Table 1.

Inclusion and exclusion criteria

Inclusion criteria	Exclusion criteria
1. Adults, 18–60 years of age	1. Has a comorbid condition where treatment with ASA, Ibu, or other NSAID is indicated (e.g. cardiovascular disease, rheumatic fever, chronic pain)
2. Written informed consent in a language they understand. This includes informed consent to be in the trial and informed consent to collect specimens	2. People institutionalized (incarceration in jail or prison or due to chronic mental illness). If incarcerated during the study, participants may be terminated, and those incarcerated in the first 8 weeks of follow-up will be late exclusions and replaceda. Patients either who are planned to be hospitalized or are currently hospitalized while treated for MDR-TB in a TB hospital or ward may be enrolled
3. Laboratory-confirmed pulmonary TB (with or without extrapulmonary involvement) defined as a hard copy of a sputum laboratory result that reports Mtb detection by a WHO-recommended assay—both rapid molecular assays (MTB/RIF or MTB/RIF ULTRA GeneXpertwith semiquantitative result of ‘medium’ or ‘high’) or mycobacterial culture with subsequent speciation are acceptable as inclusion criteria Patients who are subsequently found to be culture negative for Mtb at baseline will be late exclusions and not included in the analysisa	3. Receipt of multi-drug TB treatment (including rifamycin plus isoniazid preventive treatment regimens) for > 4 days in the 6 months prior to randomization. Participants who have received > 4 days of TB preventive treatment in the month prior to TB treatment initiation will also be excluded
4. Women of childbearing potential (including females < 2 years post-menopausal) must have a negative pregnancy test at enrolment Women who become pregnant during the first 8 weeks of the study will have the study drug stopped immediately. If pregnancy occurs during the first 4 weeks, the participant will be excluded from the analysisc	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 analysisa
5. Participant 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. Compelling evidence of HIV infection are as follows: • Hard copy of an unsuppressed viral load • Hard copy of a prescription for antiretroviral therapy • Documentation in the clinical record of two rapid tests positive for HIV infection • Hard copy of a laboratory ELISA or Western blot test positive for HIV	5. Any of the following laboratory parameters taken prior to randomization: • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 × upper limit of normal (ULN) • Total bilirubin > 2 × 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 3 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 < 45 kg at baseline
	9. A history or clinical record suggestive of any of the following in the past 2 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 if: • CD4 < 100 cells/mm3 (taken within 3 months prior to consent) • If on ART, viral load > 400 copies/ml) (taken within 3 months prior to consent) • 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 abuse: 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 h)b
	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

^aLate exclusion criteria: These are criteria which become apparent after randomization (and after likely receipt of the study drug). Where possible, participants who are late exclusions during the initial 8 weeks placebo or NSAID treatment phase will be replaced by another eligible participant

^b1 unit of alcohol is equivalent to 8 g of ethanol, the amount that can be processed by the average adult in an hour (UK specifications). One tot (25 ml) of alcoholic spirits, half a glass of wine, and 284 ml of beer are roughly equivalent to one unit of alcohol

^cIn South Africa, pregnancy tests will be done at every visit for the first 8 weeks due to high rates of pregnancy