Chronotherapy With Low-Dose Aspirin for Primary Prevention - Full Text View

Sponsor:	University of Vigo
Information provided by:	University of Vigo
ClinicalTrials.gov Identifier:	NCT00725127

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
Impaired Fasting Glucose Type 2 Diabetes	Drug: aspirin	Phase IV

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
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:

MedlinePlus related topics: Angina Diabetes Heart Attack

Drug Information available for: Acetylsalicylic acid

U.S. FDA Resources

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 2017
Estimated Primary Completion Date:	December 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator 100 mg/day ASA upon awakening.	Drug: aspirin 100 mg/day upon awakening for five years
2: Active Comparator 100 mg/day ASA at bedtime	Drug: aspirin 100 mg/day at bedtime for five years

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 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
Spain, Lugo
CS Friol	Recruiting
Friol, Lugo, Spain, 27220
Contact: Esther Gomez, MD 34639512093 Esther.Gomez.Sal@sergas.es
Principal Investigator: Esther Gomez, MD
Spain, Pontevedra
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 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 Sardoma	Recruiting
Vigo, Pontevedra, Spain, 36214
Contact: Manuel Dominguez, MD, PhD 34986416324 Manuel.Dominguez.Sardina@sergas.es
Principal Investigator: Manuel Dominguez, MD, PhD
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
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 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
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 Teis	Recruiting
Vigo, Pontevedra, Spain, 36216
Contact: Pedro A Callejas, MD 34986374229 PedroAntonio.Callejas.Cabanillas@sergas.es
Principal Investigator: Pedro A Callejas, 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 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 Valmiñor	Recruiting
Nigran, Pontevedra, Spain, 36250
Contact: Susana Hernaiz, MD 34655391498 Susana.Hernaiz.Valero@sergas.es
Principal Investigator: Susana Hernaiz, 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 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 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
Hospital do Meixoeiro	Recruiting
Vigo, Pontevedra, Spain, 36200
Contact: Roberto Perez, MD 34627517077 roberto.perez.alvarez@sergas.es
Principal Investigator: Roberto Perez, MD

Sponsors and Collaborators

University of Vigo

Investigators

Study Director:

Ramon C Hermida, PhD

University of Vigo

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	University of Vigo ( Ramon C. Hermida )
Study ID Numbers:	CARING-2008/1, 2008-002669-30
Study First Received:	July 28, 2008
Last Updated:	April 28, 2009
ClinicalTrials.gov Identifier:	NCT00725127 History of Changes
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:

Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Hematologic Agents
Prediabetic State
Fibrinolytic Agents
Fibrin Modulating Agents
Aspirin
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Metabolic Diseases

Cyclooxygenase Inhibitors
Diabetes Mellitus
Endocrine System Diseases
Enzyme Inhibitors
Cardiovascular Agents
Pharmacologic Actions
Analgesics, Non-Narcotic
Diabetes Mellitus, Type 2
Platelet Aggregation Inhibitors
Peripheral Nervous System Agents
Glucose Metabolism Disorders
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on November 20, 2009