| Methods |
Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out period = 4 weeks. Conducted in USA |
| Participants |
DBP 90 to 105 mmHg. Mean age 37 years. Males 71%. Baseline BP was 135/93 mmHg in the treatment group and 137/93 mmHg in the control group |
| Interventions |
Chlorthalidone 50 mg/d (N = 42) or placebo (N = 42)
Trial duration = 4 weeks |
| Outcomes |
Sitting SBP and DBP; urinalysis (includes urinary sodium, creatinine, catecholamines and norepinephrine), plasma renin activity and serum dopamine β‐hydroxylase enzyme |
| Notes |
A sample size calculation was not provided. The average age of patients included in the study was younger than in most other studies under this review. The study authors stated that there were no statistically significant differences across treatment groups in the baseline patient demographics and characteristics, except for age (average age was 34.5 in chlorthalidone group and 38.9 in placebo group). Baseline BP following randomization was not reported. BP data with SD at 1 month available. Total withdrawals, WDAEs, mortalities, SAEs, total AEs and biochemical data were not reported. Study included a separate group of 116 normotensive patients whose dopamine β‐hydroxylase levels were monitored (not included in the review) |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
"...patients were randomly assigned to receive either active treatment with chlorthalidone 50 mg qam or placebo." (line 32 from top of p.1064). 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 |
"The study was conducted in a double‐blind manner." (line 35 from top of p.1064). No further information was given |
| Incomplete outcome data (attrition bias)
All outcomes |
High risk |
Primary efficacy analysis is not known (was it based on an intention‐to‐treat (ITT) or per‐protocol technique). Exclusions: the number of patients excluded from the "before treatment" period of the study prior to randomization was not given
Attrition: total patient withdrawals and their reasons were not given
WDAEs: not given |
| Selective reporting (reporting bias) |
High risk |
Mean age was the only of the baseline patient demographics and characteristics reported by the study authors. Metabolic data including hematology, serum chemistry, lipids and ECG were not documented (urine sodium and creatinine were included). Mortalities, SAEs and total AEs were not documented |
| Industry sponsorship |
Low risk |
Supported by Research and Development Division, Veterans Administration Hospital and by VA‐NIH Mild Hypertension Cooperative Study #8 |
