Kayanakis 1987.
| Methods | Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out period = 2 weeks. Multicenter, conducted in France | |
| Participants | SBP 160 to 200 mmHg. DBP 95 to 120 mmHg. Mean age 53.5 years. Males 54.8%. Baseline BP was 176.6/103.2 mmHg in the treatment group and 172/102.5 mmHg in the control group | |
| Interventions | Captopril 50 mg/d (N = 43), captopril 50 mg/d + HCTZ 25 mg/d (N = 45), HCTZ 25 mg daily (N = 43) or placebo (N = 86) Treatment duration = 8 weeks | |
| Outcomes | Trough standing and supine SBP and DBP; response rate; heart rate, hematology, urinalysis, body weight, serum biochemistry | |
| Notes | A sample size calculation was not provided. Although the study's focus was on mild to moderate essential hypertension, patients with relatively severe BP as high as 200/120 mmHg were included (line 2 under "Patients" p.89S). Study authors stated that the baseline patient demographics and characteristics were similar across treatment groups. BP and SD in graph form only (Fig. 1 and 2 p.91S). Biochemical data restricted to serum potassium from patients in the HCTZ group. Mortalities and SAEs were not reported | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "The study was divided into two phases: a placebo run‐in period of 2 week's duration and an active treatment period of 8 weeks duration when the patients were randomised in four groups: captopril 50 mg, hydrochlorothiazide 25 mg combination once daily, captopril 50 mg alone once daily, hydrochlorothiazide 25 mg alone once daily or placebo once daily." (line 1 under "Methods‐Trial Design" p.90S). No further information given |
| Allocation concealment (selection bias) | Unclear risk | Not stated by the study authors |
| Blinding (performance bias and detection bias) All outcomes | Unclear risk | "A double‐blind design was used for the 8 weeks of active treatment." (line 9 under "Methods‐Trial Design" p.90S). Comment: no further information given |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Not known whether efficacy analysis was based on an intention‐to‐treat (ITT) or per‐protocol technique Exclusions: 4/221 (1.8%) of patients were excluded from the study during the placebo run‐in period prior to randomization (line 1 under "Results‐Patient Population" p.90S) Attrition: 2/43 (4.7%) and 3/86 (3.5%) of patients from the HCTZ and placebo groups, respectively, withdrew from the study. Reasons for withdrawals included (HCTZ versus PLB): 1 ‐ inefficacy and 1 ‐ lost to follow‐up versus 2 ‐ inefficacy and 1 ‐ lost to follow‐up WDAEs: 0/211 (0%) of patients withdrew due to adverse events |
| Selective reporting (reporting bias) | Unclear risk | Baseline patient characteristics did not include medical history. Standing BP, heart rate and weight were measured but not reported at the end of the study. BP data were graphed only. Except for potassium levels, changes in mean ± SD for serum biochemistry, hematology and urinalysis were not shown at endpoint. Mortalities and SAEs were not clearly documented. Total AEs: 9/43 (20%) patients in HCTZ group and 14/86 (16%) patients on placebo. The most commonly occurring AE, GI upset was experienced by 8 patients receiving HCTZ and 10 patients receiving placebo |
| Industry sponsorship | Unclear risk | Sponsor not reported |