Chrysant 2004.
| Methods | Randomized, double‐blind, placebo‐controlled trial (parallel arms). 3 x 4 factorial design. Wash‐out period = 4 weeks. Multicenter, conducted in USA | |
| Participants | Sitting DBP ≥ 100 and ≤ 115 mmHg. Mean age: HCTZ 12.5 mg = 54.1; HCTZ 25 mg = 54.7; placebo = 54.0 years. Males: HCTZ 12.5 mg = 55.6%; HCTZ 25 mg = 49%; placebo = 64.3%. Baseline mean sitting SBP/DBP ranged from 151.9 to 156.6 mmHg/102.6 to 104.4 mmHg | |
| Interventions | Olmesartan medoxomil 10 mg (N = 39), 20 mg (N = 41) or 40 mg/d (N = 45), olmesartan medoxomil 10 mg, 20 mg or 40 mg/d + HCTZ 12.5 mg or 25 mg/d (all combined, N = 247), HCTZ 12.5 mg (N = 45) or 25 mg/d (N = 43), or placebo (N = 42) Trial duration = 8 weeks | |
| Outcomes | Change from baseline in trough mean sitting and standing DBP and SBP; BP response rate; heart rate, serum biochemistry, hematology and urinalysis | |
| Notes | Sample size calculation was based on change (magnitude not given) from baseline in sitting DBP at week 8 (90% power). SD for BP data were not given. Biochemical data not given. Mortalities 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 was a randomised, double‐blind, factorial design study..." (line 1 under "Methods‐Study Population" p.253) "...eligible patients (N = 502) were randomised to one of 12 treatment groups..." (line 2 under "Methods‐Study Design" p.253). No further information given |
| Allocation concealment (selection bias) | Unclear risk | Not stated by the study authors |
| Blinding (performance bias and detection bias) All outcomes | Unclear risk | "...eligible patients (N = 502) were randomised to one of 12 treatment groups for 8 weeks of double‐blind treatment with placebo, olmesartan medoxomil monotherapy, HCTZ monotherapy, or olmesartan medoxomil/HCTZ combination therapy..." (line 2 under "Methods‐Study Design" p.253). No further information given |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Efficacy analysis was based on an ITT technique with the LOCF (last observation carried forward) Exclusions: 863 patients were screened and 750 of these were enrolled. 248/750 (33%) of patients were excluded from the study during the single‐blind, placebo run‐in period prior to randomization. The reasons for these exclusions were not given Attrition: 51/502 (10%) patients withdrew from the study; the reasons for withdrawing were not given. Data were combined, not presented separately for each treatment group WDAEs: the study reported WDAEs only for those patients receiving one or both of the study drugs (not placebo), which was about 2%. The precise reasons for these withdrawals and from which treatment group the patients originated were not given |
| Selective reporting (reporting bias) | Unclear risk | Baseline and endpoint body weight, heart rate, height, hematology, serum chemistry and urinalysis were measured but actual values were not reported; any changes at endpoint were noted qualitatively. Variability in BP data was not given. Variability in baseline patient demographics and characteristics was also not given. Baseline standing BP was measured, but not reported. Medical history was measured but not reported with the baseline patient demographics and characteristics. Mortalities were not mentioned SAEs: 1 patient in the placebo group with "unstable angina"; no other SAEs were reported. Total AEs were not reported; only the most commonly reported AEs were mentioned |
| Industry sponsorship | High risk | Supported by a grant from Sankyo Pharma Inc. |