Chronotherapy With Low-dose Aspirin for Primary Prevention (CARING)

May 8, 2023 updated by: Ramon C. Hermida, University of Vigo

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

3200

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Spain
      • Lugo, Spain, 27002
        • Recruiting
        • CS Fingoi
        • Contact:
        • Principal Investigator:
          • Carmen Castiñeira, MD
        • Sub-Investigator:
          • Maria C Aguado
        • Sub-Investigator:
          • Carmen Costa
        • Sub-Investigator:
          • Domingo D Garcia, MD
        • Sub-Investigator:
          • Bernardino Pardo, MD
        • Sub-Investigator:
          • Enrique J Vazquez, MD
      • Orense, Spain, 32005
        • Recruiting
        • Complexo Hospitalario Universitario de Ourense
        • Contact:
        • Principal Investigator:
          • Alfonso Otero, MD, PhD
      • Pontevedra, Spain, 36156
        • Recruiting
        • CS Lerez
        • Contact:
        • Principal Investigator:
          • Ana Moya, MD
        • Sub-Investigator:
          • Andres Ruiz, MD
        • Sub-Investigator:
          • Aurelia Constenla
        • Sub-Investigator:
          • Maria I Franco
    • Lugo
      • Friol, Lugo, Spain, 27220
        • Recruiting
        • CS Friol
        • Contact:
        • Principal Investigator:
          • Esther Gomez, MD
    • Pontevedra
      • Baiona, Pontevedra, Spain, 36300
      • Bueu, Pontevedra, Spain, 36930
      • La Estrada, Pontevedra, Spain, 26680
        • Recruiting
        • CS A Estrada
        • Contact:
        • Principal Investigator:
          • Luis Meijide, MD
        • Sub-Investigator:
          • Mariana Carbon, MD
        • Sub-Investigator:
          • Maria C Garcia, MD
        • Sub-Investigator:
          • Francisco Romero, MD
        • Sub-Investigator:
          • Maria P Brea
      • La Guardia, Pontevedra, Spain, 36780
        • Recruiting
        • CS A Guarda
        • Contact:
        • Principal Investigator:
          • Juan J Crespo, MD
        • Sub-Investigator:
          • Raquel Fernandez, MD
        • Sub-Investigator:
          • Carmen M Fernandez, MD
        • Sub-Investigator:
          • Amelia Ferreras, MD
        • Sub-Investigator:
          • Manuel F Quintans, MD
        • Sub-Investigator:
          • Javier Rodriguez, MD
        • Sub-Investigator:
          • Pilar Rua
        • Sub-Investigator:
          • Aurelio Alvarez
        • Sub-Investigator:
          • Asuncion Cadilla
        • Sub-Investigator:
          • Carmen Outeiro
        • Sub-Investigator:
          • Carmen Soto-Davila
      • Nigran, Pontevedra, Spain, 36250
        • Recruiting
        • CS Valmiñor
        • Contact:
        • Principal Investigator:
          • Susana Hernaiz, MD
      • Nigrán, Pontevedra, Spain, 36340
        • Recruiting
        • CS Panxón
        • Contact:
        • Principal Investigator:
          • Jose L Salgado, MD
        • Sub-Investigator:
          • Esperanza Parrado
        • Sub-Investigator:
          • Alfredo Pereira
      • Tomiño, Pontevedra, Spain, 36200
        • Recruiting
        • CS Tomiño
        • Contact:
        • Principal Investigator:
          • Evangelina Filloy, MD
        • Sub-Investigator:
          • Adolfo T Perez, MD
        • Sub-Investigator:
          • Nieves Turienzo, MD
        • Sub-Investigator:
          • Dolores Cardalda
        • Sub-Investigator:
          • Jose C Varela
        • Sub-Investigator:
          • Francisca Vazquez
      • Vigo, Pontevedra, Spain, 36200
        • Recruiting
        • Bioengineering & Chronobilogy Labs., University of Vigo
        • Contact:
        • Contact:
        • Principal Investigator:
          • Ramon C Hermida, PhD
        • Principal Investigator:
          • Diana E Ayala, MD, PhD
        • Sub-Investigator:
          • Artemio Mojon, PhD
        • Sub-Investigator:
          • Jose R Fernandez, PhD
        • Sub-Investigator:
          • Ignacio Alonso, PhD
        • Sub-Investigator:
          • Maria J Fontao
        • Sub-Investigator:
          • Rita Soler
        • Sub-Investigator:
          • Susana Serrano
      • Vigo, Pontevedra, Spain, 36202
        • Recruiting
        • CS Calle Cuba
        • Contact:
        • Principal Investigator:
          • Felisa Dominguez, MD
      • Vigo, Pontevedra, Spain, 36205
        • Recruiting
        • CS A Doblada
        • Contact:
        • Principal Investigator:
          • Teresa Rios, MD
      • Vigo, Pontevedra, Spain, 36209
        • Recruiting
        • CS Coia
        • Contact:
        • Principal Investigator:
          • Peregrina Eiroa, MD
        • Sub-Investigator:
          • Jesus C Nieto, MD
      • Vigo, Pontevedra, Spain, 36214
        • Recruiting
        • CS Sardoma
        • Contact:
        • Principal Investigator:
          • Manuel Domínguez, MD, PhD
      • Vigo, Pontevedra, Spain, 36216
      • Vilaboa, Pontevedra, Spain, 36141
        • Recruiting
        • CS Vilaboa
        • Contact:
        • Principal Investigator:
          • Sonia M Gomara, MD
        • Sub-Investigator:
          • Julio J Alvarez, MD
        • Sub-Investigator:
          • Margarita Estevez
        • Sub-Investigator:
          • Maria C Ferreira
      • Vilagarcía De Arousa, Pontevedra, Spain, 36600
        • Recruiting
        • CS San Roque
        • Contact:
        • Principal Investigator:
          • Elvira Sineiro, MD
        • Sub-Investigator:
          • Margarita Alvariño
        • Sub-Investigator:
          • Luis M Fontenla
        • Sub-Investigator:
          • Margarita Fraga, MD
        • Sub-Investigator:
          • Barbara Llovo
        • Sub-Investigator:
          • Rita Martinez
        • Sub-Investigator:
          • Santiago Santidrian, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1
100 mg/day ASA upon awakening.
Drug: aspirin
100 mg/day upon awakening for five years
Other Names:
  • Aspirin on awakening
Drug: aspirin
100 mg/day at bedtime for five years
Other Names:
  • Aspirin at bedtime
Active Comparator: 2
100 mg/day ASA at bedtime
Drug: aspirin
100 mg/day upon awakening for five years
Other Names:
  • Aspirin on awakening
Drug: aspirin
100 mg/day at bedtime for five years
Other Names:
  • Aspirin at bedtime

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Five years

Secondary Outcome Measures

Outcome Measure
Time Frame
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
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).
Time Frame: Five years
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.
Time Frame: Five years
Five years
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
Five years
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
Five years
To evaluate, for all previous objectives, potential gender differences in the benefits of low-dose ASA for primary prevention.
Time Frame: Five years
Five years
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
Five years
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
Five years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Vigo

Investigators

  • Study Director: Ramon C Hermida, PhD, University of Vigo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2008

Primary Completion (Anticipated)

December 1, 2025

Study Completion (Anticipated)

June 1, 2026

Study Registration Dates

First Submitted

July 28, 2008

First Submitted That Met QC Criteria

July 28, 2008

First Posted (Estimate)

July 30, 2008

Study Record Updates

Last Update Posted (Actual)

May 9, 2023

Last Update Submitted That Met QC Criteria

May 8, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CARING-2008/1
  • 2008-002669-30

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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