Adjunctive Acetylsalicylic Acid and Ibuprofen for Tuberculosis

Prior treatment

• Has a comorbid condition where treatment with aspirin, ibuprofen or other NSAID is indicated (e.g. cardiovascular disease, rheumatic fever, chronic pain, etc.)
• 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.
• 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
• 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.

Other illness

• 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.
• History or clinical record of sensitivity, asthma or allergy that could be attributed to NSAIDs
• 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.
• 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.

Lab values

• 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

Other

• 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.
• Weight < 45kg at baseline.
• 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).

• 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.