The purpose of this study is to assess the efficacy and safety of 2 repurposed drugs (acetylsalicylic acid and ibuprofen), for use as adjunct therapy added to, and compared with, the standard of care (SoC) WHO-recommended TB regimen in drug-sensitive (DS) and multi-drug resistant (MDR) TB patients.
If eligible and informed consent obtained, patients will be randomized 1:1:1 into one of the following 3 arms, to receive: 1. Standard of Care (SoC) TB treatment + placebo twice daily during the first 4 weeks of TB treatment followed by placebo once daily for an additional 4 weeks. (control group). 2. SoC TB treatment + acetylsalicylic acid 300mg twice daily during the first 4 weeks of TB treatment followed by acetylsalicylic acid 300mg once daily for an additional 4 weeks. 3. SoC TB treatment + ibuprofen 400mg twice daily during the first 4 weeks of TB treatment followed by ibuprofen 400mg once daily for an additional 4 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
426
placebo 2 months treatment: 2 tablets during 4 weeks + 1 tablet during 4 weeks
Acetylsalicylic acid 2 months treatment: 2 tablets during 4 weeks (600 mg daily) + 1 tablet during 4 weeks (300 mg daily)
Ibuprofen 2 months treatment: 2 tablets during 4 weeks (800 mg daily) + 1 tablet during 4 weeks (400 mg daily)
National Center for Tuberculosis and Lung Diseases
Tbilisi, Georgia
Perinatal HIV Unit (PHRU)- Chris Hani Baragwanath Hospital
Soweto, Johannesburg, South Africa
PHRU- Matlosana, Tshepong Hospital MDR Unit
Klerksdorp, Matlosana, South Africa
Time to ≥ 67% Sustained Reduction in the TB Score
Time taken to reach 67% sustained reduction in the TB score over the course of TB treatment. Minimum value of the score = 0; Maximum value = 13). Higher scores mean a better or worse outcome. Difference between each intervention arm and control group were analysed. The TB Score has been described to be useful to monitor good response to TB treatment, regardless of HIV status.
Time frame: 24 weeks of TB treatment
Time to Stable Culture Conversion (SCC)
Time to SCC is defined as the time until at least 2 consecutive negative cultures for M. tuberculosis at least 4 weeks apart during the first 24 weeks of TB treatment.
Time frame: 24 weeks of TB treatment
Time to a Stable Culture Conversion (SCC) at Week 8 and Week 16 After Treatment Initiation
Time to SCC is defined as the time until at least 2 consecutive negative cultures for M. tuberculosis at least 4 weeks apart. For this secondary outcome, differences between groups were analyzed at week 8 and week 16
Time frame: Week 8 and Week 16
Improvement or Resolution of Clinical Signs and Symptoms
Signs and symptoms were assessed using the TB Score (TBS), which ranges from 0 to 13, with higher scores indicating more severe disease. The outcome was defined as the proportion of participants achieving a ≥50% reduction from baseline in TBS at Week 8 and a ≥75% reduction from baseline in TBS at Week 24. Comparisons were performed between each intervention arm and the control group. TBS has been described as a useful tool for monitoring clinical response to tuberculosis treatment.
Time frame: Baseline, week 8 and week 24
Improvement of Lung Function
Improvement of lung function in the 1-second forced expiratory volume (FEV1)
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Standard of Care Tuberculosis treatment
Time frame: Baseline, week 8 and week 24
Reduction of the Activity Component of the RTBES
Changes in chest X-ray (CXR) findings were assessed using the Activity component of the RUTI TB Evolution Score (RTBES). The baseline CXR served as the reference for comparison with subsequent CXRs obtained during tuberculosis treatment. The Activity component ranges from 0 to 38, with higher scores indicating more severe radiographic involvement. The outcome was defined as the proportion of participants achieving a ≥50% reduction from baseline in the Activity component at Week 8 and a ≥75% reduction from baseline at Week 24. Comparisons were performed between each intervention arm and the control group.
Time frame: Baseline, week 8 and week 24
Improvement of Health-related Quality of Life
Number of patients showing improvement in health-related quality of life at weeks 8 and 24 compared to baseline, as measured by the Saint Georges Respiratory Questionnaire (SGRQ). The SGRQ score ranges from 0 (best) to 100 (worst), with scores up to 7 considered to be within the healthy range. Improvement in this study being defined as achieving a score within the healthy range.
Time frame: Baseline, week 8 and week 24