The Effects of Empagliflozin in diabetic patients with coronary artery disease
Design
A Parallel Drug-Placebo, triple blind, stratified Randomized trial of 100 patients (50 patients each group) with the follow up period of 6 months.
Settings and conduct
This will be a Triple blind (outcome assessor and care provider, patients and Data Supervision Committee and Data Analyzer) trial in Zanjan,Iran. patients will be divided into 2 groups and will receive empagliflozin tablet 10 mg or placebo daily for 6 months. Blood sampling, ECG, echocardiogram will be obtained at the beginning of the study and the end of 6 months.
Participants/Inclusion and exclusion criteria
The study population included patients with type 2 diabetes with coronary artery disease. All of patients are treated with Aspirin 80mg/Daily and anti diabetic drugs for at least 3 month prior to the beginning of study and will have acceptable hemodynamic function.
exclusion criteria:
Pregnancy,heart failure or arrhythmia,moderate to severe liver,kidney,hematologic or malabsorpsion disease,psychological and electrolyte imbalance,use of alcohol,anti-inflammatory or antioxidant drugs,history of infection during last 1 month and major cardiac or cerebral accidents during 1 year or cardio-pulmonary surgeries and history of usage or allergy to SGLT2 inhibitors drugs.
Intervention groups
Population will be comprised of patients with type 2 diabetes with known coronary artery disease that will be divided into 2 groups of 50 patients.
1- Drug group: will be treated with empagliflozin tablet (10 mg/Daily).
2- Control group: will be treated with placebo tablets.
Main outcome variables
1) Changes in plasma Interleukin 6
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20190412043247N2
Registration date:2020-06-13, 1399/03/24
Registration timing:prospective
Last update:2020-06-13, 1399/03/24
Update count:0
Registration date
2020-06-13, 1399/03/24
Registrant information
Name
Hassan Ahangar
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 24 3313 0001
Email address
ahanghar@zums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2020-06-29, 1399/04/09
Expected recruitment end date
2020-09-30, 1399/07/09
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
The assessment of Empagliflozin Effects in diabetic patients with coronary artery disease: The EMPA-CARD Randomized Clinical Trial
Public title
Assessment of Empagliflozin effects in coronary artery disease
Purpose
Basic scienece
Inclusion/Exclusion criteria
Inclusion criteria:
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
Exclusion criteria:
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
Age
From 40 years old to 75 years old
Gender
Both
Phase
4
Groups that have been masked
Participant
Care provider
Investigator
Outcome assessor
Data analyser
Data and Safety Monitoring Board
Sample size
Target sample size:
100
Randomization (investigator's opinion)
Randomized
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 (investigator's opinion)
Triple blinded
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.
Placebo
Used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics committee of Zanjan University of Medical Sciences
Street address
Gavazang blv, Karmandan Quarter, Mousavi Hospital
City
Zanjan
Province
Zanjan
Postal code
4515613191
Approval date
2019-09-01, 1398/06/10
Ethics committee reference number
IR.ZUMS.REC.1398.279
2
Ethics committee
Name of ethics committee
Ethics committee of Zanjan University of Medical Sciences
Street address
Gavazang blv, Karmandan Quarter, Mousavi Hospital
City
Zanjan
Province
Zanjan
Postal code
4515613191
Approval date
2019-08-27, 1398/06/05
Ethics committee reference number
IR.ZUMS.REC.1398.278
3
Ethics committee
Name of ethics committee
Ethics committee of Zanjan University of Medical Sciences
Street address
Gavazang blv, Karmandan Quarter, Mousavi Hospital
City
Zanjan
Province
Zanjan
Postal code
4515613191
Approval date
2019-10-02, 1398/07/10
Ethics committee reference number
IR.ZUMS.REC.1398.289
4
Ethics committee
Name of ethics committee
Ethics committee of Zanjan University of Medical Sciences
Street address
Gavazang blv, Karmandan Quarter, Mousavi Hospital
City
Zanjan
Province
Zanjan
Postal code
4515613191
Approval date
2019-02-19, 1397/11/30
Ethics committee reference number
IR.ZUMS.REC.1397.347
5
Ethics committee
Name of ethics committee
Ethics committee of Zanjan University of Medical Sciences
Street address
Gavazang blv, Karmandan Quarter, Mousavi Hospital
City
Zanjan
Province
Zanjan
Postal code
4515613191
Approval date
2020-02-05, 1398/11/16
Ethics committee reference number
IR.ZUMS.REC.1398.444
Health conditions studied
1
Description of health condition studied
Diabetes Mellitus type 2
ICD-10 code
E11
ICD-10 code description
Type 2 diabetes mellitus
2
Description of health condition studied
Coronary artery disease
ICD-10 code
I125.1
ICD-10 code description
Atherosclerotic heart disease of native coronary artery
Primary outcomes
1
Description
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
Secondary outcomes
1
Description
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
2
Description
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
3
Description
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
4
Description
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
5
Description
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
6
Description
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
7
Description
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
8
Description
Changes in plasma interleukin 1b
Timepoint
At the beginning of study and the end of week 26
Method of measurement
Interleukin 1b Elisa kit
9
Description
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)
10
Description
Changes in serum total protein level
Timepoint
At the beginning of study and the end of week 26
Method of measurement
Spectrophotometry
11
Description
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
12
Description
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
13
Description
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
14
Description
Changes in glycemic status (Changes in HbA1c)
Timepoint
At the beginning of study and the end of week 26
Method of measurement
Enzymatic assay
15
Description
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
16
Description
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
17
Description
Changes in high sensitivity-Troponin I level
Timepoint
At the beginning of study and the end of week 26
Method of measurement
Chemiluminescence assay
18
Description
Changes in serum Pro-BNP level
Timepoint
At the beginning of study and the end of week 26
Method of measurement
Chemiluminescence assay
19
Description
Changes in serum BNP level
Timepoint
At the beginning of study and the end of week 26
Method of measurement
Chemiluminescence assay
20
Description
Changes in echocardiographic parameters (Left ventricular function)
Timepoint
At the beginning of study and the end of week 26
Method of measurement
Echocardiographic measurement
21
Description
Changes in echocardiographic parameters (Right ventricular function)
Timepoint
At the beginning of study and the end of week 26
Method of measurement
Echocardiographic measurement
22
Description
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
23
Description
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
24
Description
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
25
Description
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
26
Description
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
27
Description
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
28
Description
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
29
Description
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
30
Description
Changes in electrocardiographic parameters (QT interval)
Timepoint
At the beginning of study and the end of week 26
Method of measurement
Electrocardiography
31
Description
Changes in electrocardiographic parameters (ST segment deviation)
Timepoint
At the beginning of study and the end of week 26
Method of measurement
Electrocardiography
32
Description
Changes in electrocardiographic parameters (T wave alternans)
Timepoint
At the beginning of study and the end of week 26
Method of measurement
Electrocardiography
33
Description
Changes in electrocardiographic parameters (PR interval duration)
Timepoint
At the beginning of study and the end of week 26
Method of measurement
Electrocardiography
34
Description
Changes in electrocardiographic parameters (QRS wave duration)
Timepoint
At the beginning of study and the end of week 26
Method of measurement
Electrocardiography
Intervention groups
1
Description
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.
Category
Treatment - Drugs
2
Description
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.
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Zanjan University of Medical Sciences
Proportion provided by this source
50
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
2
Sponsor
Name of organization / entity
Dr. Abidi Pharmaceutical Company
Full name of responsible person
Seyed Amir Razavian
Street address
No 72, Abidi Blv, Lashkari Expressway
City
Tehran
Province
Tehran
Postal code
13897-76363
Phone
+98 21 4452 2451
Fax
+98 21 4450 4787
Email
info@doctor-abidi.com
Web page address
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Dr. Abidi Pharmaceutical Company
Proportion provided by this source
50
Public or private sector
Private
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Industry
Person responsible for general inquiries
Contact
Name of organization / entity
Zanjan University of Medical Sciences
Full name of responsible person
Hassan Ahangar
Position
Assistant Proffessor
Latest degree
Subspecialist
Other areas of specialty/work
Cardiology
Street address
Gavazank Blvd, Ayatollah Mousavi Hospital
City
Zanjan
Province
Zanjan
Postal code
6654541552
Phone
+98 911 151 2028
Email
Ahanghar@zums.ac.ir
Person responsible for scientific inquiries
Contact
Name of organization / entity
Zanjan University of Medical Sciences
Full name of responsible person
Hassan Ahangar
Position
Assistant Proffessor
Latest degree
Subspecialist
Other areas of specialty/work
Cardiology
Street address
Gavazank Blvd, Ayatollah Mousavi Hospital
City
Zanjan
Province
Zanjan
Postal code
2545451145
Phone
+98 911 151 2028
Email
Ahanghar@zums.ac.ir
Person responsible for updating data
Contact
Name of organization / entity
Zanjan University of Medical Sciences
Full name of responsible person
Sepehr Gohari
Position
Medical student
Latest degree
A Level or less
Other areas of specialty/work
General Practitioner
Street address
School of Medicine, Mahdavi Blv, Karmandan Quarter
City
Zanjan
Province
Zanjan
Postal code
4513956111
Phone
+98 912 464 7838
Email
sepehr_goharibdb@yahoo.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
Yes - There is a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Yes - There is a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available
Title and more details about the data/document
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 the data will become available and for how long
After completing the study
To whom data/document is available
All individuals, legal, academic and non-academic
Under which criteria data/document could be used
will be made available to others without limitation by providing rational reason.
From where data/document is obtainable
By email to the corresponding
What processes are involved for a request to access data/document
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.