White 1999a.

Methods	randomized, double blind , double‐dummy, crossover design. 3‐week single blind, placebo run‐in period, 8‐week double‐blind crossover treatment period (each 4 weeks) sample size calculation: yes carryover effects: not reported no washout period between treatment arms
Participants	Country: the United States Number randomised: 85,75 completed Mean age: 57.8±9.1(SD) years gender: 43 men, 32 women, . Ethnicity: 46 White, 26 Black, 2 Hispanic, 1 Asian. Inclusion criteria: age≥21 years, seated office DBP≥90 mm Hg and ≥109 mm Hg exclusion criteria: secondary hypertension, SBP>200 mm Hg or DBP≥110 mm Hg, bradycardia , tachycardia , stroke or myocardial infarction in the previous 6 months, congestive heart failure, clinically significant hepatic or renal disease, uncontrolled diabetes mellitus, life‐style factors such as night‐shift work or regular naps during the daytime, or history of allergy or intolerance to study medications.
Interventions	20 mg nisoldipine ER in the morning , and matching placebo in the evening, N=85 20 mg nisoldipine ER in the evening, and matching placebo in the morning: N=85
Outcomes	Mortality: not reported Morbidity: not reported Blood Pressure data: 24h BP change by 24h ABPM (table 3 on page 809) Adverse Events: not reported
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	randomization schedule
Allocation concealment (selection bias)	Unclear risk	not reported
Blinding (performance bias and detection bias) All outcomes	Low risk	double‐dummy, matching placebo
Incomplete outcome data (attrition bias) All outcomes	Low risk	Data in all patients were reported. eight patient withdrawn for adverse events, two patients were lost to follow‐up.
Selective reporting (reporting bias)	Low risk	All outcomes were reported.
Other bias	Unclear risk	carryover effects were not reported.

BP: blood pressure

SBP: Systolic blood pressure

DBP: diastolic blood pressure

MI: Myocardial infarction

GITS: gastrointestinal therapeutic system

HR: heart rate

ABPM: ambulatory blood pressure monitoring

JNC: Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

ER: extended‐release

SD: standard deviation

SE: standard error

h: hour

BMI: body mass index

WHO: World Health Organization

COER: controlled onset extended release

GRD: graded‐release diltiazem HCl extended‐release

PROBE: prospective, randomized, open‐label, blinded end point

MAPEC: Ambulatory Blood Pressure Monitoring in the Prediction of Cardiovascular Events and Effects of Chronotherapy