Brown 1990.
| Methods | Randomized, double‐blind, placebo‐controlled trial. Wash‐out period = 2 weeks. 2 centers: conducted in UK and France | |
| Participants | Supine DBP 95 to 115 mmHg. Patients 18 to 70 years. Mean age 58 years. Males 47.5%. Baseline supine and erect BP was 184/105 mmHg and 183/108 in the treatment group and 174/103 and 172/106 in the control group | |
| Interventions | Perindopril 4 mg/d (N = 10), perindopril 4 mg/d + HCTZ 25 mg/d (N = 10), HCTZ 25 mg (N = 10) or placebo (N = 10) Treatment duration = 4 weeks DB | |
| Outcomes | Change from baseline in trough mean supine and erect SBP and DBP; ECG, hematology and serum biochemistry; plasma renin and ACE activity, plasma aldosterone; perindopril/perindoprilat assay | |
| Notes | Sample size calculation was not provided. Small sample size of 10 patients per group. The study authors did not state whether there were statistically significant differences across treatment groups in the baseline patient demographics and characteristics. However, the reviewers determined the P value between HCTZ and placebo groups to be statistically significant (P value < 0.05) for supine SBP and DBP and for erect SBP. Baseline patient demographics such as age, sex ratio and body weight were not reported. Only standard error of the mean (SEM) of change in BP was given. Metabolic data were not reported | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "All 40 patients selected were then randomised to treatment and received either placebo (N = 10), perindopril 4 mg/day (N = 10), hydrochlorothiazide 25 mg/day (N = 10), or perindopril 4 mg/day and hydrochlorothiazide 25 mg/day (N = 10) for the next 4 weeks." (line 11 under "Study Design" p.328) Comment: no further information was given |
| Allocation concealment (selection bias) | Unclear risk | Not stated by study authors |
| Blinding (performance bias and detection bias) All outcomes | Low risk | "In order to ensure double‐blind conditions, each patient received once daily, two tablets which were identical in appearance." (line 15 under "Study Design" p.328). "The double‐blind code was then broken by a nurse who had no part in the clinical study and those patients taking perindopril (10 taking perindopril alone and 10 taking the combination of perindopril and hydrochlorothiazide) continued to take their treatment daily for a further 3 or 4 days." (line 16 from bottom of p.328) |
| 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 single‐blind placebo run‐in period prior to randomization Attrition: no patients withdrew from the study, however, there was one patient (1/10 = 10%) from the placebo group who was excluded from analysis because of "agitation which prevented BP measurements under stable conditions" WDAEs: not stated, but presumed to be none |
| Selective reporting (reporting bias) | High risk | Variability in baseline patient demographics and characteristics was not given. SEM (standard error of the mean) of BP was provided at baseline and SEM of change in BP at endpoint. Weight and heart rate were measured but not reported at the end of the study. Metabolic data were not given. Mortality, SAEs and total AEs were not documented. There was no systematic way of reporting AEs, only case by case reports |
| Industry sponsorship | Unclear risk | Sponsor not reported |