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
354
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
RECRUITINGPerinatal HIV Unit (PHRU)- Chris Hani Baragwanath Hospital
Soweto, Johannesburg, South Africa
RECRUITINGPHRU- Matlosana, Tshepong Hospital MDR Unit
Klerksdorp, Matlosana, South Africa
RECRUITINGTime to ≥ 67% sustained reduction in the TB score
Time to ≥ 67% sustained reduction in the TB score over the course of TB treatment
Time frame: Week 8 of follow-up
Hazard ratio for time to stable culture conversion (SCC)
Hazard ratio for time to stable culture conversion (SCC), 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
Hazard ratio for stable culture conversion (SCC) at week 8 and week 16 after treatment start.
Difference between each intervention arm and control group
Time frame: At week 8 and week 16
Proportion of patients with improvement or resolution of clinical signs and symptoms at end of treatment (TB score).
Difference between each intervention arm and control group
Time frame: At week 24
Proportion of patients with improvement of lung function impairment as change from baseline at week 8, 24 and end of treatment in the 1-second forced expiratory volume (FEV1) expressed as FEV1.
Difference between each intervention arm and control group
Time frame: At baseline, week 8 and week 24
Changes in the BCN-SA Radiological Score Value.
Change in chest-X ray (measured with the BCN-SA score) using the x-ray taken at baseline as the comparator compared with subsequent x-rays over the course of TB therapy. Difference between each intervention arm and control group. The BCN-SA Radiological Score Value assesses the sum of acute and chronic findings in the chest X-ray. Per each finding, a minimum score of 0 and a maximum score of 8 is recorded. The total score value is calculated by adding all the individual findings score values. Higher values of total score represent a worse outcome.
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Standard of Care Tuberculosis treatment
Time frame: At baseline, week 8, week 24 (and month 12 if MDR)
Number of patients with improvement of Health-related Quality of Life comparing baseline measure with that over the course of therapy.
Difference between each intervention arm and control group
Time frame: At week 8, week 24 and for MDR TB patients at the end of treatment