McGill 2001.
| Methods | Randomized, double‐blind, placebo‐controlled trial (parallel arms). 4 x 5 factorial design. Wash‐out period = 4 weeks Multicenter, conducted in USA | |
| Participants | Supine DBP 90 to 114 mmHg. Mean age 53 years. Males 60.3%. Baseline BP was 154.0/100.7 mmHg | |
| Interventions | Telmisartan 20 mg, 40 mg, 80 mg or 160 mg/d (all combined, N = 209), telmisartan 20 mg, 40 mg, 80 mg or 160 mg/d + HCTZ 6.25 mg, 12.5 mg or 25 mg/d (all combined, N = 414), HCTZ 6.25 mg, 12.5 mg or 25 mg/d (all combined, N = 121); or placebo (N = 74) Treatment duration = 8 weeks | |
| Outcomes | Change from baseline in mean trough supine and standing DBP and SBP; BP response rate; heart rate; vital signs, ECG, plasma renin activity and serum biochemistry | |
| Notes | A sample size calculation based on 75 patients in each key treatment group to detect a difference of at least 4 mmHg for each comparison (combination versus monotherapy) was provided at a power of 86%. The study authors stated that the baseline patient demographics and characteristic were comparable across treatment groups. Primary efficacy analysis did not include 6.25 and 25 mg doses of HCTZ. SD not used (SE was) Additional publications: McGill. Blood Pressure Monitoring 2001; 6 (Suppl 1): S3‐S13. Reported data were identical. Subgroup analysis of black patients included in Littlejohn III. Blood Pressure Monitoring 2001; 6 (Suppl 1): S15‐S21 and McGill. Clinical Cardiology 2001;24:66‐72 |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "This was a multicenter, randomised, double‐blind, placebo‐controlled, parallel‐group study...". "Randomization was according to enrolment order and a computer‐generated list..." (line 17 under "Study Design" p.836) |
| Allocation concealment (selection bias) | Unclear risk | Not stated by the study authors |
| Blinding (performance bias and detection bias) All outcomes | Unclear risk | "[An] 8‐week, double‐blind, double‐dummy comparison of telmisartan monotherapy, HCTZ monotherapy, telmisartan/HCTZ combination therapy and placebo." (line 5 under "Study Design" p.836). No further information was given |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | The primary efficacy analysis was based on an intention‐to‐treat (ITT) technique with the LOCF (last observation carried forward) Exclusions: 475/1293 (37%) patients were excluded from the study during the placebo run‐in period prior to randomization Attrition: 69/818 (8.4%) patients withdrew from the study for the following reasons: 24 patients for an "adverse event", 18 ‐ "lack of efficacy", 7 ‐ "noncompliance", 6 ‐ "lost to follow up", 6 ‐ "withdrawal of consent" and 8 ‐ "other reasons". Note that data were pooled, which made it impossible to ascertain from which treatment groups the patients originated. WDAEs: 24/818 (3%) patients withdrew due to adverse events. The study authors stated that 3 of the 24 patients were receiving HCTZ monotherapy or placebo, but it was not mentioned from which groups the patients originated. The precise reasons were not given |
| Selective reporting (reporting bias) | High risk | Vital signs, ECG and serum chloride, uric acid, BUN and glucose levels were measured but not reported at endpoint. Serum potassium levels and PRA (plasma renin activity) were expressed as mean change from baseline and did not include baseline measurements or variability. Variability in some of the baseline patient demographics and characteristics was not given; moreover, the data for the patients in the HCTZ groups were combined into one. Primary efficacy analysis did not include 6.25 and 25 mg doses of HCTZ. SE (standard error of the mean) was given for BP data, not SD. Results for standing DBP and SBP as well as heart rate were not reported. Trough‐peak ratios were not clearly stated for all treatment groups. Mortalities were not mentioned. SAEs: 1 patient in the HCTZ 6.25 mg group had a "uterine fibroid", 1 patient in the HCTZ 12.5 mg group had "syncope" and 1 patient on placebo had "oesophageal ulceration". Total AEs were reported in 50% of patients (all HCTZ groups combined) and in 42% of patients on placebo |
| Industry sponsorship | High risk | Supported by a restricted grant from Boehringer Ingelheim Pharmaceuticals, Inc |