| Methods |
Randomized, double‐blind, placebo‐controlled dose‐ranging trial (parallel arms). Wash‐out period = 4 weeks. Multicenter, conducted in Scandinavia (Finland, Sweden, Norway and Denmark) |
| Participants |
DBP 95 to 115 mmHg. Mean age 48.5 years. Males 39.6%. Baseline BP was 152.8/99.3 mmHg in the treatment group and 152.5/99.8 mmHg in the control group |
| Interventions |
HCTZ 3 mg (N = 22), 6 mg (N = 22), 12.5 mg (N = 22), 25 mg/d (N = 23) or placebo (N = 22)
Treatment duration = 6 weeks |
| Outcomes |
Change from the baseline in mean standing and supine DBP and SBP; heart rate; serum biochemistry, hematology, urinalysis, ECG; plasma renin activity |
| Notes |
A sample size calculation was not provided. Baseline patient characteristics did not include medical history. Study authors stated that baseline patient characteristics were similar across treatment groups. Standing BP change from baseline available but no SD given. Supine BP with SD given. Mortality data were not reported |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
"Patients...were randomly allocated on a double‐blind basis to receive placebo or hydrochlorothiazide (HCTZ) at a dose of 3, 6, 12.5, or 25 mg once daily." (line 1 under "Study Design" p.231). "Random allocation was performed using randomisation tables." (line 5 under "Study Design" p.231) |
| Allocation concealment (selection bias) |
Unclear risk |
Not stated by study authors |
| Blinding (performance bias and detection bias)
All outcomes |
Low risk |
"Patients...were randomly allocated on a double‐blind basis to receive placebo or hydrochlorothiazide..." (line 1 under "Study Design" p.231) "Placebo and active tablets were identical in appearance and taste." (line 6 under "Study Design" p.231) |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
Not known whether efficacy analysis was based on an intention‐to‐treat (ITT) or per‐protocol technique Exclusions: no patients were excluded from the study during the placebo run‐in period prior to randomization
Attrition: 3/111 (3%) patients withdrew from the study for the following reasons: 1 ‐ headache, palpitation and vertigo (12.5 mg HCTZ group), 1 ‐ palpitation (25 mg HCTZ group) and 1 ‐ lost to follow‐up (group not specified)
WDAEs: HCTZ 12.5 mg group: 1 patient due to headache, palpitation and vertigo; HCTZ 25 mg group: 1 patient due to palpitation |
| Selective reporting (reporting bias) |
High risk |
ECG, heart rate, urinalysis, serum creatinine levels, hemoglobin, hematocrit, WBC and platelets were measured but their values (mean ± SD) not reported at baseline or endpoint. Variability was not given for baseline patient characteristics. Standing BP was not reported at baseline and its variability not reported at endpoint. Mortalities were not documented. SAEs: no patients had what study authors reported to be "serious clinical adverse experiences". Total AEs: in HCTZ 3, 6, 12.5 and 25 mg/d and placebo groups there were 2 (9%), 4 (18%), 3 (13.6%), 4 (17%) and 1 (4.5%) patients who experienced AEs |
| Industry sponsorship |
Unclear risk |
Sponsor not reported |
