| Methods |
Randomized, double‐blind, placebo‐controlled trial (parallel arms). 4 x 3 factorial design. Wash‐out period = 4 weeks. Multicenter, USA |
| Participants |
Mean age 54 years. 60% males. Sitting DBP 95 to 115 mmHg. Baseline DBP = 100.3 mmHg |
| Interventions |
Cilazapril 0.5 mg, 5 mg or 10 mg/d (all combined, N = 288), cilazapril 0.5 mg, 5 mg or 10 mg/d + HCTZ 12.5 mg or 25 mg/d (all combined, N = 579), HCTZ 12.5 mg or 25 mg/d (all combined, N = 198), or placebo (N = 97)
Trial duration = 4 weeks |
| Outcomes |
Change from baseline in trough mean sitting DBP; response rate; peak BP and trough:peak ratios; heart rate, ECG, body weight, hematology, serum biochemistry, urinalysis |
| Notes |
A sample size calculation was not provided. Study authors stated that there were no "overt differences" (P value = NS) in baseline patient demographics and characteristics across treatment groups. Total AEs were not reported |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
"This double‐blind, randomised, placebo‐controlled, multicenter study compared the effects of three doses of the ACE inhibitor, cilazapril (CLZ) and two doses of HCTZ, alone and in combination." (line 21 from top of p.312). "...patients [were] randomly assigned in blocks of 12 to one of 12 treatment groups." (line 1 under "Materials and Methods‐Study Design" p.312) |
| Allocation concealment (selection bias) |
Unclear risk |
Not stated by study authors |
| Blinding (performance bias and detection bias)
All outcomes |
Unclear risk |
"...period II (active treatment) consisted of a 4‐week, double‐blind, placebo‐controlled comparison of three doses of CLZ and two doses of HCTZ, alone and in combination." (line 4 from top of p.312). No further information was given |
| Incomplete outcome data (attrition bias)
All outcomes |
Unclear risk |
The primary efficacy analysis was based on an intention‐to‐treat (ITT) technique
Exclusions: 856/2018 (42%) of patients were excluded from the study during the placebo run‐in period prior to randomization
Attrition: 74/1088 (6.8%) of patients withdrew from the study, 13/198 (6.6%) from the HCTZ 12.5 and 25 mg groups combined and 11/97 (11%) from the placebo group (the other 50 patients were receiving non‐thiazides). The reasons for withdrawing were given, but with the data pooled, it was not possible to ascertain from which treatment groups the patients originated
WDAEs: 33/1088 (3%) of patients withdrew due to adverse events, 5 (2.5%) from the HCTZ 12.5 and 25 mg group and 3 (3%) from the placebo group; the other 25 patients were receiving non‐thiazides. No specific reasons were given |
| Selective reporting (reporting bias) |
High risk |
Heart rate, body weight, ECG and laboratory results including serum biochemistry, hematology, lipids and urinalysis were measured but actual values were not reported on at either baseline or endpoint. BP data were expressed in terms of mean ± SEM (standard error of the mean). Mortalities: 1 death from the CLZ + HCTZ combo therapy group. None from HCTZ or placebo groups. SAEs: 30 patients in total, including 6 from the HCTZ 12.5 and 25 mg groups, combined. Total AEs were not reported. Only AEs related in some way to the medication were reported |
| Industry sponsorship |
Unclear risk |
Sponsor not reported |
