Chronotherapy With Low-dose Aspirin for Primary Prevention (CARING)
This study is currently recruiting participants.
Verified December 2012 by University of Vigo
Sponsor:
University of Vigo
Information provided by (Responsible Party):
Ramon C. Hermida, University of Vigo
ClinicalTrials.gov Identifier:
NCT00725127
First received: July 28, 2008
Last updated: December 20, 2012
Last verified: December 2012
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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: | December 20, 2012 |
| 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 June 18, 2013