Lacourciere 1994.
| Methods | Randomized, double‐blind, placebo‐controlled trial (parallel arms). 3 x 4 factorial design. Wash‐out period = 4 weeks. Conducted in Canada | |
| Participants | DBP 95 to 110 mmHg. Mean age not given. % of males not given. Baseline BP was 158/101 mmHg in both the treatment as well as the control group | |
| Interventions | Nebivolol 1 mg (N = 20), 5 (N = 20) or 10 mg/d (N = 20), nebivolol 1 mg, 5 mg or 10 mg/d + HCTZ 12.5 mg or 25 mg/d (N = 120, all combinations), HCTZ 12.5 mg (N = 20) or 25 mg/d (N = 20) or placebo (N = 20) Treatment duration = 12 weeks | |
| Outcomes | Change from the baseline in mean trough sitting SBP and DBP; heart rate, body weight and serum biochemistry (i.e. lipids profile). WDAE data available | |
| Notes | A sample size calculation was not provided. In addition to BP taken in the clinical setting, ambulatory BP, using a non‐invasive device was monitored to address "white‐coat hypertension". The latter was considered to be a research tool primarily and not yet clinically useful in the diagnosis and management of hypertension (see additional publication ‐ line 2 from top of p.143). After only 4 weeks of DB therapy (out of a total of 12 weeks), unresponsive patients who were withdrawn from the study were still considered fully evaluable in the efficacy analysis. (see additional publication ‐ line 19 from top of p.138) Study authors stated that sex, age, clinic and ambulatory BP and body mass index did not differ significantly across treatment groups. Metabolic data available as % change from baseline and not as actual values. Mortalities, SAEs and total AEs were not stated clearly Additional publication: Lacourciere Y et al. Am J Hypertens 1994;7:137‐45; ambulatory BP was measured using a 24 hour, non‐invasive BP device. Incidence of AEs (listed as WHO terms) was included in duplicate publication only |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "Patients...were randomly assigned to period B which consisted of a 12 week double‐blind treatment." (line 8 under "Study Design" p.284) |
| Allocation concealment (selection bias) | Unclear risk | Not stated by study authors |
| Blinding (performance bias and detection bias) All outcomes | Unclear risk | "Patients...were randomly assigned to period B which consisted of a 12 week double‐blind treatment." (line 8 under "Study Design" p.284) |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Primary efficacy analysis was based on an intention‐to‐treat (ITT) technique (see additional publication ‐ p.139)
Exclusions: 73/313 (23%) of patients were excluded from the study during the single‐blind placebo run‐in period prior to randomization (see duplicate publication ‐ p.139)
Attrition: 14/240 (5.8%) patients withdrew from the study. Reasons for withdrawals included, in the placebo group, 6 patients for inadequate response; in the HCTZ 12.5 mg group 1 patient was lost to follow‐up and in the HCTZ 25 mg group there were no withdrawals. The remaining patients who withdrew were receiving other (non‐thiazide) drugs (see additional publication ‐ p.139) WDAEs: 0/240 (0%) of patients withdrew due to an adverse event from the HCTZ 12.5 mg, HCTZ 25 mg or placebo groups (see additional publication ‐ p.139) |
| Selective reporting (reporting bias) | Unclear risk | Baseline BP was not given. Variability in mean change from baseline in BP was not given. Baseline patient demographics and characteristics were measured but not reported. Vital signs, laboratory values and ECG were measured but not reported. Total AEs were reported in the duplicate publication, if present, in at least 3 patients receiving active treatment which is equivalent to 3/40 = 7.5% of patients. This cut‐off percentage is much higher than the minimum of 3% chosen to present AE data in most other studies on use of thiazides for BP‐lowering. AEs were pooled using data from the HCTZ 12.5mg and HCTZ 25 mg treatment groups. Mortalities, SAEs and total AEs were not stated clearly |
| Industry sponsorship | High risk | Supported in part by a grant from Janssen Research Foundation and by Le Centre Hospitalier de l'Universite Lavale |