Yodfat 1993.

Methods	Multi‐centre study Randomization: "...all patients were randomly assigned to receive one of the three treatments...." Blinding: "...double blind active treatment....placebo...." Withdrawals: "Twenty‐one patients withdrew from the study, the majority during the titration period. Seventy patients discontinued the double‐blind treatment, of whom 60 were followed until the end of the study."; Reasons for discontinuation of therapy (e.g.. critical cardiac events, lack of efficacy, adverse reaction) in each treatment arm was described in the study for the 70 patients in the double‐blind treatment. No details provided regarding the 21 patients who withdrew from the study in terms of which treatment arm they withdrew from and reasons for withdrawing from the study. Lost to follow‐up: not reported (actual number of patients included in each treatment arm when describing results of study was not reported) Treatment duration: active treatment period and follow‐up for one year; patients visited clinic every two weeks during placebo run‐in and dose titration periods, then monthly until end of study period Analysis type: reported as "intention to treat" but unable to assess and confirm (actual number of patients included in each treatment arm when describing results of study was not reported)
Participants	Geographic region: Israel Study setting: not reported N=368 Age range: 40‐65 Gender: males only Race: not reported Blood pressure at entry: Methyldopa arm (152.0/99.3); Placebo arm (150.7/99.8); Isradipine arm (154.5/99.7) Co‐morbid conditions: none of the patients had a history of alcohol abuse, mental disorder, or insulin‐dependent diabetes mellitus Inclusion criteria: essential hypertension; sitting diastolic blood pressure 95‐105 mm Hg Exclusion criteria: secondary hypertension; malignant hypertension; unstable angina; recent myocardial infarction; any clinically relevant cardiovascular disease; any abnormal laboratory findings (including liver function tests and creatinine levels up to 1.5 mg/100 mL)
Interventions	Patients had two to four week single‐blinded placebo washout period before entering trial Methyldopa arm (N=120) 250 mg twice daily x 4 weeks increase to 500 mg twice daily x 2 weeks (if necessary to maintain diastolic blood pressure below 95 mm Hg) add captopril 25 mg daily x 2 weeks (if necessary to maintain diastolic blood pressure below 95 mm Hg) increase captopril to 50 mg daily x 2 weeks (if necessary to maintain diastolic blood pressure below 95 mm Hg) Placebo arm (N=124) twice daily x 4 weeks twice daily x 2 weeks add captopril 25 mg daily x 2 weeks (if necessary to maintain diastolic blood pressure below 95 mm Hg) increase captopril to 50 mg daily x 2 weeks (if necessary to maintain diastolic blood pressure below 95 mm Hg) Isradipine arm (N=124) 1.25 mg twice daily x 4 weeks increase to 2.5 mg twice daily x 2 weeks (if necessary to maintain diastolic blood pressure below 95 mm Hg) add captopril 25 mg daily x 2 weeks (if necessary to maintain diastolic blood pressure below 95 mm Hg) increase captopril to 50 mg daily x 2 weeks (if necessary to maintain diastolic blood pressure below 95 mm Hg) Patients entered final one month single‐blind placebo period at end of trial
Outcomes	Sitting blood pressure Sitting heart rate Clinical symptoms Side effects (most frequently reported: shortness of breath, chest pain palpitations, sleep disorders, sexual disorders, headache, fatigue, heartburn, nausea, vomiting, diarrhoea, constipation, abdominal pain)
Notes	No useable data obtained from this study as the actual number of patients in each treatment arm when describing outcomes was not reported. Assessment of medication compliance: not reported Final number of patients included in each arm when reporting results: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Unclear risk	"...all patients were randomly assigned to receive one of the three treatments...."
Allocation concealment?	Unclear risk	Not reported
Blinding? All outcomes	Low risk	Double blind
Incomplete outcome data addressed? All outcomes	High risk	Actual number of patients in each treatment arm when describing outcomes was not reported No details provided regarding the 20 patients who withdrew from the study in terms of reasons or from which treatment arm they withdrew No details provided for the 10 patients who discontinued therapy with a reason but were not followed until the end of the study
Free of selective reporting?	Low risk	Reported on all pre‐specified outcomes of interest