title: Protocol for assessing the hypotensive effect of evening administration of acetylsalicylic acid: study protocol for a randomized, cross-over controlled trial.
abstract: BACKGROUND
  The objective of this study is to evaluate the antihypertensive effect of bedtime administration of low doses of aspirin in patients with treated hypertension and high cardiovascular risk on low-dose aspirin for secondary prevention, in order to optimize their usual treatment and reduce their cardiovascular risk.
  
  
  METHODS
  This is a prospective phase IV multicentre, randomised, triple-blind, placebo-controlled, cross-over clinical trial. We will include 258 individuals with hypertension treated with low-dose aspirin for secondary prevention. These patients will be randomly recruited, by approximately 40 primary care physicians collaborating in the study, mainly in the Guipúzcoa West, Bilbao and Barcelona areas. The 258 patients will be randomly allocated to treatments to create two comparable groups. In the first period, the intervention group will take aspirin at night and placebo in the morning, while the control group will take their aspirin in the morning and placebo in the evening for 2 months. After a washout period of 15 to 30 days, there will be a second 2-month period for which groups will swap treatments. Participants will undergo ambulatory blood pressure monitoring at baseline, at the end of first period and then again at the beginning and end of the second period. The main outcome measure is the change in mean blood pressure over 24 h, and as secondary outcomes we will also assess changes in systolic and diastolic blood pressure, during the day and night, and the relationship between them. Lastly, we will explore whether non-dipper patients convert into dippers with the intervention.
  
  
  CONCLUSIONS
  The goal of this research is to provide the scientific basis for indicating a change in the time of aspirin administration from morning to evening, by primary health practitioners, to improve the patient control of blood pressure and more effectively reduce their cardiovascular risk, by combining this hypotensive effect with the well-known anti-platelet effect of low-dose aspirin.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01741922.
authors.affiliation: Primary Care Research Unit-Bizkaia, Basque Health Service (Osakidetza), Bilbao, Spain. MARIAVICTORIALOURDES.RUIZARZALLUZ@osakidetza.net
authors.forename: Ma Victoria
authors.initials: MV
authors.lastname: Ruíz-Arzalluz
authors.forename: Ma Cruz Gómez
authors.initials: MC
authors.lastname: Fernández
authors.forename: Natalia
authors.initials: N
authors.lastname: Burgos-Alonso
authors.forename: Ernest
authors.initials: E
authors.lastname: Vinyoles
authors.forename: Ricardo
authors.initials: R
authors.lastname: San Vicente Blanco
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Grandes
mesh_terms: D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001241:Aspirin / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D002940:Circadian Rhythm; D002985:Clinical Protocols; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011446:Prospective Studies; D012107:Research Design; D055502:Secondary Prevention / Q000379:methods*; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D010975:Platelet Aggregation Inhibitors; D001241:Aspirin
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