Effectiveness of Night Administration of Low Dose Aspirin in Hypertensive Patients (TAHPS)

Effectiveness of the Timing of the Administration of Aspirin in Hypertensive Patients Treated With Low Doses of Acetyl Salicylic Acid for Secondary Prevention - TAHPS

The goal is to investigate in patients with high blood pressure, BP, namely, those with systolic blood pressure and diastolic blood pressure, SBP/DBP higher than or equal to 140/90 mmHg, and high cardiovascular risk, under treatment with low-dose acetylsalicylic acid, ASA, whether changing the time they take the drug (same dose) to bedtime (from taking it at some point during the active part of the day) produces a drop in their blood pressure (mean systolic and diastolic over 24 hours) of at least 2.5 mm Hg; and also whether among non-dippers, under secondary treatment with low-dose ASA, there is be a greater decrease in their night BP when the drug is taken in the evening.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: ASA evening; Drug: Placebos morning; Drug: Acetylsalicylic morning; Drug: Placebo evening

• Study Type: Interventional
• Enrollment (Actual): 230
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Bizkaia
    • Bilbao, Bizkaia, Spain, 48014
      • Primary care research unit of Bizkaia
  • Catalonia
    • Barcelona, Catalonia, Spain
      • Primary care of IDIAP Jordi Gol
  • Gipuzkoa
    • Gipuzkoa Oeste, Gipuzkoa, Spain
      • Primary care research unit of Bizkaia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Hypertensive patients (≥140/90)
• Patients from 18 to 80 years old
• Patients are currently taking low doses of ASA during the day, for secondary prevention of cardiovascular events
• Patients have been stable for at least one month with their current antihypertensive and antiplatelet therapy.

Exclusion Criteria:

• Severe and/or terminal illness
• Moderate/severe congestive heart failure (CHF), New York Heart Association, NYHA stage ≥ III
• Moderate/severe chronic renal failure glomerular filtration rate <45ml/min.
• Physical or mental illness that prevents the patient´s collaboration
• Being a heavy drinker, consuming more than 280 g of alcohol per week in the case of men or 170 g for women31
• Concomitant treatment with other antiplatelets or anticoagulants
• Taking nonsteroidal antiinflammatory drugs, NSAIDs, on a regular basis
• Treatment with ASA at doses outside those established in the inclusion criteria (above)
• ASA already being taken in the evening
• Being a shift worker or having a very intensive work schedule
• Hospital admission during the clinical trial
• Changes being made in the antihypertensive and antiplatelet therapy taken by the patient during the seven months of the trial
• Patients with unstable treatment or clinical condition requiring frequent adjustments thereof.
• Compliance with less than 90% of the doses, both those for daytime and those for evening administration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASA evening&placebo morning; Patients will receive acetylsalicylic acid (100 mg)in the evening and placebo in the morning.	Drug: ASA evening; Patients will be assigned to one of two parallel groups: Active comparator group during the first two months, namely, administration of acetylsalicylic acid 100 mg, in the morning and placebo in the evening and Experimental: Acetylsalicylic acid in the evening & placebo in the morning group, of administration of acetylsalicylic acid 100 mg in the evening, between (20.00 and 22.00 hours) and placebo in the morning. After that, patients will then undergo a washout period of 15 days to one month, during which all patients participating in the study will take their ASA doses during the daytime. After the washout period, participants will exchange groups; Other Names: ASA; Low dose; aspirine; Drug: Placebos morning; Patients will be assigned to one of two parallel groups: Active comparator group during the first two months, namely, administration of acetylsalicylic acid 100 mg, in the morning and placebo in the evening and Experimental: Acetylsalicylic acid in the evening & placebo in the morning group, of administration of acetylsalicylic acid 100 mg in the evening, between (20.00 and 22.00 hours) and placebo in the morning. After that, patients will then undergo a washout period of 15 days to one month, during which all patients participating in the study will take their ASA doses during the daytime. After the washout period, participants will exchange groups
Active Comparator: ASA morning&placebo evening; Patients will receive acetylsalicylic acid (100 mg) in the morning and placebo in the evening	Drug: Acetylsalicylic morning; Patients will be assigned in a blind and randomized way to one of two parallel groups: group I with the control treatment during the first two months, namely, administration of aspirin 100 mg, in the morning and placebo in the evening and group II initially receiving the intervention, of administration of aspirin 100 mg in the evening, between (20.00 and 22.00 hours) and placebo in the morning. After that, patients will then undergo a washout period of 15 days to one month, during which all patients participating in the study will take their ASA doses during the daytime. After the washout period, participants will exchange groups, i.e., patients randomly allocated to group I, so having taken aspirin in the morning and placebo in the evening, will now receive the intervention treatment, namely, administration of ASA in the evening and placebo in the morning for another two months and vice verse.; Other Names: Low dose; aspirine; Asa; Drug: Placebo evening; Patients will be assigned to one of two parallel groups: Active comparator group during the first two months, namely, administration of acetylsalicylic acid 100 mg, in the morning and placebo in the evening and Experimental: Acetylsalicylic acid in the evening & placebo in the morning group, of administration of acetylsalicylic acid 100 mg in the evening, between (20.00 and 22.00 hours) and placebo in the morning. After that, patients will then undergo a washout period of 15 days to one month, during which all patients participating in the study will take their ASA doses during the daytime. After the washout period, participants will exchange groups

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean SBP and DBP measured with Ambulatory Blood Pressure Monitoring (ABPM) over a 24 hour period	To evaluate the effect of evening administration of low doses of aspirin (100 mg) on the BP of hypertensive patients with high cardiovascular risk, comparing with the effect of day administration, we are going to measure the change in the mean SBP and DBP measured with Ambulatory Blood Pressure Monitoring (ABPM) over a 24 hour period from baseline at the end of the study, five months later.	Change from baseline in sistolyc blood pressure at five months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean of day/night SBP and DBP ratios measured with Ambulatory Blood Pressure monitoring Monitoring	To optimize the control of BP in hypertensive patients treated with low doses of aspirin for secondary prevention. We are going to describe the changes in day-night pattern of BP as a function of the time of administration of low doses of aspirin in non-dipper patients, objectified by the mean of day:night SBP and DBP ratios.	Change from baseline in sistolyc blood pressure at five months
The mean of heart rate (HR) and the mean of pulse pressure (PP)	To optimize the control of BP in hypertensive patients treated with low doses of aspirin for secondary prevention. We are going to identify any changes in the mean of heart rate (HR) and the mean of pulse pressure (PP) with evening administration of ASA.	Change from baseline in sistolyc blood pressure at five months
Percentage of adverse events related to ASA evening administration versus day administration	we are going to measured the percentage of adverse events at the end of the study to assess any changes in the side effects of aspirin when it is taken in the evening compared to day-time administration.	Change from baseline in sistolyc blood pressure at five months

Collaborators and Investigators

• Sponsor: Basque Health Service
• Collaborators: Preventive Services and Health Promotion Research Network; Spanish Clinical Research Network - SCReN; Public Health Service of Cataluña
• Investigators: Principal Investigator: Victoria Ruíz, Dr., Basque Health Service

Publications and helpful links

General Publications

• Ruiz-Arzalluz MV, Fernandez MC, Burgos-Alonso N, Vinyoles E, San Vicente Blanco R, Grandes G; TAHPS group. Protocol for assessing the hypotensive effect of evening administration of acetylsalicylic acid: study protocol for a randomized, cross-over controlled trial. Trials. 2013 Jul 27;14:236. doi: 10.1186/1745-6215-14-236.
• Ruiz Arzalluz MV, Burgos-Alonso N, Garcia-Alvarez A, Gomez Fernandez MC, Vinyoles E, Grandes G; TAHPS Group. Evaluation of the antihypertensive effect of nocturnal administration of acetylsalicylic acid: a cross-over randomized clinical trial. J Hypertens. 2019 Feb;37(2):406-414. doi: 10.1097/HJH.0000000000001887.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2012
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: November 7, 2012
• First Submitted That Met QC Criteria: December 3, 2012
• First Posted (Estimate): December 5, 2012

Study Record Updates

• Last Update Posted (Estimate): February 3, 2017
• Last Update Submitted That Met QC Criteria: February 2, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Hypertension; blood pressure; aspirin; ASA; Low dose
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: TAHPS-2011-004760-29