| Methods |
Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out period = 4 weeks. Multicenter, conducted in USA |
| Participants |
DBP 100 to 114 mmHg. Mean age 53.5 years. Males 58.2%. Baseline BP was 155/103 mmHg in both the treatment groups as well as the control group |
| Interventions |
Lisinopril 10 mg/d (N = 85), lisinopril 10 mg/d + HCTZ 12.5 mg or 25 mg/d (all combined, N = 168), HCTZ 12.5 mg (N = 87), or 25 mg/d (N = 84), or placebo (N = 81)
Trial duration = 8 weeks |
| Outcomes |
Change from the baseline in trough mean sitting and standing SBP and DBP; ECG, heart rate, serum biochemistry, hematology and urinalysis |
| Notes |
Sample size calculation was provided ‐ study had a power of 95% to detect a change in sitting DBP of 5 mmHg between treatment groups. The study authors stated that "there were no significant differences between the various treatment groups" in baseline patient demographics and characteristics (i.e. age, body weight, BP and heart rate). BP data in graphical form only. Mean change from the placebo group with 95% CIs available. WDAEs, mortalities, SAEs and total AEs not reported |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
"...patients...were randomised into the double‐blind phase of the study..." (line 21 under "Patients and Methods" p.738). No further information was given |
| 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, parallel, placebo‐controlled study." (line 1 under "Patients and Methods" p.738). No further information was given |
| Incomplete outcome data (attrition bias)
All outcomes |
Unclear risk |
Efficacy analysis was based on an ITT technique
Exclusions: 244/749 (33%) patients were excluded from study after the 4‐week single‐blind, placebo run‐in period prior to randomization for "having BP lower than those required for inclusion."
Attrition: 38/505 (7.5%) patients withdrew from the study, 8 from the HCTZ 12.5 mg group, 7 from the HCTZ 25 mg group and 10 from the placebo group. The reasons for withdrawing were not given
WDAEs: not given |
| Selective reporting (reporting bias) |
High risk |
Gender, medical history and variability (i.e. SD) in baseline patient demographics and characteristics were not given. BP data were graphed only and variability was expressed as SEM (standard error of the mean), not SD. Blood cell counts and ECG were measured but not reported; weight and heart rate were measured and reported at baseline, but not at endpoint. Mortalities, SAEs and total AEs were not reported. Only 5 of the most commonly reported adverse of events were given. Results from a subgroup analysis of BP‐lowering effects in black and elderly patients were shown but the analysis was not mentioned a priori (i.e. was not included in the methods section of the study); refer to Table 3 p.740 |
| Industry sponsorship |
High risk |
Supported by a grant from ICI Pharmaceuticals Group |
