Pool 2007.
| Methods | Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out period = 2 weeks, followed by a 2 to 4‐week single‐blind, placebo run‐in. Multicenter, conducted in USA and Canada | |
| Participants | Mean age, all HCTZ groups combined (˜53 years); placebo (52 years). Males, all HCTZ groups (62%); placebo (49%). Body mass index, HCTZ group (32); placebo (31). Sitting DBP 90 to < 110 mmHg after wash‐out. SBP 151.2 + 12.7 mmHg and DBP 99.1 + 3.9 mmHg in HCTZ group and SBP = 150.4 + 12.7 mmHg and DBP = 99.1 + 3.7 in placebo group | |
| Interventions | Valsartan 160 mg (N = 166) or 320 mg/d (N = 170), valsartan 160 mg or 320 mg/d + HCTZ 12.5 mg or 25 mg/d (all combined, N = 505), HCTZ 12.5 mg (N = 169), 25 mg/d (N = 167) or placebo (N = 169) Trial duration = 8 weeks | |
| Outcomes | Change from the baseline to endpoint in mean trough seated DBP and SBP; response rate; pulse rate; hematology, serum biochemistry | |
| Notes | A sample size calculation was provided (number of patients per treatment group not specified) to detect a difference of 3 mmHg in seated DBP (SD ± 8 mmHg) at 90% power. Patients in the study were overweight/obese with an average BMI of 31 to 32. Study authors stated that except for gender (P value = 0.03), the baseline patient demographics and characteristics, including BP were not significantly different across treatment groups (P value = NS). SE (standard error of mean) was given for BP, not SD. Biochemical data incomplete. SAEs and total AEs were not reported |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "...this study was an 8‐week, multicenter, randomised, double‐blind, placebo‐controlled, parallel‐group trial..." (line 1 under "Patients and Methods" p.62). "...patients who met the study inclusion criteria were randomised (visit 3, week 0) in a double‐blind fashion to 1 of 8 treatment groups: VAL monotherapy at a dose of 160 or 320 mg; HCTZ monotherapy at 12.5 or 25 mg; VAL/HCTZ 160/12.5, 320/12.5, or 320/25 mg; or placebo." (line 7 under "Study Design" p.62). 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 study was an 8‐week, multicenter, randomised, double‐blind, placebo‐controlled, parallel‐group trial..." (line 1 under "Patients and Methods" p.62). No further detail provided |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Primary efficacy analysis was based on an intention‐to‐treat (ITT) technique with the LOCF (last observation carried forward) Exclusions: the number of patients excluded from the study during the placebo run‐in period prior to randomization was not given Attrition: 185/1346 (14%) of patients withdrew from the study. Data on total withdrawals was incomplete. Study authors selectively reported the specific reasons i.e. "the most common reasons for discontinuations were unsatisfactory therapeutic effect (4.4%), AEs (3.1%) and withdrawn consent (2.2%)." (see line 8 under "Results" p.65). Note that data were pooled from all treatment groups, therefore it could not be determined from which groups the patients originated WDAEs: 3.1% of patients withdrew due to adverse events. The specific reasons were not given and no details were given as to which treatment groups the patients originated. The study authors were selective in their reporting of WDAEs, i.e. in terms of a range of percentages only |
| Selective reporting (reporting bias) | High risk | Pulse rate, hematology, serum biochemistry (except for potassium levels) were measured, but not reported. BP data included SE (standard error of the mean), not SD. Variability in BP data and in serum potassium levels were not reported. Mortalities: 1 patient receiving valsartan 320 mg died (reason was not given). No patients from HCTZ or placebo groups died. SAEs: not given. Total AEs were not reported; study authors were selective in their reporting of AEs, i.e. in terms of a range of percentages and a listing of the 3 most commonly occurring AEs only |
| Industry sponsorship | High risk | Funded by Novartis Pharmaceuticals Corporation |