UMPIRE 2013.

Methods	Randomised, open label, blinded endpoint clinical trial of an FDC-based treatment strategy compared with usual care
Participants	≥18 years old and established CVD or an estimated 5 year CVD risk of 15% or greater in India and 3 European countries (England, Ireland, and the Netherlands)
Interventions	Intervention: one of two versions of the fixed-dose combination ((1) aspirin 75mg, simvastatin40mg, lisinopril 10mg, atenolol 50mgor (2) aspirin75mg, simvastatin 40mg, lisinopril 10mg, hydrochlorothiazide 12.5mg) Control: usual care
Outcomes	Primary: adherence to indicated medications (self-reported current use of antiplatelet, statin, and ≥2 BP-lowering therapies, defined as taking the medication for at least 4 days during the week preceding the visit) at baseline and at the end of the trial and changes in SBP and LDL-C from baseline to the end of the trial Secondary: adherence at 12 months, reasons for stopping cardiovascular medications, quality of life, serious adverse events, and changes in total cholesterol, HDL-C, triglycerides, and creatinine from baseline to 12 months and end of study and cardiovascular events (including coronary heart disease, heart failure leading to death or hospital admission, and cerebrovascular or peripheral arterial disease events)
Notes	Control: inactive/usual care Trial is part of “Single Pill Against Cardiovascular Events (SPACE)” collaboration, which encompasses the “Improving Adherence using Combination Therapy (IMPACT)” and “Kaniyini Guidelines Adherence with the Polypill (Kanyini-GAP)” trials
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation occurred through web-based clinical data management system
Allocation concealment (selection bias)	Low risk	Randomisation occurred through web-based clinical data management system
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants and personnel were unblinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome assessors were blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	At the end of the study, data on self-reported adherence, systolic BP, and LDL-C were available for 1921 (96%), 1849 (92%), and 1807 (90%) randomized participants, respectively
Selective reporting (reporting bias)	Low risk	All primary outcomes reported; quality of life outcomes were not reported in this initial report
Other bias	Unclear risk	Participants randomized to the intervention arm received fixed-dose combination therapy at no cost compared with participants randomized to usual care who were responsible for their drug costs