Yodfat 1994.
| Methods | Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out period = 4 weeks. Multicenter; Israel and Italy | |
| Participants | Sitting DBP > 100 mmHg. Mean age 53 years. 65% males. Baseline BP was not given | |
| Interventions | Cilazapril 2.5 mg or 5 mg/d (all combined, N = 94), cilazapril 1.25 mg, 2.5 mg or 5 mg/d + HCTZ 6.25 mg, 12.5 mg or 25 mg/d (all combined, N = 142), HCTZ 12.5 mg or 25 mg/d (all combined, N = 95), or placebo (N = 46) Trial duration = 8 weeks | |
| Outcomes | Change from baseline in mean trough sitting DBP and SBP (at weeks 2, 6 and 8); peak BP; response rate; pulse rate, ECG, hematology, urinalysis and serum biochemistry | |
| Notes | A sample size calculation was not provided. The study authors did not state whether there were statistically significant differences between the treatment groups in terms of the baseline patient demographics and characteristics. We determined there to be no statistically significant differences (P value = NS) in mean age, body weight, height or gender. Mortalities and total AEs not reported | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "This report presents the results of a parallel‐group, placebo‐controlled, randomised study..." (line 12 from top of p.118). "All patients who entered period II were randomly assigned to a double‐blind, fixed dose, active treatment period of eight weeks." (line 6 (right column) from top of p.118). 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 | "All patients who entered period II were randomly assigned to a double‐blind, fixed dose, active treatment period of eight weeks." (line 6 (right column) from top of p.118). No further information was given |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | The primary efficacy analysis was based on an intention‐to‐treat (ITT) technique Exclusions: 161/538 (30%) of patients were excluded from the study during the placebo run‐in period prior to randomization Attrition: 14/377 (3.7%) of patients withdrew from the study; the specific reasons and the treatment groups from which the patients originated were not given WDAEs: 7/377 (1.9%) of patients withdrew due to "adverse reactions", including 1 from the HCTZ group, however it is not known which dosage, 12.5 or 25 mg, the patient was receiving (the other 6 patients were receiving cilazapril + HCTZ combo therapy). The specific reasons were not given |
| Selective reporting (reporting bias) | High risk | Heart rate, body weight, ECG, hematology, serum biochemistry and urinalysis results were measured but actual values were not reported at the study's endpoint. Data for the HCTZ 12.5 mg and 25 mg treatment groups were pooled. BP measurements were not shown beyond week 4 of the 8‐week study. All DBP data were in graph form only and variability in the mean was not given. SBP was measured, but not shown Baseline patient demographics and characteristics did not include medical history. Mortalities: not given. SAEs: 3 patients receiving HCTZ (12.5 and 25 mg groups combined) for "aggravated hypertension", "AV‐block" and "angina". Total AEs were not reported; treatment‐related AEs were. Only the 5 most commonly occurring AEs in patients receiving combination therapy (i.e. cilazapril + HCTZ) were listed |
| Industry sponsorship | Unclear risk | Sponsor not reported |
ACE: angiotensin‐converting enzyme AE: adverse effect BDFZ: bendrofluazide bid: twice a day BMI: body mass index BP: blood pressure BUN: blood urea nitrogen CI: confidence interval CLZ: cilazapril CTD: chlorthalidone d: day DB: double‐blind DBP: diastolic blood pressure ECG: electrocardiography ER: extended release GI: gastrointestinal HCTZ: hydrochlorothiazide HDL: high‐density lipoprotein HR: heart rate IND: indapamide IR: immediate release ITT: intention‐to‐treat LDL: low‐density lipoprotein LOCF: last observation carried forward NS: non‐significant PLB: placebo PRA: plasma renin activity q12h: every 12 hours RBC: red blood cells SAE: serious adverse event SBP: systolic blood pressure SD: standard deviation SE: standard error SEM: standard error of the mean SR: sustained release VAL: valsartan WBC: white blood cells WDAE: withdrawal due to adverse events XR: extended release