Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2/PHASE3
72 participants
INTERVENTIONAL
2005-07-31
2010-11-30
Brief Summary
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Detailed Description
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In addition to enhanced Ang II production, hyperglycemia and diabetes also amplify the production of reactive oxygen species (ROS). ROS are associated with increased in LV remodeling and myocyte apoptosis. Furthermore, xanthine oxidase (XO), an important source of ROS in myocytes, is increased in a rat model of myocardial infarction and in diabetes. Thus, increased XO-mediated ROS production following MI may be especially damaging in diabetic patients where ROS production is already elevated. Interestingly, acute treatment with Allopurinol, an inhibitor of XO, improves cardiac function in heart failure and improves endothelial dysfunction in patients with type-2 diabetes.
To test our hypothesis the investigators will investigate the following aims in diabetic patients after acute MI:
Aim 1: Show that the progression of LV remodeling and dysfunction in diabetic patients will be attenuated to greater extent by AT1RB than by ACE inhibitor.
Aim 2: Show that the addition of XO inhibition results in further attenuation of LV remodeling than with AT1RB or ACE inhibitor alone.
Aim 3: Show that baseline and follow-up LV remodeling and dysfunction and inflammatory markers differ in diabetic and non-diabetic patients post-MI.
Conditions
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Keywords
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Study Design
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RANDOMIZED
FACTORIAL
TREATMENT
NONE
Study Groups
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Ramipril
The starting dose of Ramipril will be 2.5 mg once daily and rapidly titrated upward to 5 mg once daily after 5 days if systolic blood pressure is greater than 100 mmHg. After one month the patient will return to clinic for blood pressure check and will be titrated up to 10 mg once daily.
Ramipril
The starting dose of Ramipril will be 2.5 mg once daily and rapidly titrated upward to 5 mg once daily after 5 days if systolic blood pressure is greater than 100 mmHg. After one month the patient will return to clinic for blood pressure check and will be titrated up to 10 mg once daily.
Candesartan cilexetil
The starting dose of Candesartan cilexetil will be 4 mg or 8 mg once daily and doubled every 2 weeks, if systolic blood pressure is greater than 100 mmHg, to a maximum dose of 32 mg once daily. After one month the patient will return to clinic for blood pressure check and will be titrated up to 32 mg once daily.
Candesartan cilexetil
The starting dose of Candesartan cilexetil will be 4 mg or 8 mg once daily and doubled every 2 weeks, if systolic blood pressure is greater than 100 mmHg, to a maximum dose of 32 mg once daily. After one month the patient will return to clinic for blood pressure check and will be titrated up to 32 mg once daily.
Ramipril and Allopurinol
The starting dose of Ramipril will be 2.5 mg once daily and rapidly titrated upward to 5 mg once daily after 5 days if systolic blood pressure is greater than 100 mmHg. After one month the patient will return to clinic for blood pressure check and will be titrated up to 10 mg once daily. It is anticipated that the starting dose of each drug will be initiated in hospital and that the second dose will be implemented prior to discharge from the hospital. The starting dose of Allopurinol is 300 mg daily.
Ramipril
The starting dose of Ramipril will be 2.5 mg once daily and rapidly titrated upward to 5 mg once daily after 5 days if systolic blood pressure is greater than 100 mmHg. After one month the patient will return to clinic for blood pressure check and will be titrated up to 10 mg once daily.
Allopurinol
The starting dose of Allopurinol is 300 mg daily.
Candesartan cilexetil and Allopurinol
The starting dose of Candesartan cilexetil will be 4 mg or 8 mg once daily and doubled every 2 weeks, if systolic blood pressure is greater than 100 mmHg, to a maximum dose of 32 mg once daily. After one month the patient will return to clinic for blood pressure check and will be titrated up to 32 mg once daily. The starting dose of Allopurinol is 300 mg daily.
Candesartan cilexetil
The starting dose of Candesartan cilexetil will be 4 mg or 8 mg once daily and doubled every 2 weeks, if systolic blood pressure is greater than 100 mmHg, to a maximum dose of 32 mg once daily. After one month the patient will return to clinic for blood pressure check and will be titrated up to 32 mg once daily.
Allopurinol
The starting dose of Allopurinol is 300 mg daily.
Interventions
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Ramipril
The starting dose of Ramipril will be 2.5 mg once daily and rapidly titrated upward to 5 mg once daily after 5 days if systolic blood pressure is greater than 100 mmHg. After one month the patient will return to clinic for blood pressure check and will be titrated up to 10 mg once daily.
Candesartan cilexetil
The starting dose of Candesartan cilexetil will be 4 mg or 8 mg once daily and doubled every 2 weeks, if systolic blood pressure is greater than 100 mmHg, to a maximum dose of 32 mg once daily. After one month the patient will return to clinic for blood pressure check and will be titrated up to 32 mg once daily.
Allopurinol
The starting dose of Allopurinol is 300 mg daily.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. MI documented by increase in troponin \> 0.78 ng/ml or CKMB ≥ 3% of total CK
Patients who have Type-2 diabetes defined by any one of the following:
3. Confirmed (i.e., two or more readings) fasting blood glucose \>126mg/dl; or
4. Random glucose ≥200mg/dl; or
5. 2 hour glucose ≥200mg/dl following 75g of glucose; or
6. Current treatment with diet or oral agents directed at the control of hyperglycemia either alone or in combination with insulin; or
7. Current treatment with insulin with no prior history of diabetic ketoacidosis.
Exclusion Criteria
2. Class III or IV heart failure.
3. Cardiomyopathy (including hypertrophic and amyloidosis).
4. Congenital or pericardial diseases.
5. Intolerance to either ACE inhibitor, AT1-RB or allopurinol.
6. Renal failure with creatinine \> 2.5 mg/dl.
7. Renal artery stenosis.
8. Severe comorbidity such as liver disease or malignancy.
9. Pregnancy (negative pregnancy test and effective contraceptive methods are required prior to enrollment of females of childbearing potential (not post-menopausal or surgically sterilized).
10. Chronic steroid use.
11. Unable to understand or cooperate with protocol requirements.
12. Severe claustrophobia.
13. Presence of a pacemaker or non-removable hearing aid.
14. Presence of metal clips in the body.
21 Years
ALL
No
Sponsors
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National Heart, Lung, and Blood Institute (NHLBI)
NIH
AstraZeneca
INDUSTRY
University of Alabama at Birmingham
OTHER
Responsible Party
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Dr. Louis J. Dell'Italia
Principal Investigator
Principal Investigators
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Louis J. Dell'Italia, M.D.
Role: PRINCIPAL_INVESTIGATOR
University of Alabama at Birmingham
Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
Countries
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References
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Other Identifiers
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F040105007
Identifier Type: -
Identifier Source: org_study_id