Hermida 2007.

Methods	prospective randomized open‐label, blinded endpoint, parallel‐group trial. Subjects ingested the single daily tablet of nifedipine GITS (30 mg/day) for eight weeks. After this first stage of timed treatment, uncontrolled patients were asked to remain in the trial and be up‐titrated to 60 mg/day nifedipine GITS for another eight weeks at the same circadian time. Baseline similarity: age, height, eight, BMI, waist and hip perimeters, BP, laboratory chemistry variables sample size calculation:not reported
Participants	Country: Spain Number randomised: 90, 80 completed Mean age: 52.1±10.7(SD) years gender: 36 men, 44 women. Ethnicity: not reported Inclusion Criteria: conventional SBP between 140 and 179 mm Hg or DBP between 90 and 109 mm Hg, and ABPM 24 hour mean SBP/DBP > 130/80 mm Hg, diurnal mean >135/85 mm Hg, or the nocturnal mean > 120/70 mm Hg. Exclusion criteria: shift workers, heavy drinkers, smokers, heavy exercisers, severe arterial or secondary arterial hypertension, nephropathy and retinopathy and/or cardiovascular disorders
Interventions	nifedipine GITS (30 mg od) on awakening: N=43 nifedipine GITS (30 mg od) at bedtime:N=47 nifedipine GITS (60 mg od) on awakening:N=21 nifedipine GITS (60 mg od) at bedtime:N=19
Outcomes	Mortality: not reported Morbidity: not reported Blood Pressure data: 24h BP change by 48h ABPM, data was obtained from graph and text (fig 6 on page 485) Adverse Events: withdrawals due to adverse events
Notes	supported in part by grants from Ministerio de Educacio´n y Ciencia, Xunta de Galicia , Quımica Farmaceutica Bayer, Hospital Clınico Universitario de Santiago, and University of Vigo
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	computerized random‐number generator
Allocation concealment (selection bias)	High risk	one member of the research team use of a list of random numbers
Blinding (performance bias and detection bias) All outcomes	Low risk	investigator obtaining the BP measurements, outcome assessors blinded. Benefits of the PROBE design and its validity compared with double‐blind, placebo‐controlled trials in assessing antihypertensive efficacy based on blinded ABPM measurements have been documented previously (Smith 2003)
Incomplete outcome data (attrition bias) All outcomes	Low risk	Data on all participants were reported. 90 randomised, 80 completed. At the first stage of timed treatment, 6 lost to follow‐up for no second ABPM available, 1 in daytime group, 5 in bedtime group, 4 withdrawn due to adverse effects, 3 in daytime group, 1 in bedtime group;At the second stage of timed treatment (uncontrolled BP, N=40), 5 discontinued because of adverse effects, 3 in daytime group, 2 in bedtime group
Selective reporting (reporting bias)	High risk	Morning SBP, DBP, overall adverse events, serious adverse events were not reported.
Other bias	Low risk	This trial was a part of MAPEC (http://www.clinicaltrials.gov/ct2/show/NCT00295542?term=NCT00295542). "The funding body has no role in the study design, analysis and interpretation of data, writing of the reports, or the decision to submit articles to publication (Hermida 2007b)".