| Methods |
Randomized, double‐blind, placebo‐controlled trial. Modified 4 x 4 factorial design. Wash‐out period = 4 to 5 weeks. Multicenter, USA |
| Participants |
Mean age 51.5 years. Males 61%. Body weight: 90.5; body mass index: 30.6. Seated DBP 95 to 110 mmHg. Seated SBP 149.5 + 15.7 mmHg and seated DBP 100.1 + 4.0 mmHg |
| Interventions |
Fosinopril 2.5 mg (N = 33), 10 mg (N = 30) or 40 mg/d (N = 32), fosinopril 2.5 mg, 10 mg, 20 mg or 40 mg/d + HCTZ 5 mg, 12.5 mg or 37.5 mg/d (all combined, N = 325), HCTZ 5 mg (N = 32), 12.5 mg (N = 32) or 37.5 mg/d (N = 32), or placebo (N = 32)
Trial duration = 8 weeks |
| Outcomes |
Change from the baseline in mean trough sitting, standing and supine DBP and SBP; response rate; heart rate; hematology, urinalysis, serum biochemistry |
| Notes |
A sample size calculation was not provided. Patients in the study were overweight/obese with an average BMI of 31. Study authors stated that except for seated DBP, the baseline patient demographics and characteristics were not significantly different across treatment groups (P value = NS). Variability in BP not given. Biochemical data measured but not reported |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
"The...study was a modified 4 x 4 factorial, randomised, double‐blind, parallel group trial of 17 different doses of the combination of Fos and HCTZ, comparing each of the combinations with the individual components and placebo." (line 1 under "Study Design" p.118). No further information was given |
| Allocation concealment (selection bias) |
Unclear risk |
Not stated by the study authors |
| Blinding (performance bias and detection bias)
All outcomes |
Unclear risk |
"The...study was a modified 4 x 4 factorial, randomised, double‐blind, parallel group trial..." (line 1 under "Study Design" p.118). "Subjects took their first randomised, double‐blind medication under supervision in the clinic..." (line 20 under "Study Design" p.118). No further information was given |
| Incomplete outcome data (attrition bias)
All outcomes |
Unclear risk |
Primary efficacy analysis was based on both an intention‐to‐treat (ITT) and per‐protocol technique, however the study included data from the ITT population only
Exclusions: 159/709 (22.4%) of patients were excluded from the study during the placebo run‐in period prior to randomization
Attrition: 45/550 (8%) of patients withdrew from the study; the specific reasons were not given. Data were pooled from all treatment groups, therefore it could not be determined from which groups the patients originated
WDAEs: 19/550 (3.5%) of patients withdrew due to adverse events; this included 1% of patients from the HCTZ 5, 12.5 and 37.5 mg groups combined and 3.1% of patients from the placebo group. The specific reasons were not given |
| Selective reporting (reporting bias) |
High risk |
Parameters for biochemistry, hematology and urinalysis were measured, but not reported on. Variability in BP data was not reported. Serum biochemistry, hematology and urinalysis results were measured but not reported. Mortalities and total AEs were not documented. There were 5 SAEs; specific reasons were not given |
| Industry sponsorship |
High risk |
Supported by grant from Bristol‐Myers Squibb Company |
