Morledge 1986.
| Methods | Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out period = 4 weeks. Multicenter, USA | |
| Participants | SBP ≥ 160 mmHg (patients with isolated systolic hypertension). Mean age 73 years. Males 38.5%. Baseline BP was 176/84 in the treatment group and the control group | |
| Interventions | Chlorthalidone 12.5 mg/d (N = 47), 25 mg/d (N = 43), 50 mg/d (N = 47) or placebo (N = 39) Trial duration = 12 weeks | |
| Outcomes | Sitting and standing SBP and DBP (average of 6 readings at 1, 2, 4, 6, 8, 10 and 12 weeks); BP response rate; pulse rate, ECG, body weight; hematology, urinalysis and serum biochemistry | |
| Notes | A sample size calculation was not provided. Study authors stated that baseline patient demographics and characteristics were comparable across treatment groups (P value > 0.10), except in the case of concomitant illness (P value < 0.05). Number of participants unknown for BP and biochemical data; data on BP from figure only (no standard deviation). Patients received potassium supplements at the discretion of the physician | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "...patients were randomly assigned, according to a computer‐generated code, to one of four treatment groups: chlorthalidone 12.5, 25.0, or 50.0 mg or placebo." (line 5 from top of p.200) |
| Allocation concealment (selection bias) | Unclear risk | Not stated by the study authors |
| Blinding (performance bias and detection bias) All outcomes | Unclear risk | "During the double‐blind treatment period..." (line 17 from top of p.200). Some of the patients received potassium supplements as required which could have broken the blinding. No further information was given |
| Incomplete outcome data (attrition bias) All outcomes | High risk | It is not known if the primary efficacy analysis was based on an intention‐to‐treat (ITT) or per‐protocol population of patients. The study authors did state however, that "patients who failed to respond satisfactorily to their assigned medication could be dropped from the study any time after the first week of treatment, but were included in the statistical analyses of safety and efficacy." (line 12 from top of p.200). The total number of patients presumed to be randomized to treatment was 176 Exclusions: it is not known if any patients were excluded from the study during the wash‐out period prior to randomization Attrition: 36/176 (20%) patients withdrew from the study. 17/176 (10%) of these patients withdrew due to "treatment failures (i.e. unsatisfactory response to treatment)": 6 (13%), 1 (2%), 2 (5%) and 8 (21%) in the chlorthalidone 12.5, 25.0, 50 mg and placebo groups, respectively. It is not known for what reasons the other 19 patients withdrew WDAEs: 19/176 (11%) of patients withdrew due to adverse events (referred to as "adverse reactions"). 3 (6%), 4 (9%), 7 (15%) and 5 (13%) patients from the chlorthalidone 12.5, 25.0, 50.0 mg and placebo groups, respectively. The precise reasons were not given |
| Selective reporting (reporting bias) | High risk | Body weight, pulse rate and ECG were measured but actual values were not shown at endpoint. Results for serum chemistry parameters (except for potassium and uric acid levels), hematology and urinalysis were not shown. Mean BP (from baseline to endpoint) was presented in graph form only (Fig 1 and 2, p.201; no values were shown) and variability was not given Mortalities: 1 patient from the chlorthalidone 50.0 mg group died of "ventricular fibrillation". SAEs: not stated explicitly by the study's authors. The total number of patients with AEs (referred to as "adverse reactions") was shown (chlorthalidone 12.5, 25.0, 50.0 mg and placebo: 22, 23, 31 and 21 patients), but a complete listing of descriptions for the AEs was not; only the 5 most frequently occurring AEs were mentioned in the study (data were pooled) |
| Industry sponsorship | High risk | Supported by a grant from USV Laboratories |