| Methods |
Randomized, double‐blind, placebo‐controlled trial. Factorial design. Wash‐out period = 2 to 6 weeks. Multicenter, conducted in Germany |
| Participants |
DBP 95 to 110 mmHg. Mean age 55.1 years |
| Interventions |
Candesartan 2 mg, 4 mg, 8 mg or 16 mg/d, candesartan 2 mg, 4 mg, 8 mg or 16 mg/d + HCTZ 12.5 mg or 25 mg/d, HCTZ 12.5 mg (N = 60) and 25 mg/d (N = 123) or placebo (N = 119). N = 1096 randomized
Trial duration = 8 weeks |
| Outcomes |
Change from the baseline in mean sitting DBP and SBP (measured using an automated BP device); BP response rate; heart rate, ECG, urinalysis and blood tests |
| Notes |
A sample size calculation was not provided. Study authors stated that baseline patient demographics and characteristics, including medical history and previous treatment with antihypertensives were "well matched" across treatment groups. Baseline BP was not given. Variability in BP not given. Mortalities, SAEs and total AEs were not given. Biochemical data measured but not reported |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
"...1096 patients were randomised to once‐daily oral treatment with candesartan cilexetil 2, 4, 8, or 16 mg, HCTZ 12.5 or 25 mg, combination therapy with both agents at these respective doses, or placebo." (line 7 under "Patients and Methods" p.S67). No further information was given |
| Allocation concealment (selection bias) |
Unclear risk |
Not stated by the study authors |
| Blinding (performance bias and detection bias)
All outcomes |
Unclear risk |
"[Patients] were recruited to this double‐blind, factorial design study..." (line 3 under "Patients and Methods" p.S67). No further information was given |
| Incomplete outcome data (attrition bias)
All outcomes |
High risk |
Primary efficacy analysis was based on an intention‐to‐treat (ITT) technique
Exclusions: 210/1306 (16%) of patients were excluded from the study during the wash‐out and placebo run‐in periods prior to randomization. The specific reasons were not given
Attrition: the number of patients who withdrew from the study was not given nor how their data were analyzed has been provided
WDAEs: not clearly documented. It was stated that "2.4% of patients withdrew from the study due to adverse occurrences." (line 7 from top of p.S68), but no further information was given |
| Selective reporting (reporting bias) |
High risk |
Heart rate, ECG, serum chemistry and urinalysis were measured, but not given. Except for mean age, all other baseline patient demographics and characteristics were undocumented. Variability was not included in BP data. Baseline BP was not reported. Mortalities, SAEs and total AEs were not given |
| Industry sponsorship |
Unclear risk |
Sponsor not reported |
