Clinical trial NCT01542502: Pilot Feasibility Study of the Safety and Efficacy of Anakinra in Heart Failure With Preserved Ejection Fraction
Official title: Pilot Feasibility Study of the Safety and Efficacy of Anakinra in Heart Failure With Preserved Ejection Fraction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure
Keywords: Heart failure with preserved ejection fraction
Diastolic heart failure
Aerobic exercise performance
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: American Heart Association
First posted: 2012-03-02
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This will be a randomized, double-blind, crossover pilot study to measure the safety and feasibility of Interleukin-1 (IL-1) blockade with Anakinra in patients with stable heart failure with preserved ejection fraction.


Eligibility criteria: Inclusion Criteria:

* Symptoms and signs of congestive heart failure
* Recent Imaging Study (\<12 months) showing Left Ventricular Ejection Fraction (LVEF) \>50% and Left Ventricular End Diastolic Volume Index (LVEDVI) \<97ml/m2
* Evidence of abnormal Left Ventricular (LV) relaxation, filling, diastolic distensibility, and diastolic stiffness as shown by one of the following:

  1. Invasive Hemodynamic measurements

     * mean Pulmonary Capillary Wedge pressure (mPCW) \>12
     * Left Ventricular End Diastolic Pressure (LVEDP) \>16 mmHg
  2. Tissue Doppler Echocardiogram

     * E/E' \>15
     * E/E' 8-15 and one of the following

       * Left Ventricular Hypertrophy (LVH)
       * Atrial Fibrillation
       * Left Atrial Enlargement
       * E/A \<0.5 + Deceleration Time (DT) \>280 (if \>50yrs of age)
  3. Biomarkers
* Brain Natriuretic Peptide (BNP) \>200pg/mL

Exclusion Criteria:

* Age \<18
* Recent changes (previous 3 months) in HF maintenance medications (beta-blockers, angiotensin converting enzyme \[ACE\] inhibitors, aldosterone antagonists, vasodilators, cardiac glycosides, diuretics)
* Hospitalization for worsening Heart Failure (HF) or acute decompensated HF within the previous 12months
* Anticipated need for cardiac resynchronization therapy (CRT) or automated-implantable cardioverter defibrillator (AICD)
* Angina or electrocardiograph (ECG) changes that limit maximum exertion during cardiopulmonary exercise testing
* Active infection including chronic infection
* Active cancer
* Recent (\<14 days) use of anti-inflammatory drugs (not including Non-Steroidal Anti-Inflammatory Drugs \[NSAIDs\]), Chronic inflammatory disorder (including but not limited to rheumatoid arthritis, systemic lupus erythematosus), malignancy, or any comorbidity limiting survival or ability to complete the study
* Pregnancy (determined by urine pregnancy test in women of childbearing potential)
* Inability to give informed consent
* Other conditions limiting completion of cardiopulmonary exercise test or completion of the study

Primary outcomes:
measure: Peak Oxygen Consumption (Peak VO2)
timeFrame: 14 days
Secondary outcomes:
measure: Exercise Time
timeFrame: 14 days
Other outcomes:
measure: Correlation Between Endpoints
timeFrame: 28 days
measure: Heart Failure Symptoms (DASI)
timeFrame: 28 days
measure: Adverse Events
timeFrame: 28 days
measure: Inflammatory Biomarkers
timeFrame: 28 days
measure: Ventilatory Efficiency (VE/VCO2 [Carbon Dioxide] Slope)
timeFrame: 14 days
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Antonio Abbate, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: