| Methods |
Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out period = 1 to 4 weeks. Multicenter, conducted in USA |
| Participants |
Sitting DBP 95 to 114 mmHg. Mean age: HCTZ 25 mg = 53.2; placebo = 53.8 years. Males: HCTZ 25 mg = 53% and placebo = 55% |
| Interventions |
Benazepril 20 mg/d (N = 42), benazepril 5 mg, 10 mg or 20 mg/d + HCTZ 6.25 mg, 12.5 mg or 25 mg/d (all combined, N = 207), HCTZ 25 mg/d (N = 45) or placebo (N = 40)
Treatment duration = 6 weeks |
| Outcomes |
Change from the baseline in trough mean sitting DBP and SBP; pulse rate, serum potassium, body weight |
| Notes |
Study was adequately powered (73% and 87% power to detect a 5 and 6 mmHg difference in BP, respectively between any pair of treatments). The authors of the study did not state whether there were statistically significant differences across treatment groups in baseline demographics and characteristics. SD for BP data were not given (SEM only). Baseline BP was not given |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
"...patients were assigned to receive placebo or one of seven active treatment regimens according to a computer‐generated randomisation table." (line 4 under "Design" p.18) |
| Allocation concealment (selection bias) |
Unclear risk |
Not stated by study authors |
| Blinding (performance bias and detection bias)
All outcomes |
Low risk |
"The study was a 6‐week, randomised, double‐blind, placebo‐controlled, parallel‐group multicenter trial." (line 1 under "Design" p.18). "Study medication was provided as tablets of identical appearance and capsules of identical appearance..." |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
Efficacy analysis was based on an ITT technique
Exclusions: 73/407 (18%) of patients were excluded from the study during the single‐blind, placebo run‐in period prior to randomization, the majority of whom failed "to meet the Sitting DBP entry criterion."
Attrition: 33/334 (10%) of patients withdrew from the study for the following reasons: 12 ‐ lack of efficacy, 11 ‐ adverse events, 5 ‐ lost to follow‐up, 3 ‐ consent withdrawal and 2 ‐ protocol violations
WDAEs: 11/334 (3.3%) of patients (across all 8 treatment arms) withdrew due to adverse events (termed "adverse experiences"). This included 1 patient (1/45) receiving HCTZ 25 mg (1/45 = 2.2%) and 2 patients in the placebo group (2/40 = 5%); however the precise reasons were not given. Note: Data on total withdrawals were pooled (not presented as separate treatment arms) |
| Selective reporting (reporting bias) |
High risk |
Weight, heart rate, hematology and serum chemistry (except for potassium levels), urinalysis and ECG were measured, but not reported. BP data were provided as graphs only; variability in BP was expressed as SEM (standard error of the mean); baseline BP was not given. Variability in baseline patient demographics and characteristics was not given. Medical history of patients at baseline was not reported. SAEs: 4/334 (1.2%) across all treatment groups; authors did not account for all 4 patients, e.g. reasons were given for 2 patients only (hypotension and syncope). Note that data for SAEs were combined, not presented separately across all treatment groups. Total AEs were not reported; only AEs possibly or probably related to study drug were. Except for potassium levels, the following were measured but not reported on: weight, serum hematology, glucose, lipids, electrolytes, ECG and urinalysis. Mortalities were not mentioned. A post hoc subgroup analysis of black versus non‐black patients and patients < 65 and ≥ 65 years of age was performed and the results presented in 2 graphs; yet there was no mention of it in the methods section of the study |
| Industry sponsorship |
Unclear risk |
Sponsor was not reported |
