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

Primary Purpose

Heart Failure

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Anakinra
Sponsored by
Virginia Commonwealth University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure focused on measuring Heart failure, Inflammation, Interleukin-1, Cardiopulmonary exercise

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Virginia Commonwealth University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Anakinra

Arm Description

Outcomes

Primary Outcome Measures

Median Interval Change From Baseline in Peak VO2
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)
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 Heart Failure Symptoms as Measured by Duke Activity Status Index (DASI)
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.

Full Information

First Posted
February 17, 2011
Last Updated
October 24, 2017
Sponsor
Virginia Commonwealth University
Collaborators
National Institutes of Health (NIH), National Center for Research Resources (NCRR)
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1. Study Identification

Unique Protocol Identification Number
NCT01300650
Brief Title
Pilot Study of the Safety and Efficacy of Anakinra (Recombinant Human Interleukin-1 Receptor Antagonist) in Heart Failure
Official Title
Pilot Study of the Safety and Efficacy of Anakinra (Recombinant Human Interleukin-1 Receptor Antagonist) in Heart Failure
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
August 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Virginia Commonwealth University
Collaborators
National Institutes of Health (NIH), National Center for Research Resources (NCRR)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
Heart failure, Inflammation, Interleukin-1, Cardiopulmonary exercise

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Anakinra
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Anakinra
Intervention Description
Anakinra 100 mg subcutaneous injection daily
Primary Outcome Measure Information:
Title
Median Interval Change From Baseline in Peak VO2
Description
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])
Time Frame
14 days
Title
Median Interval Change From Baseline in the Minute Ventilation and Carbon Dioxide Production (VE/VCO2 Slope)
Description
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])
Time Frame
14 days
Secondary Outcome Measure Information:
Title
Interval Change From Baseline in Heart Failure Symptoms as Measured by Duke Activity Status Index (DASI)
Description
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.
Time Frame
14 days
Other Pre-specified Outcome Measures:
Title
Interval Change From Baseline in Biomarkers (High-sensitivity C-reactive Protein, Whole Blood Assay, Brain Natriuretic Peptide)
Time Frame
14 days
Title
Correlation Between Interval Changes in Biomarkers, Peak VO2, and VE/VCO2
Time Frame
14 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benjamin W Van Tassell, PharmD
Organizational Affiliation
Virginia Commonwealth University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22438931
Citation
Van Tassell BW, Arena RA, Toldo S, Mezzaroma E, Azam T, Seropian IM, Shah K, Canada J, Voelkel NF, Dinarello CA, Abbate A. Enhanced interleukin-1 activity contributes to exercise intolerance in patients with systolic heart failure. PLoS One. 2012;7(3):e33438. doi: 10.1371/journal.pone.0033438. Epub 2012 Mar 16.
Results Reference
derived

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

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