Hipótesis: el tratamiento con alopurinol (600 mg/día) en pacientes diabéticos resistentes a aspirina con enfermedad coronaria establecida podría favorecer el efecto antiplaquetario de la aspirina e inducir cambios en el perfil de expresión proteico de estas células Hypothesis: treatment with allopurinol (600 mg/day) in diabetic patients resistant to aspirin with established coronary disease could enhance the antiplatelet effect of aspirin and induce changes in its protein expression profile
Conditions
Interventions
Pharmaceutical Form: Tablet
INN or Proposed INN: ALOPURINOL
CAS Number: 315-30-0
Other descriptive name: ALLOPURINOL
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number:
Sponsors
Fundación Investigación Biomedica. Hospital Clinico San Carlos
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Pacientes con diabetes tipo II. -Pacientes con valores de PFA-100 ? 193 segundos. -HbA1c ?10 % obtenida en el momento de la selección o durante las 4 semanas previas. -AST/ALT 30 ml/min (MDRD) -Historia de enfermedad arterial coronaria documentada definida como estenosis > 50% en ? 1 arteria coronaria principal, clínicamente estable durante al menos 1 año. -Pacientes que reciban hasta 162 mg/día de AAS como tratamiento antiplaquetario durante al menos 12 meses y haber tomado la última dosis al menos 24 horas antes de su inclusión en el estudio. -Firma del consentimiento informado -Patients with type II diabetes. -Patients with values of PFA-100 ? 193 seconds. -HbA1c ? 10% obtained at the time of selection or during the previous 4 weeks. -AST/ALT 30 ml / min (MDRD) -History of documented coronary artery disease defined as> 50% stenosis in ? 1 major coronary artery, clinically stable for at least 1 year. -Patients who received up to 162 mg / day of aspirin as antiplatelet therapy for at least 12 months after the last dose at least 24 hours before inclusion in the study. -Signed informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: -Pacientes con valores de PFA-100 > 193 segundos. -Diabetes tipo 2 sintomática con marcada poliuria y polidipsia con una pérdida de peso superior al 10% durante los últimos 3 meses. -Aclaramiento de creatinina 193 seconds. -Symptomatic type 2 diabetes with marked polyuria and polydipsia with weight loss exceeding 10% during the last 3 months. -Creatinine clearance < 30 ml /min (MDRD) -Symptomatic coronary disease with at least one episode of pain and impaired coronary typical ST segment and / or cardiac enzyme changes in the last 12 months. -Coronary revascularization in the previous 12 months. -Patients who have received or are receiving other antithrombotic treatments in addition to aspirin in the previous month. -Patients with infectious disease, inflammatory, or neoplastic known. -Patients who have received any anti-inflammatory therapy in the last month, or other medications out of their own used for coronary artery disease. -Use of immunosuppressive drugs during the past 12 months. -Surgical procedures scheduled during the study period -Pregnant women or breastfeeding. -Women who at the time of inclusion in the study or just before the time of administration of drugs have a positive pregnancy test. -Patients who do not sign the informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: El objetivo principal del presente estudio es analizar, en pacientes diabéticos con enfermedad coronaria establecida de más de un año de evolución resistentes a la acción antiplaquetaria de la aspirina, si el tratamiento con alopurinol favorece el efecto antiplaquetario de la aspirina desde el punto de vista de su funcionalidad. Para ello, se analizará al inicio y al final del tratamiento con alopurinol la funcionalidad de las plaquetas de estos pacientes mediante el Sistema PFA-100. The main objective of this study is to analyze, in diabetic patients with established coronary heart disease over a year of evolution resistant to aspirin's antiplatelet action, whether treatment with allopurinol favors the antiplatelet effect of aspirin from the point of view functionality. To do this, an analysis at the beginning and end of treatment with allopurinol the functionality of platelets in these patients using the PFA-100 system;Secondary Objective: -Analizar el efecto del alopurinol sobre el mapa de expresión proteico plaquetario en pacientes diabéticos con enfermedad coronaria establecida resistentes a la aspirina -Determinar si el alopurinol modifica el secretoma de las plaquetas obtenidas de los pacientes incluidos en el estudio -Analizar si el tratamiento con alopurinol modifica el sistema NO/GMP cíclico en las plaquetas de los pacientes incluidos en el estudio -Analizar a nivel sistémico si el alopurinol ejerce efectos anti-inflamatorios beneficiosos para el paciente -To analyzethe effect of allopurinol on the platelet proteome in diabetic patients with stable coronary ischemic disease that are resistant to aspirin -To determine whether allopurinol modifies the platelet secretome of the included patients -To analyze whether allopurinol modifies the NO/cGMP system in platelets from the included patients -To analyze whether allopurinol exerts beneficial systemic anti-inflammatory effects in the studied patients;Primary end point(s): La variable princ | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Variables secundarias -Análisis de los cambios plasmáticos inducidos en diferentes marcadores inflamatorios tras el tratamiento con alopurinol (Proteína C reactiva de alta sensibilidad, IL-6,IL-10,IL-8,IL-12). -Análisis de los cambios inducidos en el proteoma plaquetario tras el tratamiento con dosis altas de alopurinol. -Análisis de los cambios inducidos en las proteínas liberadas al medio por las plaquetas (secretoma) tras el tratamiento con dosis altas de alopurinol. -Análisis del sistema NO/GMPC plaquetario en las plaquetas resistentes a aspirina antes y después del tratamiento con alopurinol. Secondary end points -Analysis of plasma changes induced in various inflammatory markers following treatment with allopurinol (Protein C reactive protein, IL-6, IL-10, IL-8, IL-12). -Analysis of induced changes in the platelet proteome after treatment with high doses of allopurinol. -Analysis of induced changes in proteins released into the medium by platelets (secretome) after treatment with high doses of allopurinol. -Analysis of the NO / platelet GMPC in platelets resistant to aspirin before and after treatment with allopurinol.;Timepoint(s) of evaluation of this end point: A las 6 semanas de tratamiento con alopurinol After 6 weeks with allopurinol treatment | — |
Countries
Spain
Contacts
Public ContactFundación Investigación Biomedica
Fundación Investigación Biomedica. Hospital Clinico San Carlos
Outcome results
None listed