| Methods |
Randomized, double‐blind, placebo‐controlled trial. 4 x 4 factorial design. Wash‐out period = 4 to 5 weeks. Multicenter, conducted in USA |
| Participants |
Supine, seated or standing DBP ≥ 95 mmHg (and seated DBP < 110 mmHg). Mean age 55 years. Males: 65%. Baseline seated BP was 151/100 mmHg |
| Interventions |
Irbesartan 37.5 mg, 100 mg or 300 mg/d (all combined, N = 126), irbesartan 37.5 mg, 100 mg or 300 mg/d + HCTZ 6.25 mg, 12.5 mg or 25 mg/d (all combined, N = 390), HCTZ 6.25 mg, 12.5 mg or 25 mg/d (all combined, N = 123) or placebo (N = 44)
Treatment duration = 8 weeks |
| Outcomes |
Mean change from baseline in trough DBP measured at 8 weeks; heart rate; serum biochemistry and ECG. WDAE given |
| Notes |
A sample size calculation based on 40 patients in each treatment group to detect a difference of 1.3 mmHg from the true mean in sitting DBP was provided at 95% power. The study authors stated that there were no statistically significant differences between treatment groups in baseline patient demographics and characteristics. Baseline BP was not given |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
"This randomised, double‐blind, placebo‐controlled study was conducted at 46 sites in the United States." (line 1 under "Materials and Methods‐Study Design" p.798). "To be eligible for randomisation, patients had to have a mean seated DBP at both weeks 3 and 4 between 95 and 100 mmHg and demonstrate good compliance." (line 5 under "Materials and Methods‐Study Design" p.798). 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 randomised, double‐blind, placebo‐controlled study was conducted at 46 sites in the United States." (line 1 under "Materials and Methods‐Study Design" p.798). "All patients were instructed to take three capsules (irbesartan or matching placebo) and one tablet (HCTZ or matching placebo) once daily between 6 AM and 10 AM for 8 weeks." (line 1 from top of p.798). No further information was given |
| Incomplete outcome data (attrition bias)
All outcomes |
Unclear risk |
Efficacy analysis was not mentioned (was it based on an intention‐to‐treat (ITT) or per‐protocol technique?). It was stated that 680 patients were included in the efficacy analysis
Exclusions: 443/1126 (39%) patients were excluded from the study during the single‐blind run‐in period prior to randomization. Specific reasons for each excluded patient were not given
Attrition: 52/683 (7.6%) patients withdrew from the study for the following reasons: 22 ‐ "adverse events", 9 ‐ "patient request", 10 ‐ "poor BP control", 4 ‐ "loss to follow‐up", 7 ‐ for various reasons, including "poor compliance", "use of prohibited medications" and "administrative issues". It is not known from which treatment groups these patients withdrew
WDAEs: 22/683 (3.2%) patients withdrew due to adverse events. WDAE data were expressed in percentages only and were pooled, not presented as separate according to each treatment group (i.e. HCTZ 6.25/12.5/25 mg = 4.1%; placebo = 4.5%). The most common reasons for the adverse events were given and were expressed in percentages, not in terms of numbers of patients |
| Selective reporting (reporting bias) |
High risk |
Baseline patient medical history was not given. Glucose, lipids and blood urea nitrogen levels; heart rate, ECG and urinalysis were measured but actual values were not reported on at the study's endpoint. Standing BP was measured, but not reported. Subgroup analysis of elderly versus young, black versus white and male versus female patients was reported, but not mentioned in the methods section of the study. Variability in the mean change of serum potassium and uric acid levels was not shown in the graphs at endpoint. Mortalities: none (0%). SAEs: 8/683 (1.2%) patients; specific reasons were not given. For the reporting of AEs, the HCTZ 6.25, 12.5 and 25 mg treatment groups were combined. Total AEs were not reported, only the "most common treatment‐emergent adverse events" were |
| Industry sponsorship |
High risk |
Sponsored by Bristol‐Myers Squibb Pharmaceutical Research Institute |
