Mersey 1993.
| Methods | Randomized, double‐blind, placebo‐controlled trial (parallel arms). Placebo run‐in period = 4 to 6 weeks Multicenter, conducted in USA | |
| Participants | Seated DBP 92 to 109 mmHg. Mean age (HCTZ 12.5 mg versus placebo): 52.1 versus 50.7 years. Males (HCTZ 12.5 mg versus placebo): 63% versus 59%. Baseline BP was 143.5/97.3 mmHg in the treatment group and 142.8/97.6 mmHg in the placebo group | |
| Interventions | Captopril 25 mg/d (N = 68), captopril 25 mg/d + HCTZ 12.5 mg/d (N = 69), captopril 50 mg/d + HCTZ 25 mg/d (N = 69), HCTZ 12.5 mg/d (N = 69) or placebo (N = 70) Trial duration = 8 weeks | |
| Outcomes | Change from baseline in mean trough seated, standing and supine DBP and SBP; BP response rate, heart rate; serum biochemistry (glucose, potassium, cholesterol, uric acid, BUN and creatinine levels) | |
| Notes | A sample size calculation was not provided. Study authors stated that baseline patient demographics and characteristics were similar across treatment groups. Variability in BP data was not given | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "Qualified patients were randomly assigned in a double‐blind manner to one of five treatment groups..." (line 12 under "Patients and Methods‐Patients and Treatment" p.503). 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 | "Qualified patients were randomly assigned in a double‐blind manner to one of five treatment groups..." (line 12 under "Patients and Methods‐Patients and Treatment" p.503) Comment: no further information was given |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | It is not known if the primary efficacy analysis was based on the per‐protocol or an intention‐to‐treat (ITT) population of patients Exclusions: 152/497 (31%) of patients were excluded from the study during the single‐blind placebo run‐in period prior to randomization Attrition: total withdrawals were reported separately based on study phase. 23/345 (7%) of patients withdrew from the study following randomization but prior to collection of efficacy data. The reasons were: 9 ‐ "loss to follow‐up", 6 ‐ "adverse drug experiences", 4 ‐ "patient request", 1 ‐ "concomitant illness", 1 ‐ "noncompliance", 1 ‐ "prohibited medication", 1 ‐ seated DBP < 92 mmHg after the lead‐in period". 26/345 (7.5%) more patients withdrew before the end of the study for the following reasons: 8 ‐ "adverse drug experiences", 3 ‐ "loss to follow‐up", 5 ‐ "specific requests", 3 ‐ "abnormal test results", 2 ‐ "prohibited medication", 2 ‐ "seated DBP ≥ 115 mmHg, 3 ‐ "other reasons". Therefore, total number of withdrawals during the study was 49/345 (14%) of patients. Note that the data were pooled, making it impossible to determine from which treatment group the patients originated WDAEs: the number of patients who withdrew due to any adverse events is not known; data were presented in terms of "adverse drug experiences" of which there were 14/345 (4%). Three more patients were withdrawn due to "abnormal lab test results"; if taken into account (presuming abnormal laboratory result = an adverse event), there were a total 17/345 (4.9%) WDAEs for the following reasons: in the HCTZ 12.5 mg group, 1 patient with "tightness and fluttering in chest" and 1 ‐ "proteinuria"; in the placebo group, 1 ‐ "chest pain". The remaining 14 patients with WDAEs were receiving non‐thiazide monotherapy or thiazide + non‐thiazide combo therapy (outside the scope of this systematic review). |
| Selective reporting (reporting bias) | Unclear risk | Hematology results were not shown; other biochemical data included the mean change and SE (standard error of the mean). Heart rate and change from baseline in standing and supine DBP and SBP were measured but actual values were not reported on at endpoint. Mean changes in seated DBP and SBP were represented in 2 graphs, however, variability in BP was not included in either. Variability was not given for baseline patient demographics and characteristics. There were no mortalities during the study. SAEs were not clearly stated. Total number of patients with any AEs were not reported, but a list of only the most frequently reported AEs was shown |
| Industry sponsorship | High risk | Funded by a grant from Bristol‐Myers Squibb Company |