Using acetylsalicylic acid and ibuprofen to treat tuberculosis
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)
This study is testing if adding acetylsalicylic acid or ibuprofen to the usual treatment for tuberculosis can help people get better faster.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 354 (estimated) |
| Ages | 18 Years to 60 Years |
| Sex | All |
| Sponsor | Fundació Institut Germans Trias i Pujol Academic / other |
| Locations | 3 sites (Tbilisi and 2 other locations) |
| Trial ID | NCT04575519 on ClinicalTrials.gov |
What this trial studies
This study evaluates the efficacy and safety of two repurposed medications, acetylsalicylic acid and ibuprofen, as adjunct therapies to the standard treatment for drug-sensitive and multi-drug resistant tuberculosis. Eligible participants will be randomized into three groups: one receiving standard care with a placebo, another receiving standard care with acetylsalicylic acid, and the third receiving standard care with ibuprofen. The treatment duration is eight weeks, with specific dosing schedules for each group. The aim is to determine if these medications can enhance the effectiveness of the current tuberculosis treatment regimen.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18-60 with laboratory-confirmed pulmonary tuberculosis.
Not a fit: Patients with comorbid conditions requiring NSAID treatment or those with contraindications to aspirin or ibuprofen may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could improve treatment outcomes for patients with tuberculosis, particularly those with drug-resistant forms of the disease.
How similar studies have performed: While the use of adjunctive therapies in tuberculosis treatment is being explored, the specific combination of acetylsalicylic acid and ibuprofen in this context is novel and has not been extensively tested.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. Adults, 18- 60 years of age
2. Written informed consent in a language they understand. This includes informed consent to be in the trial and informed consent to collect specimens.
3. 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.
4. Women of childbearing potential (including females \<2 years post-menopausal) must have a negative pregnancy test at enrolment.
5. 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:
1. Has a comorbid condition where treatment with aspirin, ibuprofen or other NSAID is indicated (e.g. cardiovascular disease, rheumatic fever, chronic pain, etc.)
2. 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.
3. 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.
4. 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.
5. 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
* Serum creatinine concentration more than twice the upper limit of normal
6. Co-treatment in the three months prior to randomization, or planned treatment over the course of the trial follow up with any one of the following agents:
* anticoagulant therapy
* immune modulating therapy (cancer treatments, any oral or daily use of inhaled steroids;
* Antacids or proton pump inhibitors - including self-treatment and prescription
7. History or clinical record of sensitivity, asthma or allergy that could be attributed to NSAIDs
8. Weight \< 45kg at baseline.
9. History or clinical record suggestive of any of the following in the past two years:
* peptic ulcer disease or gastro-intestinal bleeding,
* coagulopathy or other bleeding disorder,
* renal disease requiring hospitalization - in addition, any prior record at any time of acute kidney injury will be an exclusion criterion.
* liver disease requiring further investigation or hospitalization,
* underlying cardiovascular disease or risk factors for cardiovascular disease.
10. Patients with HIV infection (irrespective of ART status) if:
* CD4 \<350 cells/mm3
* if on ART, unsuppressed (\>200 copies/ml) viral load
* if not on ART, either in the opinion of the attending doctor or according to local ART guidelines, the patient should initiate ART during the 8-week initial placebo or NSAID treatment phase.
11. Alcohol use: potential participant either self-reports or in the investigator's opinion that the patient drinks more than an average of four units/day over a usual week or is a binge drinker (men: 5 or more drinks; women: consume 4 or more drinks, in about 2 hours).
12. Major co-morbid conditions or any other finding which in the opinion of the investigator would compromise the protocol compliance or significantly influence the interpretation of results.
Where this trial is running
Tbilisi and 2 other locations
- National Center for Tuberculosis and Lung Diseases — Tbilisi, Georgia (Recruiting)
- Perinatal HIV Unit (PHRU)- Chris Hani Baragwanath Hospital — Soweto, Johannesburg, South Africa (Recruiting)
- PHRU- Matlosana, Tshepong Hospital MDR Unit — Klerksdorp, Matlosana, South Africa (Recruiting)
Study contacts
- Study coordinator: Cristina Vilaplana, MD, PhD
- Email: cvilaplana@igtp.cat
- Phone: +34930330527
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.