Aliskiren and Renin Inhibition in Diastolic Heart Failure - Full Text View

Sponsor:	Texas Tech University Health Sciences Center
Information provided by:	Texas Tech University Health Sciences Center
ClinicalTrials.gov Identifier:	NCT00773084

Purpose

This study is being conducted to compare the effects that 2 different combinations of heart failure medications have on the levels of certain blood markers which cause and/or worsen heart failure. Additionally, the investigators will investigate any differences that may exist between Hispanics and Non-Hispanics. The investigators hope to find that Hispanic Americans will have a greater response to this new regimen compared to non-Hispanic Americans.

Condition	Intervention
Diastolic Heart Failure	Drug: Aliskiren plus spironolactone vs. Lisinopril plus spironolactone

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Aliskiren and Renin Inhibition in Diastolic Heart Failure in Mexican Americans

Resource links provided by NLM:

MedlinePlus related topics: Heart Failure

Drug Information available for: Spironolactone Lisinopril Aliskiren

U.S. FDA Resources

Further study details as provided by Texas Tech University Health Sciences Center:

Primary Outcome Measures:

Compare the baseline level of RAAS dysregulation between Mexican Americans and non-Hispanic whites with stable diastolic HF by measuring established biomarkers. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Evaluate the superiority of aliskiren plus spironolactone combination over an lisinopril plus spironolactone combination in inhibiting the RAAS system among patients with diastolic HF. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Compare the clinical and biological benefit of RAAS system inhibition between aliskiren plus spironolactone and lisinopril plus spironolactone as measured by clinical indicators and serum biomarkers [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Assess ethnicity-specific differences in the clinical response to either RAAS inhibition treatment between Mexican Americans and non-Hispanic whites. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	September 2008
Estimated Study Completion Date:	August 2009
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
No Intervention: Nationality Hispanic versus Non-Hispanic (white) Americans	Drug: Aliskiren plus spironolactone vs. Lisinopril plus spironolactone Subjects will be in the study for a total of 8 weeks. Subjects with stable diastolic HF on current ACEI therapy will be randomized into two treatment groups. The study group will receive Aliskiren plus spironolactone and the control group will receive Lisinopril plus spironolactone. These 2 groups will be further divided according to ethnicity: Mexican Americans and non-Hispanic whites. Sixty patients will be recruited, 30 per treatment group. Subjects will have a 2 week wash-out period. At the end of this period, blood will be collected and subjects will be asked to take the assigned medication once daily for 6 weeks. Subjects will be asked to return every 2 weeks at which time blood pressure, serum potassium and creatinine levels will be assessed. Their medications will be titrated depending on clinical tolerance and symptom control. At the end of 6 weeks of treatment blood markers will be drawn and differences will be analyzed. Other Names: Tekturna Lisinopril Spironolactone
Active Comparator: Drug Aliskiren plus spironolactone vs. Lisinopril plus spironolactone	Drug: Aliskiren plus spironolactone vs. Lisinopril plus spironolactone Subjects will be in the study for a total of 8 weeks. Subjects with stable diastolic HF on current ACEI therapy will be randomized into two treatment groups. The study group will receive Aliskiren plus spironolactone and the control group will receive Lisinopril plus spironolactone. These 2 groups will be further divided according to ethnicity: Mexican Americans and non-Hispanic whites. Sixty patients will be recruited, 30 per treatment group. Subjects will have a 2 week wash-out period. At the end of this period, blood will be collected and subjects will be asked to take the assigned medication once daily for 6 weeks. Subjects will be asked to return every 2 weeks at which time blood pressure, serum potassium and creatinine levels will be assessed. Their medications will be titrated depending on clinical tolerance and symptom control. At the end of 6 weeks of treatment blood markers will be drawn and differences will be analyzed. Other Names: Tekturna Lisinopril Spironolactone

Arms

Assigned Interventions

No Intervention: Nationality

Hispanic versus Non-Hispanic (white) Americans

Drug: Aliskiren plus spironolactone vs. Lisinopril plus spironolactone

Subjects will be in the study for a total of 8 weeks. Subjects with stable diastolic HF on current ACEI therapy will be randomized into two treatment groups. The study group will receive Aliskiren plus spironolactone and the control group will receive Lisinopril plus spironolactone. These 2 groups will be further divided according to ethnicity: Mexican Americans and non-Hispanic whites. Sixty patients will be recruited, 30 per treatment group. Subjects will have a 2 week wash-out period. At the end of this period, blood will be collected and subjects will be asked to take the assigned medication once daily for 6 weeks. Subjects will be asked to return every 2 weeks at which time blood pressure, serum potassium and creatinine levels will be assessed. Their medications will be titrated depending on clinical tolerance and symptom control. At the end of 6 weeks of treatment blood markers will be drawn and differences will be analyzed.

Other Names:

Tekturna
Lisinopril
Spironolactone

Active Comparator: Drug

Aliskiren plus spironolactone vs. Lisinopril plus spironolactone

Drug: Aliskiren plus spironolactone vs. Lisinopril plus spironolactone

Subjects will be in the study for a total of 8 weeks. Subjects with stable diastolic HF on current ACEI therapy will be randomized into two treatment groups. The study group will receive Aliskiren plus spironolactone and the control group will receive Lisinopril plus spironolactone. These 2 groups will be further divided according to ethnicity: Mexican Americans and non-Hispanic whites. Sixty patients will be recruited, 30 per treatment group. Subjects will have a 2 week wash-out period. At the end of this period, blood will be collected and subjects will be asked to take the assigned medication once daily for 6 weeks. Subjects will be asked to return every 2 weeks at which time blood pressure, serum potassium and creatinine levels will be assessed. Their medications will be titrated depending on clinical tolerance and symptom control. At the end of 6 weeks of treatment blood markers will be drawn and differences will be analyzed.

Other Names:

Tekturna
Lisinopril
Spironolactone

Detailed Description:

Our main hypothesis is that in contrast to non Hispanic whites, the degree of RAAS system activation is more pronounced in Mexican Americans with diastolic HF and consequently their response to RAAS inhibition therapy is greater. Blocking the RAAS with renin inhibitor plus aldosterone receptor blocker should produce measurable changes in biomarkers as well as physiologic improvement that could therefore translate into improved clinical outcomes. These changes should be greater appreciated in Mexican Americans if the central pathophysiologic influence of HF in this population was RAAS maladaptation.

Eligibility

Ages Eligible for Study:	21 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Chronic stable diastolic HF documented by clinical diagnosis and echocardiogram within the last 2 years
NYHA classes I-III, symptomatically stable (for >1month)
Age 21-70 years
Either of Hispanic ethnicity (Mexican American origin) or non-Hispanic white
Patients on ACE inhibitor therapy (lisinopril)
Blood pressure >100/75 mmHg
Adequate birth control
Patients seen in TTUHSC Cardiology or Internal Medicine clinic for at least two visits since January 2008

Exclusion Criteria:

Acute coronary syndrome (within the last month).
Recent acute diastolic or systolic HF (within the last month)
Pancreatic disease
Renal artery stenosis
Pregnancy
History of angioedema
Severe hypotension (systolic BP<90mmHg or mean arterial pressure <65mmHg)
Hyperkalemia (defined by K+>5 mEq/L)
Chronic Kidney Disease (Stage 3 and above)
Systolic dysfunction (ejection fraction below 50%)
Ethnicity other than Mexican American or non-Hispanic white

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00773084

Locations

United States, Texas
Texas Tech University Health Sciences Center
Lubbock, Texas, United States, 79430

Sponsors and Collaborators

Texas Tech University Health Sciences Center

More Information

No publications provided

Responsible Party:	Selim Krim, MD, Texas Tech University Health Sciences Center--Dept. of Internal Medicine
ClinicalTrials.gov Identifier:	NCT00773084 History of Changes
Other Study ID Numbers:	ARID-HF
Study First Received:	October 15, 2008
Last Updated:	June 2, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by Texas Tech University Health Sciences Center:

Diastolic Heart Failure
Hispanic Americans
Aliskiren

Spironolactone
Lisinopril
Diastolic Heart Failure in Hispanic Americans

Additional relevant MeSH terms:

Heart Failure
Heart Failure, Diastolic
Heart Diseases
Cardiovascular Diseases
Spironolactone
Lisinopril
Aldosterone Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

Diuretics
Natriuretic Agents
Cardiovascular Agents
Therapeutic Uses
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Cardiotonic Agents
Protective Agents

ClinicalTrials.gov processed this record on February 09, 2012