Phase 2b Randomized Double-blind, Placebo-controlled Trial to Estimate the Potential Efficacy and Safety of Two Repurposed Drugs, Acetylsalicylic Acid and Ibuprofen, for Use as Adjunct Therapy Added to, and Compared With, the Standard WHO-recommended TB Regimen (SMA-TB)
Overview
- Phase
- Phase 2
- Intervention
- SoC TB
- Conditions
- Tuberculosis, Pulmonary
- Sponsor
- Fundació Institut Germans Trias i Pujol
- Enrollment
- 354
- Locations
- 3
- Primary Endpoint
- Hazard ratio for time to stable culture conversion (SCC)
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Adults, 18- 60 years of age
- •Written informed consent in a language they understand. This includes informed consent to be in the trial and informed consent to collect specimens.
- •Laboratory confirmed pulmonary TB (with or without extrapulmonary involvement) defined as a hard copy of a sputum laboratory result that reports M. tuberculosis (Mtb) detection by a WHO-recommended assay -both rapid molecular assays or mycobacterial culture with subsequent speciation are acceptable as inclusion criteria.
- •Women of childbearing potential (including females \<2 years post-menopausal) must have a negative pregnancy test at enrolment.
- •Participants must be willing to have an HIV test done unless there is compelling evidence that the patient is HIV-infected at the time of randomization.
Exclusion Criteria
- •Has a comorbid condition where treatment with aspirin, ibuprofen or other NSAID is indicated (e.g. cardiovascular disease, rheumatic fever, chronic pain, etc.)
- •People institutionalized (incarceration in jail or prison, or due to chronic mental illness). If incarcerated during the study, participants may be terminated, those incarcerated in the first 8 weeks of follow up will be late exclusions and replaced\*. Patients either who are planned to be hospitalized or currently hospitalized whilst treated for MDR TB in a TB hospital or ward may be enrolled.
- •Receipt of multi-drug TB treatment (including rifamycin plus isoniazid preventive treatment regimens) for ≥3 days in the 6 months prior to randomization. Participants who have received ≥3 days of TB preventive treatment in the month prior to TB treatment initiation will also be excluded.
- •Currently Pregnancy/breastfeeding. Women who conceive and are found to be pregnant in the first 4 weeks of the trial will be terminated from the trial and excluded from the analysis.
- •Any of the following laboratory parameters taken prior to randomization:
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 x upper limit of normal (ULN);
- •Total bilirubin \> 2 x ULN;
- •Neutrophil count ≤ 700 neutrophils /mm3;
- •Platelet count \< 50,000 cells / mm3
- •Haemoglobin concentration less than 8 g/dL
Arms & Interventions
SoC TB + IBU group
Standard of Care (SoC) TB treatment + ibuprofen 400mg twice daily during first 4 weeks of TB treatment followed by ibuprofen 400mg once daily for an additional 4 weeks
Intervention: SoC TB
SoC TB + IBU group
Standard of Care (SoC) TB treatment + ibuprofen 400mg twice daily during first 4 weeks of TB treatment followed by ibuprofen 400mg once daily for an additional 4 weeks
Intervention: IBU group
Control group
Standard of Care (SoC) TB treatment + placebo twice daily during first 4 weeks of TB treatment followed by placebo once daily for an additional 4 weeks.
Intervention: Control group
Control group
Standard of Care (SoC) TB treatment + placebo twice daily during first 4 weeks of TB treatment followed by placebo once daily for an additional 4 weeks.
Intervention: SoC TB
SoC TB + ASA group
Standard of Care (SoC) TB treatment + acetylsalicylic acid 300mg twice daily during first 4 weeks of TB treatment followed by aspirin 300mg once daily for an additional 4 weeks.
Intervention: ASA group
SoC TB + ASA group
Standard of Care (SoC) TB treatment + acetylsalicylic acid 300mg twice daily during first 4 weeks of TB treatment followed by aspirin 300mg once daily for an additional 4 weeks.
Intervention: SoC TB
Outcomes
Primary Outcomes
Hazard ratio for time to stable culture conversion (SCC)
Time Frame: 24 weeks of TB treatment
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 to ≥ 67% sustained reduction in the TB score
Time Frame: Week 8 of follow-up
Time to ≥ 67% sustained reduction in the TB score over the course of TB treatment
Secondary Outcomes
- 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.(At baseline, week 8 and week 24)
- Changes in the BCN-SA Radiological Score Value.(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.(At week 8, week 24 and for MDR TB patients at the end of treatment)
- Hazard ratio for stable culture conversion (SCC) at week 8 and week 16 after treatment start.(At week 8 and week 16)
- Proportion of patients with improvement or resolution of clinical signs and symptoms at end of treatment (TB score).(At week 24)