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IRCT20190412043247N2 IRCT 2020-06-13 Zanjan University of Medical Sciences Assessment of Empagliflozin effects in coronary artery disease The assessment of Empagliflozin Effects in diabetic patients with coronary artery disease: The EMPA-CARD Randomized Clinical Trial 2020-06-29 anticipated 100 Complete https://irct.ir/trial/43333 interventional Randomization: Randomized, Blinding: Triple blinded, Placebo: Used, Assignment: Parallel, Purpose: Basic scienece, Randomization description: Stratified randomization and the randomization unit is also individual. the strata of randomization in this study are Gender, HbA1c and age. Randomization sequence will be created using Winpepi analysis software using 3 strata based on treatment group A or B for 100 patients, Blinding description: 1- Empagliflozin and placebo tablets have the same color, shape and package with the different code combination numbers (generated by random number table) for the 2 groups of A and B. 2- After enrollment , one code is assigned to each patient , which will be recognized by this code until the end of this study. 3- Patients, Researchers who receive information from patients, assess the outcomes and analyze the data of the study, Physicians and health care providers, The Data Supervision and Implementation Committee, which comprised of Zanjan University of Medical Sciences and Dr. Abidi Pharmaceutical Company will not aware that patients are receiving empagliflozin or placebo In such a way that all of the patients will be evaluated under the unique assigned code and the treatment group of A or B. The mentioned individuals will not know which code is empagliflozin or placebo. The only individual who knows about the patients assigned code and treatment group of A and B will be a consultant that has no communication to patients or the executive team members. 4 Condition 1: Diabetes Mellitus type 2. Condition 2: Coronary artery disease. Intervention 1: Intervention group: The 50 patients in the intervention group will be treated with Empagliflozine 10 mg daily for 6 months (made by Abidi Pharmaceutical Company). Patients will continue the routine medical cares as before the study such as periodic medical visits and laboratory tests. Intervention 2: Control group: The 50 patients will be placed in the second group, the Control group, and will be treated with Placebo for 6 months. Patients will continue the routine medical cares as before the study such as periodic medical visits and laboratory tests. Yes - There is a plan to make this available What will be shared: Patient's raw data will be storaged at online data repositories at the time study report. Study protocol will be reported in the form of a manuscript. When: After completing the study To whom: All individuals, legal, academic and non-academic Conditions: will be made available to others without limitation by providing rational reason. Where to obtain: By email to the corresponding How to obtain: By email or letter to the corresponding Comments: this study has substudies regarding some secondary outcomes including the echocardiographic findings, hematopoietic status, renal function, electrocardiographic findings and safety study.
public Hassan Ahangar
Gavazank Blvd, Ayatollah Mousavi Hospital
Zanjan Iran (Islamic Republic of) 6654541552 +98 911 151 2028 Ahanghar@zums.ac.ir Zanjan University of Medical Sciences scientific Hassan Ahangar
Gavazank Blvd, Ayatollah Mousavi Hospital
Zanjan Iran (Islamic Republic of) 2545451145 +98 911 151 2028 Ahanghar@zums.ac.ir Zanjan University of Medical Sciences Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Age between 40-75 year-old HbA1c between 6.5 to 9 Diabetes mellitus type 2 Under fix continues anti-diabetic treatment for at least 3 month BMI less than 40 Fixed Diet and physical activity Resting heart rate between 60 to 100 b/min Use of Aspirin 80 mg/Daily for at least 3 month prior to the beginning of study Glomerular filtration rate (GFR)>45 Documented known Coronary Artery Disease 40 years 75 years Both Pregnancy Heart Failure (NYHA class 3-4), Ejection Fraction <40% History of allergic reaction to SGLT2 inhibitors Drugs History of SGLT2 inhibitor Drugs usage Gastrointestinal malabsorbtion disease History of CABG, ACS, TIA,CVA or PCI during past 3 month History or presence of malignancy Severe HTN Anemia (Hb<10 g/dl) History of heart or lung transplant Major psychiatric disorders History of DKA Elevated liver enzymes >3 times upper normal limit Use of drugs prolonging QT interval Presence of Arrhythmia Electrolyte disorders Patients with Pace Maker Use of anti-coagulant or anti-platelet drugs for at least 3 months prior to the sampling Consumption of alcohol, Anti inflammatory drugs (except Aspirin) or Anti oxidant supplement Platelet count <100000/µl History of infection during 1 one month before sampling E11 I125.1 Type 2 diabetes mellitus Atherosclerotic heart disease of native coronary artery Treatment - Drugs Placebo Intervention group: The 50 patients in the intervention group will be treated with Empagliflozine 10 mg daily for 6 months (made by Abidi Pharmaceutical Company). Patients will continue the routine medical cares as before the study such as periodic medical visits and laboratory tests. Control group: The 50 patients will be placed in the second group, the Control group, and will be treated with Placebo for 6 months. Patients will continue the routine medical cares as before the study such as periodic medical visits and laboratory tests. Changes in Plasma Interleukin 6. Timepoint: At the beginning of the study and the end of week 26. Method of measurement: Plasma IL-6 Elisa Kits. Changes in oxidative stress (Changes in lymphocytic reactive oxygen species level). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Flow cytometry. Changes in oxidative stress (Changes in plasma levels of Malondialdehyde). Timepoint: At the beginning of study and the end of week 26. Method of measurement: colorimetric assay. Changes in oxidative stress (Changes in plasma carbonyl level). Timepoint: At the beginning of study and the end of week 26. Method of measurement: colorimetric assay. Changes in oxidative stress (Changes in total plasma antioxidant capacity). Timepoint: At the beginning of study and the end of week 26. Method of measurement: FRAP assay. Changes in oxidative stress (Changes in plasma reduced glutathione level). Timepoint: At the beginning of study and the end of week 26. Method of measurement: colorimetric assay. Changes in oxidative stress (Changes in plasma catalase enzyme activity). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Spectrophotometery. Changes in oxidative stress (Changes in plasma superoxide dismutase enzyme activity). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Spectrophotometery. Changes in plasma interleukin 1b. Timepoint: At the beginning of study and the end of week 26. Method of measurement: Interleukin 1b Elisa kit. Changes in platelet function. Timepoint: At the beginning of study and the end of week 26. Method of measurement: Flow cytometric measurement (CD62-P expression on platelet surface). Changes in serum total protein level. Timepoint: At the beginning of study and the end of week 26. Method of measurement: Spectrophotometry. Changes in Hematopoietic status (Changes in hemoglobin). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Complete blood count test. Changes in glycemic status (Homeostatic Model Assessment of Insulin Resistance). Timepoint: At the beginning of study and the end of week 26. Method of measurement: HOMA-IR= fasting insulin (mU/mL) x fasting glucose (mg/dL)/405. Changes in glycemic status (Changes in serum basal insulin level). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Chemiluminescence assay. Changes in glycemic status (Changes in HbA1c). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Enzymatic assay. Changes in glycemic status (Changes in blood fasting blood sugar). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Enzymatic assay. Changes in serum high sensitive C-reactive protein. Timepoint: At the beginning of study and the end of week 26. Method of measurement: Turbidimetric assay. Changes in high sensitivity-Troponin I level. Timepoint: At the beginning of study and the end of week 26. Method of measurement: Chemiluminescence assay. Changes in serum Pro-BNP level. Timepoint: At the beginning of study and the end of week 26. Method of measurement: Chemiluminescence assay. Changes in serum BNP level. Timepoint: At the beginning of study and the end of week 26. Method of measurement: Chemiluminescence assay. Changes in echocardiographic parameters (Left ventricular function). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Echocardiographic measurement. Changes in echocardiographic parameters (Right ventricular function). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Echocardiographic measurement. Changes in hematopoietic status (Changes in serum erythropoietin). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Serum Erythropoietin Elisa kit. Changes in hematopoietic status (Changes in Blood hematocrit). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Complete blood count test. Changes in renal function (Changes in urine albumin to creatinine ratio). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Photometry/ Enzymatic assays. Changes in renal function (Changes in urine micro albuminuria level). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Photometry assay. Changes in lipid profile (Changes in serum total cholesterol level). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Enzymatic assay. Changes in lipid profile (Changes in serum LDL cholesterol level). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Enzymatic assay. Changes in lipid profile (Changes in serum HDL cholesterol level). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Enzymatic assay. Changes in lipid profile (Changes in serum triglyceride level). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Enzymatic assay. Changes in electrocardiographic parameters (QT interval). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Electrocardiography. Changes in electrocardiographic parameters (ST segment deviation). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Electrocardiography. Changes in electrocardiographic parameters (T wave alternans). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Electrocardiography. Changes in electrocardiographic parameters (PR interval duration). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Electrocardiography. Changes in electrocardiographic parameters (QRS wave duration). Timepoint: At the beginning of study and the end of week 26. Method of measurement: Electrocardiography. Dr. Abidi Pharmaceutical Company Zanjan University of Medical Sciences Dr. Abidi Pharmaceutical Company Approved 2019-09-01 Ethics committee of Zanjan University of Medical Sciences Gavazang blv, Karmandan Quarter, Mousavi Hospital Zanjan Zanjan Iran (Islamic Republic of) Approved 2019-08-27 Ethics committee of Zanjan University of Medical Sciences Gavazang blv, Karmandan Quarter, Mousavi Hospital Zanjan Zanjan Iran (Islamic Republic of) Approved 2019-10-02 Ethics committee of Zanjan University of Medical Sciences Gavazang blv, Karmandan Quarter, Mousavi Hospital Zanjan Zanjan Iran (Islamic Republic of) Approved 2019-02-19 Ethics committee of Zanjan University of Medical Sciences Gavazang blv, Karmandan Quarter, Mousavi Hospital Zanjan Zanjan Iran (Islamic Republic of) Approved 2020-02-05 Ethics committee of Zanjan University of Medical Sciences Gavazang blv, Karmandan Quarter, Mousavi Hospital Zanjan Zanjan Iran (Islamic Republic of)