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

This study is currently recruiting participants.
Verified March 2014 by University of Vigo
Sponsor:
Information provided by (Responsible Party):
Ramon C. Hermida, University of Vigo
ClinicalTrials.gov Identifier:
NCT00725127
First received: July 28, 2008
Last updated: March 18, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes
Drug: aspirin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Chronotherapy With Low-dose Aspirin for Primary Prevention of Cardiovascular Events in Subjects With Impaired Fasting Glucose or Diabetes (CARING Study).

Resource links provided by NLM:


Further study details as provided by University of Vigo:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • To evaluate, for all previous objectives, potential gender differences in the benefits of low-dose ASA for primary prevention. [ Time Frame: Five years ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 3200
Study Start Date: October 2008
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
100 mg/day ASA upon awakening.
Drug: aspirin
100 mg/day upon awakening for five years
Other Name: Aspirin on awakening
Active Comparator: 2
100 mg/day ASA at bedtime
Drug: aspirin
100 mg/day at bedtime for five years
Other Name: Aspirin at bedtime

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00725127

Contacts
Contact: Ramon C Hermida, PhD 34986812148 rhermida@uvigo.es
Contact: Diana E Ayala, MD, PhD 34986812148 dianaelva@hotmail.com

Locations
Spain
CS Friol Recruiting
Friol, Lugo, Spain, 27220
Contact: Esther Gomez, MD    34639512093    Esther.Gomez.Sal@sergas.es   
Principal Investigator: Esther Gomez, MD         
CS Bayona Recruiting
Bayona, Pontevedra, Spain, 36300
Contact: Francisco J Iglesias, MD    34986357239    FranciscoJavier.Iglesias.Mato@sergas.es   
Principal Investigator: Francisco J Iglesias, MD         
CS Bueu Recruiting
Bueu, Pontevedra, Spain, 36930
Contact: Miguel A Aboal, MD    34986323313    miguel.angel.aboal.beato@sergas.es   
Principal Investigator: Miguel A Aboal, MD         
CS A Estrada Recruiting
La Estrada, Pontevedra, Spain, 26680
Contact: Luis Meijide, MD    34986573459    Luis.Meijide.Calvo@sergas.es   
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         
CS A Guarda Recruiting
La Guardia, Pontevedra, Spain, 36780
Contact: Juan J Crespo, MD    34986614450    JuanJose.Crespo.Sabaris@sergas.es   
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         
CS Valmiñor Recruiting
Nigran, Pontevedra, Spain, 36250
Contact: Susana Hernaiz, MD    34655391498    Susana.Hernaiz.Valero@sergas.es   
Principal Investigator: Susana Hernaiz, MD         
CS Panxón Recruiting
Nigrán, Pontevedra, Spain, 36340
Contact: Jose L Salgado, MD    34986368615    joseluis.salgado.conde@sergas.es   
Principal Investigator: Jose L Salgado, MD         
Sub-Investigator: Esperanza Parrado         
Sub-Investigator: Alfredo Pereira         
CS Tomiño Recruiting
Tomiño, Pontevedra, Spain, 36200
Contact: Evangelina Filloy, MD    34-986-623411    evangelina.filloy.miguez@sergas.es   
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         
Bioengineering & Chronobilogy Labs., University of Vigo Recruiting
Vigo, Pontevedra, Spain, 36200
Contact: Ramon C Hermida, PhD    34986812148    rhermida@uvigo.es   
Contact: Diana E Ayala, MD, PhD    34986812148    dianaelva@uvigo.es   
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         
CS Sardoma Recruiting
Vigo, Pontevedra, Spain, 36214
Contact: Manuel Dominguez, MD, PhD    34986416324    Manuel.Dominguez.Sardina@sergas.es   
Principal Investigator: Manuel Dominguez, MD, PhD         
CS Teis Recruiting
Vigo, Pontevedra, Spain, 36216
Contact: Pedro A Callejas, MD    34986374229    PedroAntonio.Callejas.Cabanillas@sergas.es   
Principal Investigator: Pedro A Callejas, MD         
CS A Doblada Recruiting
Vigo, Pontevedra, Spain, 36205
Contact: Teresa Rios, MD    34986275121    teresa.rios.rey@sergas.es   
Principal Investigator: Teresa Rios, MD         
CS Calle Cuba Recruiting
Vigo, Pontevedra, Spain, 36202
Contact: Felisa Dominguez, MD    34986416226    fdominguez@meditex.es   
Principal Investigator: Felisa Dominguez, MD         
Hospital do Meixoeiro Recruiting
Vigo, Pontevedra, Spain, 36200
Contact: Roberto Perez, MD    34627517077    roberto.perez.alvarez@sergas.es   
Principal Investigator: Roberto Perez, MD         
CS Coia Recruiting
Vigo, Pontevedra, Spain, 36209
Contact: Peregrina Eiroa, MD    34986209282    pereeiroa@telefonica.net   
Principal Investigator: Peregrina Eiroa, MD         
Sub-Investigator: Jesus C Nieto, MD         
CS Vilaboa Recruiting
Vilaboa, Pontevedra, Spain, 36141
Contact: Sonia M Gomara, MD    34986679229    SoniaMaria.Gomara.Villabona@sergas.es   
Principal Investigator: Sonia M Gomara, MD         
Sub-Investigator: Julio J Alvarez, MD         
Sub-Investigator: Margarita Estevez         
Sub-Investigator: Maria C Ferreira         
CS San Roque Recruiting
Villagarcia de Arosa, Pontevedra, Spain, 36600
Contact: Envira Sineiro, MD    34986507448    Elvira.Sineiro.Galinanes@sergas.es   
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         
CS Fingoi Recruiting
Lugo, Spain, 27002
Contact: Carmen Castiñeira, MD    34982251035    Carmen.Castineira.Perez@sergas.es   
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         
Complexo Hospitalario Universitario de Ourense Recruiting
Orense, Spain, 32005
Contact: Alfonso Otero, MD, PhD    34988385625    Alfonso.Santiago.Otero.Gonzalez@sergas.es   
Principal Investigator: Alfonso Otero, MD, PhD         
CS Lerez Recruiting
Pontevedra, Spain, 36156
Contact: Ana Moya, MD    34986871496    ana.moya.alvarez@sergas.es   
Principal Investigator: Ana Moya, MD         
Sub-Investigator: Andres Ruiz, MD         
Sub-Investigator: Aurelia Constenla         
Sub-Investigator: Maria I Franco         
Sponsors and Collaborators
University of Vigo
Investigators
Study Director: Ramon C Hermida, PhD University of Vigo
  More Information

Additional Information:
No publications provided

Responsible Party: Ramon C. Hermida, Professor, University of Vigo
ClinicalTrials.gov Identifier: NCT00725127     History of Changes
Other Study ID Numbers: CARING-2008/1, 2008-002669-30
Study First Received: July 28, 2008
Last Updated: March 18, 2014
Health Authority: Spain: Ministry of Health

Keywords provided by University of Vigo:
Aspirin
Chronotherapy
Primary prevention
Impaired fasting glucose
Type 2 diabetes
Total mortality
Myocardial infarction
Stroke
Angina pectoris
Chronic kidney disease

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Aspirin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents

ClinicalTrials.gov processed this record on April 14, 2014