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P3: Impact of Diabetes on Left Ventricular Remodeling

Sponsor
University of Alabama at Birmingham (Other)
Overall Status
Completed
CT.gov ID
NCT01052272
Collaborator
National Heart, Lung, and Blood Institute (NHLBI) (NIH), AstraZeneca (Industry)
72
Enrollment
1
Location
4
Arms
64
Duration (Months)
1.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators hypothesize that in patients with diabetes and acute myocardial infarction (MI), Ang II type-1 receptor blockade (AT1RB) attenuates left ventricle (LV) remodeling to a greater extent than angiotensin converting enzyme (ACE) inhibitor therapy and that the addition of xanthine oxidase (XO) inhibitor, Allopurinol, results in further improvement in LV remodeling and function in the follow-up phase after MI.

Condition or Disease Intervention/Treatment Phase
Phase 2/Phase 3

Detailed Description

Following myocardial infarction (MI), the incidence of heart failure and mortality rates are approximately two-fold higher in patients with diabetes compared to those without diabetes. This increased risk for heart failure and mortality appears to be refractory to currently available treatments such as angiotensin converting enzyme (ACE) inhibitors, despite the effectiveness of such treatments in reducing overall morbidity and mortality following MI. Hyperglycemia stimulates cardiomyocyte angiotensin II (Ang II) formation, which has been implicated in increased myocyte cell death in diabetes. Furthermore, in humans, chymase is the predominant pathway of Ang II formation and this pathway of Ang II production is not blocked by ACE inhibition. Therefore, in diabetes where Ang II levels may already be elevated due to hyperglycemia the increase in Ang II formation associated with left ventricular (LV) remodeling continued Ang II formation from chymase could be particularly detrimental.

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
72 participants
Allocation:
Randomized
Intervention Model:
Factorial Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 2/3 Study of Effect of AT1RB Versus ACE Inhibitor in Addition to XO Inhibitor on Progression of LV Remodeling and Dysfunction in Diabetic Patients With Acute MI.
Study Start Date :
Jul 1, 2005
Actual Primary Completion Date :
Nov 1, 2010
Actual Study Completion Date :
Nov 1, 2010

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: 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.

Drug: 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.
Other Names:
  • Altace

    		•
    Active Comparator: 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.

    Drug: 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.
    Other Names:
  • Atacand

    		•
    Active Comparator: 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.

    Drug: 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.
    Other Names:
  • Altace

    • Drug: Allopurinol
    The starting dose of Allopurinol is 300 mg daily.
    Other Names:
  • Altace

    		•
    Active Comparator: 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.

    Drug: 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.
    Other Names:
  • Atacand

    • Drug: Allopurinol
    The starting dose of Allopurinol is 300 mg daily.
    Other Names:
  • Altace

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Left Ventricular End Diastolic Volume Indexed to Body Surface Area (LVEDV/BSA) [5 visits per Participant over 2 years (about every 6 months)]

      LVEDV/BSA: As an indicator of heart size, the blood volume of the heart is related to the body size. The relation of heart blood volume to body size is more accurate in determining pathology because larger people require a larger heart blood volume. The values that are too high or too low indicate a diseased myocardium. This is a measure of LV Diastolic Function. Since some visits did not occur at the scheduled 6 month intervals, the results have been divided into 3-month visit intervals.

    2. Left Ventricular End-Diastolic Radius to Wall Thickness (LVED Radius/Wall Thickness) [5 visits per Participant over 2 years (about every 6 months)]

      LVED Radius/Wall thickness As an indicator of heart muscle mass and heart volume chamber diameter, the end-diastolic radius indexed to end diastolic wall thickness determines whether there is an adequate amount of heart muscle to pump the heart blood volume obtained from a two-dimensional analysis. The values that are too high or too low indicate a diseased myocardium. This is a measure of LV Geometry. Since some visits did not occur at the scheduled 6 month intervals, the results have been divided into 3-month visit intervals for reporting purposes.

    3. Left Ventricular End-diastolic Mass Indexed to Left Ventricular End-diastolic Volume (LVED Mass/LVEDV) [5 visits per Participant over 2 years (about every 6 months)]

      LVED Mass/LVEDV: As an indicator of heart muscle mass and heart blood volume, the mass indexed to end diastolic volume determines whether there is an adequate amount of heart muscle to pump the heart blood volume obtained from a three-dimensional analysis. The values that are too high or too low indicate a diseased myocardium. This is a measure of LV Geometry. Since some visits did not occur at the scheduled 6 month intervals, the results have been divided into 3-month visit intervals for reporting purposes.

    4. Left Ventricular Ejection Fraction (LVEF) [5 visits per Participant over 2 years (about every 6 months)]

      LVEF is a calculation of heart pump function determined from the volume after complete filling minus the volume after complete contraction divided by the volume after complete filling. A value of 55% or greater is normal. This is a measure of LV Systolic Function. Since some visits did not occur at the scheduled 6 month intervals, the results have been divided into 3-month visit intervals for reporting purposes

    5. Left Ventricular End Systolic Volume Indexed to Body Surface Area (LVESV/BSA) [5 visits per Participant over 2 years (about every 6 months)]

      LVESV/BSA: The end systolic volume is the blood volume of the heart at the end of contraction and is an index of the pump function of the heart. This relation to body size is more accurate in determining pathology because larger people require a larger heart blood volume. The values that are too high or too low indicate a diseased myocardium. This is a measure of LV Systolic Function. Since some visits did not occur at the scheduled 6 month intervals, the results have been divided into 3-month visit intervals.

    6. LV End Systolic Maximum Shortening (LVES Max Shortening) [5 visits per Participant over 2 years (about every 6 months)]

      By identifying three points in three different planes in the heart muscle, the maximum shortening is the average of the difference between the distance between these three points at the end of filling of the heart and the end of contraction divided by the length at the end of filling times 100. The maximum shortening is a three dimensional analysis. The higher values indicate a healthy heart. This is a measure of LV Systolic Function. Since some visits did not occur at the scheduled 6 month intervals, the results have been divided into 3-month visit intervals for reporting purposes.

    7. Peak Early Filling Rate Normalized to EDV [5 visits per Participant over 2 years (about every 6 months)]

      The Peak Early Filling Rate Normalized to EDV is calculated from the slope of the volume during the early filling of the heart with respect to time. The higher values indicate a very healthy heart muscle and lower values are indicative of a very stiff muscle. This is a measure of LV Diastolic Function. Since some visits did not occur at the scheduled 6 month intervals, the results have been divided into 3-month visit intervals for reporting purposes.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    21 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. 21 years old or older

    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:

    1. Confirmed (i.e., two or more readings) fasting blood glucose >126mg/dl; or

    2. Random glucose ≥200mg/dl; or

    3. 2 hour glucose ≥200mg/dl following 75g of glucose; or

    4. Current treatment with diet or oral agents directed at the control of hyperglycemia either alone or in combination with insulin; or

    5. Current treatment with insulin with no prior history of diabetic ketoacidosis.

    Exclusion Criteria:

    1. Type-1 diabetes.

    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35294-2180

    Sponsors and Collaborators

    • University of Alabama at Birmingham
    • National Heart, Lung, and Blood Institute (NHLBI)
    • AstraZeneca

    Investigators

    • Principal Investigator: Louis J. Dell'Italia, M.D., University of Alabama at Birmingham

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Dr. Louis J. Dell'Italia, Principal Investigator, University of Alabama at Birmingham
    ClinicalTrials.gov Identifier:
    NCT01052272
    Other Study ID Numbers:
    • F040105007
    First Posted:
    Jan 20, 2010
    Last Update Posted:
    Dec 17, 2012
    Last Verified:
    Nov 1, 2012
    Keywords provided by Dr. Louis J. Dell'Italia, Principal Investigator, University of Alabama at Birmingham
    Diabetes
    Acute MI
    Ang II type-1 receptor blockade (AT1RB)
    LV remodeling
    ACE inhibitor therapy
    XO inhibitor, Allopurinol
    Systolic dysfunction
    Diastolic dysfunction
    LV dimensions
    Cardiac MRI
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Allopurinol
    Candesartan
    Candesartan cilexetil
    Ramipril

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Ramipril Candesartan Cilexetil Ramipril and Allopurinol Candesartan Cilexetil and Allopurinol
    Arm/Group Description 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. 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 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. 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.
    Period Title: Overall Study
    STARTED 18 18 18 18
    COMPLETED 13 11 10 11
    NOT COMPLETED 5 7 8 7

    Baseline Characteristics

    Arm/Group Title Ramipril Candesartan Cilexetil Ramipril and Allopurinol Candesartan Cilexetil and Allopurinol Total
    Arm/Group Description 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. 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 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. 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. Total of all reporting groups
    Overall Participants 18 18 18 18 72
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    12
    66.7%
    12
    66.7%
    11
    61.1%
    10
    55.6%
    45
    62.5%
    >=65 years
    6
    33.3%
    6
    33.3%
    7
    38.9%
    8
    44.4%
    27
    37.5%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    58.17
    (10.61)
    60.94
    (11.27)
    60.67
    (10.57)
    62
    (10.86)
    60.44
    (10.69)
    Sex: Female, Male (Count of Participants)
    Female
    2
    11.1%
    3
    16.7%
    8
    44.4%
    3
    16.7%
    16
    22.2%
    Male
    16
    88.9%
    15
    83.3%
    10
    55.6%
    15
    83.3%
    56
    77.8%
    Region of Enrollment (participants) [Number]
    United States
    18
    100%
    18
    100%
    18
    100%
    18
    100%
    72
    100%

    Outcome Measures

    1. Primary Outcome
    Title Left Ventricular End Diastolic Volume Indexed to Body Surface Area (LVEDV/BSA)
    Description LVEDV/BSA: As an indicator of heart size, the blood volume of the heart is related to the body size. The relation of heart blood volume to body size is more accurate in determining pathology because larger people require a larger heart blood volume. The values that are too high or too low indicate a diseased myocardium. This is a measure of LV Diastolic Function. Since some visits did not occur at the scheduled 6 month intervals, the results have been divided into 3-month visit intervals.
    Time Frame 5 visits per Participant over 2 years (about every 6 months)

    Outcome Measure Data

    Analysis Population Description
    intent to treat
    Arm/Group Title Ramipril Candesartan Cilexetil Ramipril and Allopurinol Candesartan Cilexetil and Allopurinol
    Arm/Group Description 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. 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 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. 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.
    Measure Participants 18 18 18 18
    Month 0 (n=17,17,18,18)
    73.03
    (20.34)
    78.06
    (18.4)
    78.52
    (19.31)
    79.03
    (21.39)
    Month 6(n=14,11,11,12)
    74.10
    (15.53)
    78.60
    (24.30)
    86.13
    (24.14)
    78.01
    (14.49)
    Month 9(n=1,2,0,0)
    73.23
    (NA)
    93.57
    (18.48)
    NA
    (NA)
    NA
    (NA)
    Month12(n=12,11,11,11)
    75.34
    (20.30)
    85.44
    (20.87)
    83.95
    (20.69)
    79.75
    (19.9)
    Month 15(n=3,2,1,1)
    81.19
    (5.96)
    90.20
    (13.24)
    108.25
    (NA)
    63.1
    (NA)
    Month 18(n=10,12,8,8)
    75.28
    (14.48)
    82.74
    (23.09)
    67.96
    (12.86)
    84.95
    (17.55)
    Month 21(n=3,0,0,1)
    71.99
    (28.13)
    NA
    (NA)
    NA
    (NA)
    75.27
    (NA)
    Month 24 (n=11,9,8,10)
    70.46
    (17.17)
    84.28
    (23.17)
    71.63
    (8.59)
    79.72
    (15.11)
    Month 27 (n=1,1,0,1)
    48.68
    (NA)
    76.65
    (NA)
    NA
    (NA)
    75.05
    (NA)
    2. Primary Outcome
    Title Left Ventricular End-Diastolic Radius to Wall Thickness (LVED Radius/Wall Thickness)
    Description LVED Radius/Wall thickness As an indicator of heart muscle mass and heart volume chamber diameter, the end-diastolic radius indexed to end diastolic wall thickness determines whether there is an adequate amount of heart muscle to pump the heart blood volume obtained from a two-dimensional analysis. The values that are too high or too low indicate a diseased myocardium. This is a measure of LV Geometry. Since some visits did not occur at the scheduled 6 month intervals, the results have been divided into 3-month visit intervals for reporting purposes.
    Time Frame 5 visits per Participant over 2 years (about every 6 months)

    Outcome Measure Data

    Analysis Population Description
    intent to treat
    Arm/Group Title Ramipril Candesartan Cilexetil Ramipril and Allopurinol Candesartan Cilexetil and Allopurinol
    Arm/Group Description 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. 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 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. 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.
    Measure Participants 18 18 18 18
    Month 0 (n=17,17,18,18)
    3.23
    (0.77)
    3.14
    (0.79)
    3.57
    (0.98)
    3.45
    (0.61)
    Month 6(n=14,11,11,12)
    3.32
    (0.70)
    3.39
    (0.44)
    4.04
    (0.75)
    3.63
    (0.61)
    Month 9(n=1,2,0,0)
    3.42
    (NA)
    4.14
    (0.84)
    NA
    (NA)
    NA
    (NA)
    Month 12(n=12,11,11,11)
    3.43
    (0.71)
    3.68
    (0.68)
    4.01
    (0.71)
    3.42
    (0.47)
    Month 15(n=3,2,1,1)
    3.44
    (0.56)
    4.10
    (1.10)
    4.57
    (NA)
    3.90
    (NA)
    Month 18(n=10,12,8,8)
    3.60
    (0.69)
    3.71
    (0.76)
    3.60
    (0.55)
    3.56
    (0.48)
    Month 21(n=3,0,0,1)
    2.92
    (0.43)
    NA
    (NA)
    NA
    (NA)
    4.24
    (NA)
    Month 24 (n=11,9,8,10)
    3.46
    (0.74)
    3.58
    (0.69)
    3.61
    (0.57)
    3.56
    (0.37)
    Month 27 (n=1,1,0,1)
    3.12
    (NA)
    4.04
    (NA)
    NA
    (NA)
    4.29
    (NA)
    3. Primary Outcome
    Title Left Ventricular End-diastolic Mass Indexed to Left Ventricular End-diastolic Volume (LVED Mass/LVEDV)
    Description LVED Mass/LVEDV: As an indicator of heart muscle mass and heart blood volume, the mass indexed to end diastolic volume determines whether there is an adequate amount of heart muscle to pump the heart blood volume obtained from a three-dimensional analysis. The values that are too high or too low indicate a diseased myocardium. This is a measure of LV Geometry. Since some visits did not occur at the scheduled 6 month intervals, the results have been divided into 3-month visit intervals for reporting purposes.
    Time Frame 5 visits per Participant over 2 years (about every 6 months)

    Outcome Measure Data

    Analysis Population Description
    intent to treat
    Arm/Group Title Ramipril Candesartan Cilexetil Ramipril and Allopurinol Candesartan Cilexetil and Allopurinol
    Arm/Group Description 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. 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 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. 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.
    Measure Participants 18 18 18 18
    Month 0 (n=17,17,18,18)
    0.92
    (0.25)
    0.95
    (0.27)
    0.86
    (0.26)
    0.87
    (0.13)
    Month 6(n=14,11,11,12)
    0.87
    (0.18)
    0.83
    (0.13)
    0.71
    (0.17)
    0.82
    (0.12)
    Month 9(n=1,2,0,0)
    0.75
    (NA)
    0.67
    (0.11)
    NA
    (NA)
    NA
    (NA)
    Month 12(n=12,11,11,11)
    0.84
    (0.18)
    0.78
    (0.19)
    0.72
    (0.15)
    0.86
    (0.13)
    Month 15(n=3,2,1,1)
    0.81
    (0.16)
    0.70
    (0.18)
    0.57
    (NA)
    0.68
    (NA)
    Month 18(n=10,12,8,8)
    0.79
    (0.16)
    0.79
    (0.22)
    0.83
    (0.16)
    0.80
    (0.12)
    Month 21(n=3,0,0,1)
    0.95
    (0.25)
    NA
    (NA)
    NA
    (NA)
    0.69
    (NA)
    Month 24 (n=11,9,8,10)
    0.84
    (0.18)
    0.80
    (0.20)
    0.80
    (0.14)
    0.82
    (0.08)
    Month 27 (n=1,1,0,1)
    0.93
    (NA)
    0.64
    (NA)
    NA
    (NA)
    0.69
    (NA)
    4. Primary Outcome
    Title Left Ventricular Ejection Fraction (LVEF)
    Description LVEF is a calculation of heart pump function determined from the volume after complete filling minus the volume after complete contraction divided by the volume after complete filling. A value of 55% or greater is normal. This is a measure of LV Systolic Function. Since some visits did not occur at the scheduled 6 month intervals, the results have been divided into 3-month visit intervals for reporting purposes
    Time Frame 5 visits per Participant over 2 years (about every 6 months)

    Outcome Measure Data

    Analysis Population Description
    intent to treat
    Arm/Group Title Ramipril Candesartan Cilexetil Ramipril and Allopurinol Candesartan Cilexetil and Allopurinol
    Arm/Group Description 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. 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 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. 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.
    Measure Participants 18 18 18 18
    Month 0 (n=17,17,18,18)
    52.19
    (10.65)
    56.36
    (12.34)
    53.37
    (10.01)
    52.68
    (13.90)
    Month 6(n=14,11,11,12)
    54.20
    (10.27)
    56.82
    (10.81)
    52.80
    (15.66)
    57.28
    (9.17)
    Month 9(n=1,2,0,0)
    64.98
    (NA)
    42.62
    (1.95)
    NA
    (NA)
    NA
    (NA)
    Month 12(n=12,11,11,11)
    52.76
    (9.94)
    52.37
    (11.41)
    51.74
    (15.54)
    56.11
    (11.33)
    Month 15(n=3,2,1,1)
    52.13
    (14.08)
    39.88
    (2.76)
    34.89
    (NA)
    54.46
    (NA)
    Month 18(n=10,12,8,8)
    55.02
    (13.24)
    56.33
    (10.26)
    54.05
    (9.96)
    57.82
    (10.97)
    Month 21(n=3,0,0,1)
    51.27
    (1.73)
    NA
    (NA)
    NA
    (NA)
    56.17
    (NA)
    Month 24 (n=11,9,8,10)
    57.18
    (9.79)
    51.70
    (10.02)
    55.59
    (9.47)
    55.79
    (10.53)
    Month 27 (n=1,1,0,1)
    50.73
    (NA)
    54.17
    (NA)
    NA
    (NA)
    54.40
    (NA)
    5. Primary Outcome
    Title Left Ventricular End Systolic Volume Indexed to Body Surface Area (LVESV/BSA)
    Description LVESV/BSA: The end systolic volume is the blood volume of the heart at the end of contraction and is an index of the pump function of the heart. This relation to body size is more accurate in determining pathology because larger people require a larger heart blood volume. The values that are too high or too low indicate a diseased myocardium. This is a measure of LV Systolic Function. Since some visits did not occur at the scheduled 6 month intervals, the results have been divided into 3-month visit intervals.
    Time Frame 5 visits per Participant over 2 years (about every 6 months)

    Outcome Measure Data

    Analysis Population Description
    intent to treat
    Arm/Group Title Ramipril Candesartan Cilexetil Ramipril and Allopurinol Candesartan Cilexetil and Allopurinol
    Arm/Group Description 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. 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 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. 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.
    Measure Participants 18 18 18 18
    Month 0 (n=17,17,18,18)
    36.20
    (16.64)
    35.26
    (16.08)
    37.91
    (16.63)
    39.49
    (21.97)
    Month 6(n=14,11,11,12)
    34.77
    (13.56)
    35.26
    (18.36)
    42.88
    (25.33)
    34.15
    (12.80)
    Month 9(n=1,2,0,0)
    25.64
    (NA)
    53.87
    (12.43)
    NA
    (NA)
    NA
    (NA)
    Month 12(n=12,11,11,11)
    36.82
    (15.88)
    42.27
    (19.83)
    42.34
    (25.18)
    36.07
    (16.24)
    Month 15(n=3,2,1,1)
    39.42
    (14.05)
    54.04
    (5.47)
    70.48
    (NA)
    28.74
    (NA)
    Month 18(n=10,12,8,8)
    35.30
    (17.21)
    37.76
    (18.48)
    30.39
    (4.61)
    37.18
    (15.95)
    Month 21(n=3,0,0,1)
    35.23
    (14.52)
    NA
    (NA)
    NA
    (NA)
    32.99
    (NA)
    Month 24 (n=11,9,8,10)
    31.17
    (14.47)
    41.72
    (18.48)
    31.56
    (6.52)
    35.99
    (13.65)
    Month 27 (n=1,1,0,1)
    23.98
    (NA)
    35.13
    (NA)
    NA
    (NA)
    34.22
    (NA)
    6. Primary Outcome
    Title LV End Systolic Maximum Shortening (LVES Max Shortening)
    Description By identifying three points in three different planes in the heart muscle, the maximum shortening is the average of the difference between the distance between these three points at the end of filling of the heart and the end of contraction divided by the length at the end of filling times 100. The maximum shortening is a three dimensional analysis. The higher values indicate a healthy heart. This is a measure of LV Systolic Function. Since some visits did not occur at the scheduled 6 month intervals, the results have been divided into 3-month visit intervals for reporting purposes.
    Time Frame 5 visits per Participant over 2 years (about every 6 months)

    Outcome Measure Data

    Analysis Population Description
    intent to treat
    Arm/Group Title Ramipril Candesartan Cilexetil Ramipril and Allopurinol Candesartan Cilexetil and Allopurinol
    Arm/Group Description 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. 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 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. 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.
    Measure Participants 18 18 18 18
    Month 0 (n=17,17,17,18)
    15.81
    (3.56)
    16.68
    (3.12)
    15.84
    (2.70)
    16.00
    (2.77)
    Month 6(n=14,11,10,12)
    16.88
    (1.90)
    17.50
    (2.07)
    18.72
    (2.4)
    18.50
    (2.0)
    Month 9(n=1,2,0,0)
    18.43
    (NA)
    19.08
    (2.78)
    NA
    (NA)
    NA
    (NA)
    Month 12(n=11,11,10,10)
    14.57
    (2.91)
    17.13
    (1.94)
    17.96
    (1.68)
    18.51
    (2.41)
    Month 15(n=3,2,1,1)
    17.06
    (1.83)
    16.28
    (2.42)
    14.22
    (NA)
    16.36
    (NA)
    Month 18(n=10,12,7,8)
    17.26
    (1.46)
    17.55
    (1.62)
    17.46
    (1.19)
    17.52
    (1.6)
    Month 21(n=3,0,0,1)
    16.68
    (1.27)
    NA
    (NA)
    NA
    (NA)
    17.89
    (NA)
    Month 24 (n=11,9,8,10)
    15.67
    (3.36)
    16.62
    (1.32)
    17.52
    (1.17)
    17.85
    (1.37)
    Month 27 (n=1,1,0,1)
    13.70
    (NA)
    20.38
    (NA)
    NA
    (NA)
    16.59
    (NA)
    7. Primary Outcome
    Title Peak Early Filling Rate Normalized to EDV
    Description The Peak Early Filling Rate Normalized to EDV is calculated from the slope of the volume during the early filling of the heart with respect to time. The higher values indicate a very healthy heart muscle and lower values are indicative of a very stiff muscle. This is a measure of LV Diastolic Function. Since some visits did not occur at the scheduled 6 month intervals, the results have been divided into 3-month visit intervals for reporting purposes.
    Time Frame 5 visits per Participant over 2 years (about every 6 months)

    Outcome Measure Data

    Analysis Population Description
    intent to treat
    Arm/Group Title Ramipril Candesartan Cilexetil Ramipril and Allopurinol Candesartan Cilexetil and Allopurinol
    Arm/Group Description 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. 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 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. 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.
    Measure Participants 18 18 18 18
    Month 0 (n=17,17,18,18)
    1.93
    (0.69)
    2.01
    (0.76)
    2.11
    (0.56)
    2.0
    (0.74)
    Month 6(n=14,11,11,12)
    1.74
    (0.77)
    2.02
    (0.81)
    2.03
    (0.95)
    1.98
    (0.73)
    Month 9(n=1,2,0,0)
    2.50
    (NA)
    1.13
    (0.83)
    NA
    (NA)
    NA
    (NA)
    Month 12(n=12,11,11,11)
    1.80
    (0.60)
    1.90
    (0.71)
    1.93
    (0.45)
    1.77
    (0.83)
    Month 15(n=3,2,1,1)
    2.02
    (1.09)
    1.48
    (0.58)
    1.56
    (NA)
    2.28
    (NA)
    Month 18(n=10,12,8,8)
    1.91
    (0.52)
    1.93
    (0.84)
    1.89
    (0.78)
    2.05
    (0.59)
    Month 21(n=3,0,0,1)
    1.69
    (0.42)
    NA
    (NA)
    NA
    (NA)
    2.50
    (NA)
    Month 24 (n=11,9,8,10)
    2.05
    (0.81)
    1.65
    (0.55)
    1.88
    (0.50)
    1.82
    (0.78)
    Month 27 (n=1,1,0,1)
    1.34
    (NA)
    1.10
    (NA)
    NA
    (NA)
    2.15
    (NA)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Ramipril Candesartan Cilexetil Ramipril and Allopurinol Candesartan Cilexetil and Allopurinol
    Arm/Group Description 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. 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 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. 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.
    All Cause Mortality
    Ramipril Candesartan Cilexetil Ramipril and Allopurinol Candesartan Cilexetil and Allopurinol
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Ramipril Candesartan Cilexetil Ramipril and Allopurinol Candesartan Cilexetil and Allopurinol
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/18 (22.2%) 6/18 (33.3%) 9/18 (50%) 5/18 (27.8%)
    Blood and lymphatic system disorders
    hospitalized for a critically high PT/INR 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    chronic anemia 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Cardiac disorders
    cardiac catheterization performed 1/17 (5.9%) 1 0/18 (0%) 0 1/18 (5.6%) 1 1/18 (5.6%) 1
    coronary artery bypass grafting 1/17 (5.9%) 1 2/18 (11.1%) 2 0/18 (0%) 0 1/18 (5.6%) 1
    hospitalized for chest pain; no surgical intervention 1/17 (5.9%) 1 2/18 (11.1%) 2 0/18 (0%) 0 0/18 (0%) 0
    hospitalized for prophylactic ICD implantation 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    death due to cardiac arrest 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    aortic valve replacement 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    coronary artery stent 0/18 (0%) 0 3/18 (16.7%) 3 0/18 (0%) 0 0/18 (0%) 0
    adenosine MIBI GXT positive for ischemic heart disease 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0
    coronary angioplasty 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0
    Gastrointestinal disorders
    adenocarcinoma of the pancreas 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    General disorders
    hospitalized due to chest pain; depressed TSH of 0.009 and hematocrit of 22 with a negative hemocult 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    hospitalized --paroxysmal atrial fibrillation, acute gouty arthritis, chronic renal failure 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    hospitalized for pneumonia and acute exudative tonsillitis 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    hospitalized for fever, cough, and general malaise; Hemodialysis was performed twice 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    infection resulting to altered mental status; episode of major depression; renal failure 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    death due to heart failure and renal failure 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    enterococcus endocarditis; ischemic right leg and GI bleed. 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0
    Infections and infestations
    elevated WBC; Chest x-ray revealed pleural thickening; cultures revealed klebsiella oxytoca 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    Musculoskeletal and connective tissue disorders
    hospitalized for anterior cervical discectomy of C5-C6 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Nervous system disorders
    acute anterior left middle cerebral artery distribution infarction 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    episode of slurred speech and memory loss at home 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0
    Renal and urinary disorders
    hospitalized for hematuria brought on by cystoscopy and right ureteroscopy 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    hospitalized for acute pyelonephritis 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    acute renal failure 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0
    Vascular disorders
    left above-knee amputation related to occlusion of his left external iliac artery 1/17 (5.9%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0
    hospitalized for elective abdominal aortogram 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Other (Not Including Serious) Adverse Events
    Ramipril Candesartan Cilexetil Ramipril and Allopurinol Candesartan Cilexetil and Allopurinol
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/18 (16.7%) 4/18 (22.2%) 6/18 (33.3%) 3/18 (16.7%)
    Cardiac disorders
    increased shortness of breath 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    CHEST WALL PAIN 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    SEVERE AORTIC REGURGITATION 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Eye disorders
    CATARACT REPAIR LEFT EYE 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Gastrointestinal disorders
    abdominal cramping 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    General disorders
    INTOLERANCE TO ACE-I 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0
    Musculoskeletal and connective tissue disorders
    WORSENING RIGHT HIP 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0
    worsening lower back pain 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0
    STERNOTOMY MUSCULOSKELETAL PAIN 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0
    BILATERAL HIP ARTHRITIS 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    LOWER PAIN 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Renal and urinary disorders
    ACUTE RENAL INSUFFICIENCY 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1
    GOUT 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0
    HYPERKALEMIA 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0
    placement of AV fistula 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    ACUTE BRONCHITIS 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Louis . J. Dell'Italia, M.D
    Organization University of Alabama at Birmingham
    Phone 205-934-3969
    Email Dell'Italia@PHYSIOLOGY.UAB.EDU
    Responsible Party:
    Dr. Louis J. Dell'Italia, Principal Investigator, University of Alabama at Birmingham
    ClinicalTrials.gov Identifier:
    NCT01052272
    Other Study ID Numbers:
    • F040105007
    First Posted:
    Jan 20, 2010
    Last Update Posted:
    Dec 17, 2012
    Last Verified:
    Nov 1, 2012