| Methods |
Randomized, double‐blind, placebo‐controlled trial. Wash‐out period = 4 weeks. Multicenter; conducted in France, Germany and Spain |
| Participants |
SBP/DBP 150 to <180/95 to < 110 mmHg or SBP/DBP 160 to < 180/< 90. Mean age 59 years. Males 50.7%. Baseline BP was 164/96.5 mmHg in the IND SR treatment group and 165/9 mmHg in the control group |
| Interventions |
Candesartan 8 mg/d (N = 435), amlodipine 5 mg/d (N = 445), indapamide SR 1.5 mg/d (N = 441), or placebo (N = 441) Treatment duration = 12 weeks |
| Outcomes |
Mean trough supine SBP and DBP; pulse pressure; response rate; automated ambulatory BP over a 24‐hour period; heart rate, body weight, hematology, serum biochemistry, hepatic and renal function |
| Notes |
A sample size calculation (based on unknown number of patients in each treatment group) was provided to detect a difference of 3 mmHg at 83% power. The study authors stated that the baseline patient demographics and characteristics (including their cardiovascular risk factors) were similar across all treatment groups (P value = NS). Biochemical data not given (except for serum potassium in IND SR group only). A subset of patients with isolated systolic hypertension was also evaluated, but not included in this review |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
"This was a multicenter, multinational, randomised, double‐blind, placebo‐controlled study with four parallel treatment arms." (line 1 under "Study Design" p.114). "...patients were randomised to receive either placebo, indapamide (1.5 mg) SR (sustained release), candesartan (8 mg), or amlodipine (5 mg)..." (line 4 under "Study Design" p.114). No further information given |
| Allocation concealment (selection bias) |
Unclear risk |
Not stated by study authors |
| Blinding (performance bias and detection bias)
All outcomes |
Unclear risk |
"This was a multicenter, multinational, randomised, double‐blind, placebo‐controlled study with four parallel treatment arms." (line 1 under "Study Design" p.114). No further information given |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
Primary efficacy analysis was based on the an intention‐to‐treat (ITT) technique
Exclusions: 608/2370 (25.7%) of patients were excluded from the study during the placebo run‐in period prior to randomization
Attrition: 14/441 (3.2%) patients from the IND SR group and 36/441 (8.2%) of patients on placebo, respectively, withdrew from the study. Reasons included (IND SR versus placebo) protocol violation: 3 versus 8; lack of efficacy: 1 versus 14; non‐medical reason: 2 versus 4 and adverse events: 8 versus 10
WDAEs: 8/441 (1.8%) of patients from the IND SR group and 10/441 (2.3%) of patients from the placebo group withdrew due to adverse events; the precise reasons were not given |
| Selective reporting (reporting bias) |
Unclear risk |
Weight, heart rate and laboratory parameters (including hematology, glucose levels, lipids profile and hepatic and renal function) were measured but not reported at baseline or endpoint. Mortalities: 1 patient from myocardial infarction in IND SR group; 0 in placebo group. SAEs: none. Total AEs were not reported |
| Industry sponsorship |
Unclear risk |
Sponsor not reported |
