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NCT Number: NCT00725127

Chronotherapy with Low-dose Aspirin for Primary Prevention

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.

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Key information

Conditions

Type 2 Diabetes Angina Pectoris Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Chest Pain Chronic Disease Diabetes Mellitus Diabetes Mellitus, Type 2 Disease Attributes Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Glucose Metabolism Disorders Heart Diseases Infarction Ischemia Kidney Diseases Male Urogenital Diseases Metabolic Diseases Myocardial Infarction Myocardial Ischemia Necrosis Nervous System Diseases Neurologic Manifestations Nutritional and Metabolic Diseases Pain Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Renal Insufficiency, Chronic Signs and Symptoms Stroke Urogenital Diseases Urologic Diseases Vascular Diseases

Age range

50 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

CS Friol, Friol, Lugo, Spain

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.
  • History of drug or alcohol abuse within the last two years.
  • Use of any disallowed concomitant medication.
  • Inability to communicate and comply with all study requirements.
  • Persons directly involved in the execution of this protocol.

Treatment and study plan

Aspirin

Drug

100 mg/day upon awakening for five years

Other names: Aspirin on awakening

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.

    Time frame: Five years

Secondary outcomes

  1. 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).

    Time frame: Five years

  2. 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).

    Time frame: Five years

  3. 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.

    Time frame: Five years

  4. To demonstrate that 100 mg/day ASA at bedtime offers a similar safety profile than 100 mg/day ASA upon awakening

    Time frame: Five years

  5. To demonstrate that compliance with 100 mg/day ASA at bedtime is similar to that with 100 mg/day ASA upon awakening.

    Time frame: Five years

  6. To evaluate, for all previous objectives, potential gender differences in the benefits of low-dose ASA for primary prevention.

    Time frame: Five years

  7. To evaluate, for all previous objectives, potential differences in the benefits of low-dose ASA for primary prevention between patients with and without diabetes.

    Time frame: Five years

  8. To evaluate, for all previous objectives, potential differences in the benefits of low-dose ASA for primary prevention between subjects with and without metabolic syndrome.

    Time frame: Five years

Sponsors and collaborators

Lead sponsor

University of Vigo

Other

Registry information

Official study title

Chronotherapy with Low-dose Aspirin for Primary Prevention of Cardiovascular Events in Subjects with Impaired Fasting Glucose or Diabetes (CARING Study).

Acronym: CARING

Important dates

Study start
2008
Primary completion
2025
Study completion
2026
First posted
Jul 30, 2008
Registry last updated
Dec 6, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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