Papademetriou 2000.
| Methods | Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out period = 1 week wash‐out + single‐blind placebo run‐in of 4 to 5 weeks. Multicenter, USA | |
| Participants | DBP 95 to 114 mmHg. Mean age 52 years. Males 56%; blacks 21%. Average weight: males, 213 lb and females, 184 lb Baseline BP was 152/100 |
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| Interventions | Candesartan 32 mg/d (N = 73), candesartan 32 mg/d + HCTZ 12.5 mg/d (N = 64), HCTZ 12.5 mg/d (N = 72) or placebo (N = 66) Trial duration = 8 weeks | |
| Outcomes | Change from baseline in trough sitting and standing DBP and SBP (at weeks 2, 4 and 8); peak SBP and DBP; BP response rate; heart rate; serum potassium levels and other laboratory parameters (not specified). Subgroup analyses were performed (black versus non‐blacks) | |
| Notes | A sample size calculation was not provided. The study included patients who had an average body weight of 213 and 184 lb. for men and women. Excess weight and obesity is associated with other diseases, which could have biased the BP and safety results. The medical history of patients at baseline was not included in the study. It was not stated whether there were statistically significant differences in baseline patient demographics and characteristics across treatment groups. BP data contained SEM (standard error of the mean), not SD. Total withdrawals and total AEs not given | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "[Patients] were randomly assigned to one of the following 4 groups: placebo, hydrochlorothiazide (HCTZ) 12.5 mg daily, candesartan 32 mg daily, or a combination of candesartan and HCTZ." (line 1 from top of p.373) |
| 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, double‐blind, placebo‐controlled study of patients with essential hypertension." (line 1 under "Methods" p.373). "The duration of the double‐blind treatment phase was 8 weeks." (line 3 from top of p.373) |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Primary efficacy analysis was based on an intention‐to‐treat (ITT) technique with the LOCF (last observation carried forward) Exclusions: not given Attrition: not given WDAEs: a total of 10/275 (3.6%) patients withdrew due to adverse events (5 from non‐thiazide treatment groups), 3/72 (4.2%) patients receiving HCTZ 12.5 mg and 2/66 (3%) patients on placebo. The precise reasons were not given |
| Selective reporting (reporting bias) | High risk | Body weight (except at baseline), heart rate and serum chemistry (except for potassium) were measured but actual values were not given. ECG was not reported. Mortalities: none. SAEs: 1 patient in the HCTZ group and 4 patients in the placebo group. Total AEs were not reported. The most commonly reported AEs were upper respiratory infections and headache (treatment groups not specified) |
| Industry sponsorship | Unclear risk | Sponsor not reported |