosis

Additional relevant MeSH terms:

Tuberculosis; Tuberculosis, Multidrug-Resistant; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Moxifloxacin; Linezolid; Bedaquiline; Clofazimine; Anti-Bacterial Agents; Anti-Infective Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protein Synthesis Inhibitors; Antitubercular Agents; Anti-Inflammatory Agents; Leprostatic Agents