Chronotherapy with Low-dose Aspirin for Primary Prevention
CARING
2 other identifiers
interventional
3,200
1 country
19
Brief Summary
Brief summary: Aspirin (ASA) has been shown to provide marked benefits in primary and secondary prevention of cardiovascular events. Substantial evidence suggests that low-dose ASA therapy should also be used as a primary prevention strategy in men and women with diabetes who are at high cardiovascular risk. On the other hand, there is current evidence on the potential benefits of low-dose ASA therapy in subjects with impaired fasting glucose, including those with metabolic syndrome. Most important, previous laboratory animal and clinical trial research convincingly demonstrates administration time-dependent (with reference to circadian rhythms) effects of ASA. Thus, the effects of ASA upon lipoperoxides, b-adrenergic receptors, and blood pressure (BP) in clinically healthy subjects depend on the circadian timing of ASA administration. The administration-time-dependent influence of ASA on BP was previously demonstrated in a randomized trial on healthy women and other independent double-blind, randomized, placebo-controlled clinical trials conducted, first, on clinically healthy subjects, a second one on normotensive and hypertensive subjects, a third one on pregnant women at high risk for preeclampsia and a fourth one in previously untreated patients with mild hypertension. The findings of these BP studies are consistent; BP-lowering effect of low-dose ASA is achieved when administered at bedtime but not upon awakening. In keeping with the chronopharmacological effects of ASA and the previous findings suggesting that ASA at low dose may exert a potential beneficial effect on BP, endothelium function and cardiovascular function, this prospective, randomized, parallel-arm study will investigate the potential influence of ASA on the primary prevention of cardiovascular, cerebrovascular and renal events in subjects with either impaired fasting glucose (≥ 100 mg/dl) or previous diagnosis of type 2 diabetes mellitus, who will receive low-dose ASA (100 mg/day) at different circadian times (upon awakening or at bedtime) in relation to their rest-activity cycle.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4 type-2-diabetes
Started Oct 2008
Longer than P75 for phase_4 type-2-diabetes
19 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 28, 2008
CompletedFirst Posted
Study publicly available on registry
July 30, 2008
CompletedStudy Start
First participant enrolled
October 1, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
June 30, 2026
ExpectedDecember 6, 2024
December 1, 2024
17.3 years
July 28, 2008
December 3, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To evaluate the effects of awakening vs. bedtime 100 mg/day ASA administration in subjects with impaired fasting glucose or type 2 diabetes on primary prevention of cardiovascular, cerebrovascular and renal fatal, and non-fatal events.
Five years
Secondary Outcomes (8)
To evaluate the effects of awakening vs. bedtime 100 mg/day ASA administration on primary prevention of cardiovascular fatal and non-fatal events (including cardiovascular death, myocardial infarction, angina pectoris, and coronary revascularization).
Five years
To evaluate the effects of awakening vs. bedtime 100 mg/day ASA administration on primary prevention of cerebrovascular fatal and non-fatal events (including hemorrhagic stroke, ischemic stroke, and transient ischemic attack).
Five years
To evaluate the effects of awakening vs. bedtime 100 mg/day ASA administration on primary prevention of chronic kidney disease and/or congestive heart failure, and/or peripheral artery disease.
Five years
To demonstrate that 100 mg/day ASA at bedtime offers a similar safety profile than 100 mg/day ASA upon awakening
Five years
To demonstrate that compliance with 100 mg/day ASA at bedtime is similar to that with 100 mg/day ASA upon awakening.
Five years
- +3 more secondary outcomes
Study Arms (2)
1
ACTIVE COMPARATOR100 mg/day ASA upon awakening.
2
ACTIVE COMPARATOR100 mg/day ASA at bedtime
Interventions
Eligibility Criteria
You may qualify if:
- Male or female subjects ≥ 50 years of age.
- Impaired fasting glucose (≥ 100 and \< 126 mg/dl) in the last available blood test prior (≤ 3 months) to randomization, or diagnosis of type 2 diabetes prior to randomization.
- All subjects must have at randomization a conventional clinic systolic/diastolic BP \< 160/100 mmHg.
- Informed consent to participate in the study prior to any study procedures.
You may not qualify if:
- Known or suspected contraindications, including history of allergy to ASA.
- Uncontrolled essential hypertension of Grade 2-3, i.e., systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 100 mmHg before randomization.
- Evidence of a secondary form of hypertension, to include coarctation of the aorta, hyperaldosteronism, renal artery stenosis, or pheochromocytoma.
- Known Keith-Wagener grade III or IV hypertensive retinopathy.
- History of hypertensive encephalopathy, cerebrovascular event, transient ischemic cerebral attack, or myocardial infarction prior to randomization.
- Type 1 diabetes mellitus.
- History of heart failure.
- Second or third degree heart block without a pacemaker.
- Concomitant unstable angina pectoris.
- Concomitant potentially life threatening arrhythmia or symptomatic arrhythmia.
- Clinically significant valvular heart disease.
- Evidence of hepatic disease as determined by one of the following: ALT or AST values \> 2 x UNL known before randomization, a history of hepatic encephalopathy, history of esophageal varices, or history of portocaval shunt.
- Diagnosis of chronic kidney disease prior to randomization.
- History of malignancy including leukemia and lymphoma (but not basal cell skin cancer), or any other severe, life-threatening disease within the past five years.
- Any previous history of a systemic autoimmune disease.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (19)
CS Friol
Friol, Lugo, 27220, Spain
CS Fingoi
Lugo, Lugo, 27002, Spain
Complexo Hospitalario Universitario de Ourense
Ourense, Orense, 32005, Spain
CS A Estrada
A Estrada, Pontevedra, 26680, Spain
CS Baiona
Baiona, Pontevedra, 36300, Spain
CS Bueu
Bueu, Pontevedra, 36930, Spain
CS A Guarda
La Guardia, Pontevedra, 36780, Spain
CS Valmiñor
Nigrán, Pontevedra, 36250, Spain
CS Panxón
Nigrán, Pontevedra, 36340, Spain
CS Lerez
Pontevedra, Pontevedra, 36156, Spain
CS Tomiño
Tomiño, Pontevedra, 36200, Spain
Bioengineering & Chronobilogy Labs., University of Vigo
Vigo, Pontevedra, 36200, Spain
CS Calle Cuba
Vigo, Pontevedra, 36202, Spain
CS A Doblada
Vigo, Pontevedra, 36205, Spain
CS Coia
Vigo, Pontevedra, 36209, Spain
CS Sardoma
Vigo, Pontevedra, 36214, Spain
CS Teis
Vigo, Pontevedra, 36216, Spain
CS Vilaboa
Vilaboa, Pontevedra, 36141, Spain
CS San Roque
Vilagarcía de Arousa, Pontevedra, 36600, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Ramon C Hermida, PhD
University of Vigo
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
July 28, 2008
First Posted
July 30, 2008
Study Start
October 1, 2008
Primary Completion
December 31, 2025
Study Completion (Estimated)
June 30, 2026
Last Updated
December 6, 2024
Record last verified: 2024-12