| Methods |
Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out period = 4 weeks. Conducted in USA |
| Participants |
DBP 100 to 115 mmHg. Mean age 50 years. Males 65%. Baseline BP not given |
| Interventions |
HCTZ 25 mg bid (N = 78), HCTZ 50 mg bid (N = 82) or placebo (N = 84)
Treatment duration = 4 weeks. This period was followed by 4 weeks of add‐on therapy with bevantolol 200 mg bid (therefore only the first 4 weeks were included in this review) |
| Outcomes |
Mean change from baseline in trough sitting DBP at 4 weeks; BP response rate; heart rate, body weight, hematology, urinalysis, serum biochemistry |
| Notes |
A sample size calculation was not provided. "At each clinic visit, four blood pressure readings were obtained at a time as close as possible to 12 hours after the previous dose." (line 5 from bottom on p.51). The study authors did not state whether baseline patient demographics and characteristics were statistically different or similar across treatment groups. No SD for BP or biochemical data. Biochemical data as % and not actual values. Mortalities, SAEs and total AEs were not reported. Total withdrawals and WDAEs were shown as combined data |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
"Subjects were then randomly allocated to one of three treatment groups and received either 50 mg/day of hydrochlorothiazide (25 mg twice daily), 100 mg/day of hydrochlorothiazide (50 mg twice daily), or placebo for four weeks." (line 4 under "Methods" p.51). 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 |
"...patients entering the double‐blind phase..." (line 4 from bottom of p.51). No further information given |
| Incomplete outcome data (attrition bias)
All outcomes |
Unclear risk |
Primary efficacy analysis whether based on an intention‐to‐treat (ITT) or per‐protocol technique is not reported
Exclusions: it is not known whether any patients were excluded from the study during the placebo run‐in period prior to randomization
Attrition: 16/244 (6.6%) patients withdrew from the monotherapy phase of the study. Reasons for withdrawals were not given
WDAEs: 7/244 (3%) patients withdrew due to adverse events; the precise reasons were not given. Data on total withdrawals and WDAEs (above) were pooled rather than shown separately for each treatment group |
| Selective reporting (reporting bias) |
High risk |
Weight, general physical condition, hematology and urinalysis results were measured but not reported at baseline or endpoint. Serum biochemical levels including lipids were expressed as percentages rather than as mean ± SD changes from baseline. Variability in BP and heart rate data were not given. Mortalities, SAEs and total AEs were not documented |
| Industry sponsorship |
Unclear risk |
Sponsor not reported |
