Pilot Feasibility Study of the Safety and Efficacy of Anakinra in Heart Failure With Preserved Ejection Fraction

This study has been completed.
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT01542502
First received: February 23, 2012
Last updated: August 30, 2013
Last verified: August 2013
  Purpose

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


Condition Intervention
Heart Failure
Drug: Anakinra
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pilot Feasibility Study of the Safety and Efficacy of Anakinra in Heart Failure With Preserved Ejection Fraction

Resource links provided by NLM:


Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • Peak oxygen consumption (peak VO2) [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
    The primary endpoint is the change in peak oxygen consumption among stable heart failure patients (n = 14) following 14-days treatment with daily doses of Anakinra 100 mg (SC, subcutaneous).


Secondary Outcome Measures:
  • Aerobic exercise parameters (VCO2, VE/VCO2 slope, exercise time) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Secondary endpoints will include interval change from baseline in other exercise parameters (peak VO2, exercise time, ventilatory efficiency) upon completion of 2 weeks treatment and throughout 4-week duration of study

  • Inflammatory biomarkers [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Secondary endpoints will include interval change from baseline in inflammatory biomarkers (high-sensitivity C-reactive protein, whole blood assay) upon completion of 2 weeks treatment and throughout 4-week duration of study.

  • Heart failure symptoms (DASI) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Secondary endpoints will include interval change from baseline in HF symptoms as measured by Duke Activity Status Index (DASI) upon completion of 2 weeks treatment and throughout the 4-week duration of study.

  • Adverse events [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Secondary endpoints will include assessment of adverse events and hospitalizations during 4-week duration of study.

  • Correlation between endpoints [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Secondary endpoints will include correlation studies between interval changes in biomarkers, exercise parameters, failure symptoms, adverse events and hospitalizations during 4-week duration of study.


Enrollment: 11
Study Start Date: February 2012
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anakinra
Treatment with daily subcutaneous injections of Anakinra 100 mg
Drug: Anakinra
Anakinra 100 mg daily subcutaneous injection
Other Names:
  • Recombinant human Interleukin-1 receptor antagonist
  • Kineret
Placebo Comparator: Placebo
Treatment with daily subcutaneous injection of placebo
Drug: Placebo
Placebo daily subcutaneous injection

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Symptoms and signs of congestive heart failure
  • Recent Imaging Study (<12 months) showing LVEF>50% and LVEDVI<97ml/m2
  • Evidence of abnormal LV relaxation, filling, diastolic distensibility, and diastolic stiffness as shown by one of the following:

    1. Invasive Hemodynamic measurements

      • mPCW >12
      • LVEDP>16mmHg
    2. Tissue Doppler Echocardiogram

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

        • LVH
        • Afib
        • LAE
        • E/A<0.5+DT>280(if >50yrs of age)
    3. Biomarkers
  • 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 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 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01542502

Locations
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Virginia Commonwealth University
American Heart Association
Investigators
Principal Investigator: Antonio Abbate, MD, PhD Virginia Commonwealth University
  More Information

No publications provided

Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT01542502     History of Changes
Other Study ID Numbers: HM14079
Study First Received: February 23, 2012
Last Updated: August 30, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Virginia Commonwealth University:
Heart failure with preserved ejection fraction
Diastolic heart failure
Aerobic exercise performance

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 23, 2014