Effects of Aliskiren on Patient With Heart Failure and a Normal Ejection Fraction

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT00982033
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 52
• Location: 1
• Arms: 2
• Duration (Months): 29
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

The primary objective of this study is to determine whether treatment with aliskiren (300 mg) compared to placebo will improve treadmill exercise time in older (age ≥ 55 years) patients with heart failure and normal ejection fraction (HFNEF).

Condition or Disease	Intervention/Treatment	Phase
Heart Failure	Drug: aliskiren; Drug: placebo	Phase 4

Detailed Description

Heart Failure with Normal Ejection Fraction (HFNEF) is the most common form of heart failure, particularly in older persons. However, the optimal therapy for this disorder has not been defined. The primary chronic symptom in HFNEF is exercise intolerance, manifested by shortness of breath and fatigue with exercise. This is the major determinant of quality of life, can be measured objectively and reproducibly and is modifiable.

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Blinded, Placebo-Controlled Six Month Treatment Trial of Aliskiren to Improve Exercise Tolerance in Older Patients With Heart Failure and Normal Ejection Fraction
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Aliskiren 50 % of subjects participating in this trial will be on the active medication, Aliskiren 300mg qd, the other 50% will be on placebo.	Drug: aliskiren; aliskiren 300mg qd versus placebo for 24 weeks.; Other Names: Tekturna
Placebo Comparator: Placebo 50% of subjects will be randomized to placebo.	Drug: placebo; placebo qd for 24 weeks

Outcome Measures

Primary Outcome Measures

1. Exercise Treadmill Time [Baseline, 24 week visit]

   Treadmill exercise time to exhaustion on the modified naughton protocol. LS-mean is in effect, within-group means appropriately adjusted for the other effects in the model.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female ≥ 55 years of age

• Symptomatic HFNEF of at least 1 month duration.

• Reduced early diastolic mitral annular velocity by tissue Doppler

• Left ventricular ejection fraction (LVEF ≥ 0.50)

• Baseline exercise intolerance

• Patients who are able to provide written informed consent

• Stable medical therapy for 30 days prior to screening

Exclusion Criteria:

• Seated blood pressure ≥ 160/90 mmHg at Visit 1 (screening)

• Clinically significant pulmonary disease

• Known history of documented EF < 0.45 at any time

• Clinically unstable heart failure, medication changes for worsening heart failure symptoms within the past 4 weeks

• Severe anemia (Hgb <10 mg/dL)

• Clinical evidence of uncontrolled hypo or hyperthyroidism

• Clinically significant valvular heart disease

• Surgical correction of valvular heart disease within the last year

• Known familial hypertrophic cardiomyopathy or hypertrophic obstructive cardiomyopathy

• Known restrictive cardiomyopathy or systemic illness known to be associated with infiltrative myocardial disease (e.g. amyloidosis, sarcoidosis, hemachromatosis)

• Pericardial restriction or hemodynamically significant pericardial effusion

• Cor pulmonal or other causes of right heart failure not related to LV dysfunction

• Extreme obesity (weight > 325 pounds)

• Acute coronary syndrome within past 3 months

• Coronary artery revascularization within past 3 months

• Peripheral artery revascularization within past 3 months

• Acute cerebrovascular syndrome (stroke or TIA) within the past 3 months

• Uncontrolled symptomatic brady- or tachyarrhythmia

• Creatinine > 2.5 mg/dl at screening

• Potassium > 5.2 meq/l at screening

• Prior treatment with, hypersensitivity to, intolerance of or contra-indication to aliskiren

• Current treatment with antidepressant medication in the MAO(Monoamine Oxidase) inhibitor or SSRI(Selective serotonin reuptake inhibitors) class

• Current participation in another clinical trial

• Current treatment with both an ACE(Angiotensin-converting enzyme) inhibitor and an angiotensin receptor antagonist.

• Known significant bilateral renal artery stenosis

• Serious non-cardiovascular disease severely limiting life expectancy

• Previous major organ (e.g., lung, liver, heart, kidney) transplantation or on a transplant waiting list

• Any condition that is likely to prevent the patient from complying with the requirements of the study or completing the study (e.g., history of poor compliance, alcohol or drug dependency, psychiatric illness, no permanent home)

• Pregnant women, nursing women, and women of childbearing potential.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157

Sponsors and Collaborators

• Wake Forest University Health Sciences
• Novartis Pharmaceuticals

Investigators

• Principal Investigator: Dalane W Kitzman, MD, Wake Forest University Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT00982033
• Other Study ID Numbers: IRB00008625; CTA study # CSPP100AUS13T; GTS # 34136
• First Posted: Sep 22, 2009
• Last Update Posted: Feb 27, 2019
• Last Verified: Feb 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Wake Forest University Health Sciences: Heart failure with normal ejection fraction; Elderly
• Additional relevant MeSH terms: Heart Failure

Study Results

Participant Flow

Arm/Group Title	Aliskiren	Placebo
Arm/Group Description	50 % of subjects participating in this trial will be on the active medication, Aliskiren 300mg qd, the other 50% will be on placebo. aliskiren: aliskiren 300mg qd versus placebo for 24 weeks.	50% of subjects will be randomized to placebo. placebo: placebo qd for 24 weeks
Period Title: Overall Study
STARTED	25	27
COMPLETED	25	27
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Aliskiren	Placebo	Total
Arm/Group Description	50 % of subjects participating in this trial will be on the active medication, Aliskiren 300mg qd. aliskiren: aliskiren 300mg qd for 24 weeks.	50% of subjects participating in this trial will be randomized to placebo. placebo: placebo qd for 24 weeks.	Total of all reporting groups
Overall Participants	25	27	52
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.3 (6.3)	70.6 (7.7)	69.9 (7.04)
Sex: Female, Male (Count of Participants)
Female	19 76%	23 85.2%	42 80.8%
Male	6 24%	4 14.8%	10 19.2%

Outcome Measures

1. Primary Outcome

Title	Exercise Treadmill Time
Description	Treadmill exercise time to exhaustion on the modified naughton protocol. LS-mean is in effect, within-group means appropriately adjusted for the other effects in the model.
Time Frame	Baseline, 24 week visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aliskiren	Placebo
Arm/Group Description	50 % of subjects participating in this trial will be on the active medication, Aliskiren 300mg qd. aliskiren: aliskiren 300mg qd for 24 weeks.	50% of subjects participating in this trial will be randomized to placebo. placebo: placebo qd for 24 weeks.
Measure Participants	25	27
Baseline	621 (120)	580 (126)
24 Week	624 (151)	579 (145)
LS Mean	607 (13)	605 (12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aliskiren, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.90
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Time Frame	2 years, 2 months
Arm/Group Title	Aliskiren		Placebo
Arm/Group Description	50 % of subjects participating in this trial will be on the active medication, Aliskiren 300mg qd. aliskiren: aliskiren 300mg qd for 24 weeks.		50% of subjects participating in this trial will be randomized to placebo. placebo: placebo qd for 24 weeks.
All Cause Mortality
	Aliskiren		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Aliskiren		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		4/27 (14.8%)
Cardiac disorders
dyspnea, CHF exacerbation	0/25 (0%)	0	2/27 (7.4%)	2
Gastrointestinal disorders
small bowel obstruction	0/25 (0%)	0	2/27 (7.4%)	2
Other (Not Including Serious) Adverse Events
	Aliskiren		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/25 (24%)		13/27 (48.1%)
Cardiac disorders
increased blood pressure	0/25 (0%)	0	1/27 (3.7%)	1
atrial fibrillation and or palpitations	1/25 (4%)	1	1/27 (3.7%)	1
Ear and labyrinth disorders
ear and or eye infection	1/25 (4%)	1	1/27 (3.7%)	1
Endocrine disorders
viral symdrom and or possible thrush	1/25 (4%)	1	0/27 (0%)	0
Gastrointestinal disorders
abdominal pain, colitis, and or virus	1/25 (4%)	1	2/27 (7.4%)	2
Musculoskeletal and connective tissue disorders
leg, back and or joint pain	2/25 (8%)	2	2/27 (7.4%)	2
Nervous system disorders
altered mental status	0/25 (0%)	0	2/27 (7.4%)	2
numbness in left arm	0/25 (0%)	0	1/27 (3.7%)	1
Respiratory, thoracic and mediastinal disorders
pneumonia and or upper respiratory infection	0/25 (0%)	0	2/27 (7.4%)	2
Surgical and medical procedures
root canal	0/25 (0%)	0	1/27 (3.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.