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Pilot Study of the Safety and Efficacy of Anakinra (Recombinant Human Interleukin-1 Receptor Antagonist) in Heart Failure

This study has been completed.
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT01300650
First received: February 17, 2011
Last updated: April 2, 2013
Last verified: April 2013
History of Changes
  Purpose

This is an open-label, non-randomized, pilot-study to evaluate the effect of Interleukin-1 blockade on exercise capacity in patients with heart failure. Subjects will undergo cardiopulmonary exercise testing at baseline and after 2-weeks treatment with anakinra (recombinant human Interleukin-1 receptor antagonist).


Condition Intervention Phase
Heart Failure
 Drug: Anakinra
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of the Safety and Efficacy of Anakinra (Recombinant Human Interleukin-1 Receptor Antagonist) in Heart Failure

Resource links provided by NLM:

Drug Information available for: Anakinra
U.S. FDA Resources

Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • Median Interval Change From Baseline in Peak VO2 [ Time Frame: 14 days ] [ Designated as safety issue: No ]

    Peak VO2 is a measurement of oxygen consumption rate during exercise (milliliters of oxygen per minute). It is calculated by continuous measurement of oxygen consumed during exercise while patients breath through a mask/tube. To account for variability in patient size, the oxygen consumption is divided by patient body weight.

    The outcome measure time frame was 14 days. This means that change in peak VO2 was calculated as the difference between peak VO2 at baseline and 14 days. To calculate this change, we used the mathematical process of subtraction (change in peak VO2 = Peak VO2 [day 14] - Peak VO2 [baseline])


  • Median Interval Change From Baseline in the Minute Ventilation and Carbon Dioxide Production (VE/VCO2 Slope) [ Time Frame: 14 days ] [ Designated as safety issue: No ]

    The VE/VCO2 slope is calculated as the ratio of minute ventilation (VE) and carbon dioxide production (VCO2). Because these measurements share the same units, the resultant ratio is unitless.

    Change in VE/VCO2 slope was calculated as the change in VE/VCO2 slope between baseline and 14 days. We therefore calculated the difference between VE/VCO2 slope measurements that occurred at baseline and at 14 days (change in VE/VCO2 slope = VE/VCO2 slope [day 14] - VE/VCO2 slope [baseline])



Secondary Outcome Measures:
  • Interval Change From Baseline in Biomarkers (High-sensitivity C-reactive Protein, Whole Blood Assay, Brain Natriuretic Peptide) [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Interval Change From Baseline in Heart Failure Symptoms as Measured by Duke Activity Status Index (DASI) [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    The Duke Activity Status Index (DASI) is a scale that quantifies patients' ability to perform various tasks. The scale ranges from 0 (unable to perform any tasks) to 58.20 (able to perform all tasks). Higher scores reflect improved activity or improved heart failure symptoms. Lower scores reflect worsened ability or worsened heart failure symptoms.

  • Correlation Between Interval Changes in Biomarkers, Peak VO2, and VE/VCO2 [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Rate of Adverse Events and Hospitalizations [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]

Enrollment: 11
Study Start Date: February 2011
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anakinra Drug: Anakinra
Anakinra 100 mg subcutaneous injection daily

  Eligibility

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

Inclusion Criteria:

  • Confirmed diagnosis of heart failure
  • Recent echocardiogram documenting left ventricular ejection fraction <40%
  • High sensitivity C-reactive protein >2 mg/L.

Exclusion Criteria:

  • 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 12 months
  • 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 or baseline ECG changes that limit the ability to detect ischemia (i.e. left bundle-branch block).
  • 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, active infection, or any comorbidity limiting survival or ability to complete the study
  • Severe kidney dysfunction (eGFR <30 mL/min)
  • Coagulopathy (INR >1.5), thrombocytopenia (<50,000/mm3), or leukopenia (absolute neutrophil count <1,500/mm3)
  • Pregnancy (female patients will be required to take a urine pregnancy test)
  • Latex or rubber allergy
  • Inability to give informed consent
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01300650

Locations
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Virginia Commonwealth University
National Institutes of Health (NIH)
National Center for Research Resources (NCRR)
Investigators
Principal Investigator: Benjamin W Van Tassell, PharmD Virginia Commonwealth University
  More Information

No publications provided by Virginia Commonwealth University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT01300650     History of Changes
Other Study ID Numbers: AIR-HF Pilot Study, 1KL2RR031989-01
Study First Received: February 17, 2011
Results First Received: December 2, 2011
Last Updated: April 2, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Virginia Commonwealth University:
Heart failure
Inflammation
Interleukin-1
Cardiopulmonary exercise

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 June 18, 2013