Saruta 2007.
| Methods | Randomized, double‐blind, placebo‐controlled trial. Wash‐out period = 4 weeks. Multicenter; Japan, USA and Peru | |
| Participants | Sitting DBP 95 to 115 mmHg. Mean age 55 years. Males 59%. Baseline BP was 155/99.8 mmHg in the HCTZ 12.5 mg group and 153/100 mmHg in the placebo group | |
| Interventions | Losartan 50 mg/d (N = 160), losartan 25 mg or 50 mg/d + HCTZ 6.25 mg or 12.5 mg/d (all combined, N = 472), HCTZ 12.5 mg/d (N = 163) or placebo (N = 159) Trial duration = 8 weeks | |
| Outcomes | Change from the baseline in mean trough sitting, standing and supine DBP and SBP; heart rate, ECG, body weight, laboratory tests (including serum biochemistry and urinalysis). Subgroup analyses were performed (based on age and severity of hypertension) | |
| Notes | A sample size calculation was not provided. Study authors stated that there were no significant differences in the baseline patient demographics and characteristics across treatment groups. Patients were of Japanese descent. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "This randomised, placebo‐controlled, double‐blind, parallel‐group study..." (line 1 under "Study Procedures" p.730). "..those [patients] who continued to fulfil the eligibility criteria were randomised into 1 of 6 treatment arms..." (line 20 from bottom of p.731). 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 | Low risk | "If eligible, patients were given 5 placebo tablets matched to each of losartan 50 mg plus HCTZ 12.5 mg, losartan 50 mg plus HCTZ 6.25 mg, losartan 25 mg plus HCTZ 6.25 mg, losartan 50 mg and HCTZ 12.5 once daily for 4 weeks." (line 9 from top of p.731) |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | The primary efficacy analysis was based on a "full‐analysis set" with the LOCF (last observation carried forward) Exclusions: it was not stated whether any patients were excluded from the study during the placebo run‐in period prior to randomization Attrition: the total number of withdrawals was not given, except that there were 7 patients excluded from both efficacy and safety analyses in whom "previous medication for essential hypertension was discontinued or tapered before obtaining written consent" WDAEs: 4/163 (2.5%) patients receiving HCTZ12.5 and 1/159 (0.6%) patients receiving placebo withdrew due to adverse events; the specific reasons were not given |
| Selective reporting (reporting bias) | High risk | Trough standing BP, heart rate, ECG and body weight were measured, but not reported in the study. BP data at 2, 4 and 6 week time points were graphed. Results for the subgroup analyses comparing BP effects in terms of age and severity of hypertension were not shown. Serum biochemistry (except for uric acid, potassium and glucose levels) was not reported. Mortalities: none. SAEs: 9 patients (reasons were not given; and treatment groups were not specified). Total AEs were not clearly documented; they were reported separately as: "clinical" and "laboratory" AEs. By combining these 2 groups, it was then determined that 107/163 (65.6%) and 103/159 (64.8%) patients in the HCTZ and placebo groups, respectively, experienced AEs. A description of the 6 most commonly occurring "clinical" AEs in at least 2% of patients were reported. In addition, 5 of the most commonly occurring "laboratory" AEs in at least 4% of patients were reported |
| Industry sponsorship | High risk | Sponsored by Banyu Pharmaceutical Co. |