De Plean 1981.

Methods	Randomized, double‐blind, cross‐over study. Each treatment period lasted for 4 weeks. BP was measured about 6 hours after drug intake. Mean of 2 or 3 readings is used for BP data
Participants	16 participants entered the study. 10/16 participants completed the study. 1 person WDAE Age range: 30‐56 years Baseline: mean SBP 163.9 mmHg, mean DBP 117.1 mmHg, mean HR 88.8 beats per minute, mean body weight 83.2 kg
Interventions	Penbutolol 80 mg once daily, hydrochlorothiazide 100 mg once daily, placebo
Outcomes	Supine and standing SBP, DBP, HR Biochemical data Total withdrawal and WDAE
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"The order of the active treatments was selected according to a predetermined random code"
Allocation concealment (selection bias)	Unclear risk	No information
Blinding (performance bias and detection bias) All outcomes	High risk	"Both active drugs and placebo were available in capsules of identical size, shape and color", but pulse would unblind BP measurements
Incomplete outcome data (attrition bias) Primary and secondary outcomes	Low risk	Reported SBP, DBP and HR
Selective reporting (reporting bias)	Low risk	SBP and DBP were primary outcomes HR and WDAE were reported