Flack 2003.

Methods	Study design: randomized controlled trial Study grouping: parallel group
Participants	Baseline characteristics Eplerenone 50 mg daily Female (%): 64.3 (117/182) Age (years, mean ±SD): 50.9 ± 11.2 Black (%): 63.2 (115/182) Weight female (kg, mean ±SD): 86.5 ± 18.5 Weight male (kg, mean ±SD): 92.7 ± 17.4 Seated SBP (mmHg, mean ±SD): 149.3 ± 11.3 Seated DBP (mmHg, mean ±SD): 98.9 ± 3.5 HR (beats/min, mean ±SD): 73.6 ± 8.3 UA/CR (ug/mmol): 941 Active renin (mU/L): 11.3 Serum aldosterone (ng/dL): 7.0 Placebo Female (%): 53.6 (97/181) Age (years, mean ±SD): 52.1 ± 11.1 Black (%): 62.4 (113/181) Weight female (kg, mean ±SD): 83.9 ± 18.9 Weight male (kg, mean ±SD): 93.2 ± 16.9 Seated SBP (mmHg, mean ±SD): 148.9 ± 11.6 Seated DBP (mmHg, mean ±SD): 99.1 ± 3.6 HR (beats/min, mean ±SD): 73.1 ± 8.9 UA/CR (ug/mmol): 991 Active renin (mU/L): 12.0 Serum aldosterone (ng/dL): 7.5 Inclusion criteria: Men and women ≥ 18 years old Mild‐to‐moderate hypertension (SBP < 180 mmHg and DBP 95‐109 mmHg without medication) Self‐identified as black or white Patients on 1 or 2 antihypertensives and BP < 140/90 Exclusion criteria: Patients with known secondary hypertension, insulin‐dependent diabetes, hepatic disease, elevated serum creatinine levels, evidence of alcohol/drug abuse, unable to be withdrawn from antihypertensives, regularly used corticosteroids, class II to IV heart failure, myocardial infarction, coronary revascularization, stroke or transient ischemic attack within past 6 months, current unstable angina, or any serious medical condition (not described) History of NYHA II‐IV congestive heart failure Myocardial infarction, coronary revascularization, stroke, or TIA within the past 6 months Current unstable angina Any serious medical condition Pretreatment: missing baseline data for serum aldosterone in N = 61 (placebo); missing baseline UA/CR for N = 63 (placebo) and N = 50 (eplerenone); missing baseline RAAS profile in N = 60 (placebo) and N = 45 (eplerenone). They report no significant differences between the three groups, but higher % female in eplerenone group (64.3% vs 53.6%)
Interventions	Intervention characteristics Eplerenone 50 mg daily Placebo
Outcomes	Mean change in SBP Outcome type: continuous outcome Reporting: fully reported Unit of measure: mmHg Direction: lower is better Data value: change from baseline Mean change in DBP Outcome type: continuous outcome Reporting: fully reported Unit of measure: mmHg Direction: lower is better Data value: change from baseline Any adverse event Outcome type: adverse event Reporting: fully reported Direction: lower is better Data value: endpoint Adverse event leading to discontinuation Outcome type: adverse event Direction: lower is better Data value: endpoint
Identification	Sponsorship source: Pharmacia Corporation, Skokie Illinois Country: South Africa and USA Setting: 8 centers in South Africa, 41 centers in USA Comments: 4 January 2000 to 19 January 2001 Author's name: John M Flack Institution: Department of Internal Medicine, Wayne State University, Detroit, Michigan Email: JFlack@intmed.wayne.edu Address: 4201 St. Antoine, Suite 2EDetroit, Michigan 48201
Notes	—
Risk of bias
Bias	Authors' judgement	Support for judgement
Sequence Generation	Unclear risk	Judgement comment: method of sequence generation not described
Allocation concealment	Unclear risk	Judgement comment: method of allocation concealment not described
Blinding of participants and personnel All outcomes	Unclear risk	Quote: "double‐blind" Judgement comment: not described how blinding was achieved or which participants were blinded
Blinding of outcome assessors All outcomes	Unclear risk	Judgement comment: blinding of outcome assessors not described
Incomplete outcome data All outcomes	High risk	Quote: "A total of 551 patients were randomized to study treatment, and 352 completed 16 weeks of treatment. Of these, 16 patients (4 placebo, 8 eplerenone, and 4 losartan) had no post‐baseline assessment; therefore, 535 patients were included in the cohort for efficacy analysis (Table 1)." Judgement comment: 16 patients had no post baseline assessment and were not included in the efficacy analysis. Blood pressure data from these 16 patients was not known.
Selective outcome reporting	Unclear risk	Quote: "The primary study end point was the mean change in DBP from baseline to the final visit. Secondary end points were the mean change from baseline to the final visit for SBP and DBP within and between racial groups; improvement in urinary protein excretion as measured by changes in the urinary albumin/creatinine ratio (UA/CR); and the effect of eplerenone in selected subpopulations, including women, obese patients, patients with SBP 160 mm Hg, elderly patients, and patients with microalbuminuria. Exploratory analyses assessed the rate of response to therapy and the relationships between BP changes and baseline active renin or aldosterone levels." Judgement comment: all primary study outcomes specified appear to have been reported. Secondary end points of improvement in urinary protein excretion as measured by changes in the urinary albumin/creatinine ratio and the effect of eplerenone in obese patients, elderly patients, and patients with microalbuminuria were not reported.
Other sources of bias	Unclear risk	Judgement comment: funding source unknown