Interleukin-1 Blockade in HF With Preserved EF (D-HART2)
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|ClinicalTrials.gov Identifier: NCT02173548|
Recruitment Status : Completed
First Posted : June 25, 2014
Results First Posted : June 19, 2018
Last Update Posted : June 19, 2018
- Heart Failure with Preserved Ejection Fraction (HFpEF) is a common form of heart failure
- Standard treatment for heart failure, show less than ideal results in HFpEF
- Evidence of systemic inflammation is common in all forms of heart failure, including HFpEF
- The main hypothesis of this study is that systemic inflammation contributes to heart failure symptoms and exercise limitations in patients with HFpEF
- The main objective is to treat patients with HFpEF and evidence of systemic inflammation with an anti-inflammatory drug targeting Interleukin-1 (or placebo) to determine effects on cardiovascular function
|Condition or disease||Intervention/treatment||Phase|
|Heart Failure With Normal Ejection Fraction||Drug: Anakinra Drug: Placebo||Phase 2|
Heart Failure with Preserved Ejection Fraction (HFpEF) is a common form of heart failure, characterized by symptoms of congestion and impaired exercise tolerance, secondary to impaired left ventricular filling (diastole) in absence of a significant impairment in contractility (LVEF>50%) or significant valvular abnormalities, shunts or intra- or extra-cavitary obstruction.
The standard treatment for patient with heart failure is very effective in Heart Failure with Reduced Ejection Fraction (HFrEF), but it not very effective in HFpEF.
Evidence of systemic inflammation is common in all forms of heart failure, including HFpEF, and predicts worse outcomes. C reactive protein (CRP) is the preferred inflammatory biomarker used as risk predictor for cardiovascular disease. Patients with heart failure (HFpEF or HFrEF) with elevated CRP levels are more likely to be severely limited by heart failure symptoms, are more likely to be admitted to the hospital for heart failure, and are more likely to die of cardiac causes.
Preclinical studies show that a key mediator of systemic inflammation, Interleukin-1 (IL-1), impairs cardiac and vascular function, and may contribute to the pathogenesis of heart failure.
The main hypothesis of this study is that systemic inflammation, and IL-1 in particular, contributes to heart failure symptoms and exercise limitations in patients with HFpEF.
The main objective is to treat patients with HFpEF and evidence of systemic inflammation with an IL-1 blocker, anakinra (recombinant human IL-1 receptor antagonist)(or placebo) to determine effects on exercise capacity measured as peak oxygen consumption at maximal cardiopulmonary exercise testing.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||31 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Interleukin-1 Blockade in Heart Failure With Preserved Ejection Fraction (HFpEF): a Randomized Placebo-controlled Double Blinded Study (D-HART2)|
|Study Start Date :||September 2014|
|Actual Primary Completion Date :||April 11, 2017|
|Actual Study Completion Date :||June 1, 2017|
Active Comparator: Anakinra
Anakinra 100 mg given subcutaneously once daily for 12 weeks
Other Name: Kineret
Placebo Comparator: Placebo
- Change in Aerobic Exercise Capacity [ Time Frame: Baseline to 12 weeks ]Absolute changes in aerobic exercise capacity (peak VO2) after 12 weeks treatment. This will compare patients treated with anakinra and provide a randomized, double-blinded assessment of the effects of IL-1β blockade on aerobic exercise performance.
- Change in Ventilatory Eefficiency [ Time Frame: Baseline to 12 weeks ]Absolute changes in ventilatory efficiency (VE/VCO2 [carbon dioxide] slope) after 12 weeks treatment. This will compare patients treated with anakinra vs placebo, and provide a randomized, double-blinded assessment of the effects of IL-1β blockade on aerobic exercise performance.
- Echocardiographic Assessment of Diastolic and Systolic Function (Left Ventricular Ejection Fraction) [ Time Frame: 12 weeks ]Structural and functional echocardiographic parameters include left and right ventricular dimensions, mass, systolic and diastolic function. (Change in e')
- Change in Diastolic and Contractile Reserve (e' Velocity and E/e' Ratio) [ Time Frame: Baseline to 12 weeks ]Exercise stress echocardiography will be performed at baseline and 12 weeks to measure diastolic and contractile reserve. We will perform an assessment before initiation of exercise and immediately after cessation of peak exercise.
- Change in Inflammation (C Reactive Protein Levels) [ Time Frame: Baseline to 12 weeks ]The change C reactive protein (CRP) levels will be reported at 12 weeks. Higher C reactive protein levels indicate greater inflammation.
- Change in Quality of Life Questionnaire-Minnesota Living With Heart Failure Questionnaire (MLWHF) [ Time Frame: Baseline to 24 weeks ]The Minnesota Living with Heart Failure questionnaire (MLWHF) is a 21-question graded questionnaire that has been extensively used to measure impairment in quality of life in patients with HF, with higher scores reflecting increased burden of HF symptoms. The questionnaire will be administered in accordance with cardiopulmonary test (CPET) and echocardiography. Scores range from zero to 105 with lower scores indicating better quality of life.
- Change in Quality of Life Questionnaire-Duke Activity Status Index (DASI) [ Time Frame: Baseline to 12 weeks ]Two independent questionnaires will be used to assess quality of life and HF symptoms. The Duke Activity Status Index (DASI) questionnaire is a 12-question, yes/no, instrument that allows for the calculation of perceived functional capacity, in which each question describes a different physical activity and the questions are weighted according to their degree of physical exertion. Higher scores indicate greater functional capacity. The questionnaire will be administered at 0, 4, 12 and 24 weeks in accordance with cardiopulmonary test (CPET) and echocardiography. Scores range from zero to 58.2 with higher scores indicating higher functional status.
- Hospital Admission for Acute Decompensated Heart Failure [ Time Frame: 24 weeks ]Number of participants admitted to hospital for acute decompensated heart failure
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02173548
|United States, Virginia|
|Virginia Commonwealth University|
|Richmond, Virginia, United States, 23298|
|Principal Investigator:||Antonio Abbate, MD, PhD||Virginia Commonwealth University|
|Principal Investigator:||Benjamin Van Tassell, PharmD||Virginia Commonwealth University|