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

Primary Purpose

Heart Failure

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Anakinra
Placebo
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 with preserved ejection fraction, Diastolic heart failure, Aerobic exercise performance

Eligibility Criteria

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

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

Sites / Locations

  • Virginia Commonwealth University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Anakinra

Placebo

Arm Description

Treatment with daily subcutaneous injections of Anakinra 100 mg

Treatment with daily subcutaneous injection of placebo

Outcomes

Primary Outcome Measures

Peak Oxygen Consumption (Peak VO2)
The primary endpoint is the change in peak oxygen consumption among stable heart failure patients (n = 12) following 14-days treatment with daily doses of Anakinra 100 mg (SC, subcutaneous).

Secondary Outcome Measures

Exercise Time
Interval change from baseline in duration of exercise during a standardized cardiopulmonary exercise test upon completion of 2 weeks treatment

Full Information

First Posted
February 23, 2012
Last Updated
December 12, 2016
Sponsor
Virginia Commonwealth University
Collaborators
American Heart Association
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1. Study Identification

Unique Protocol Identification Number
NCT01542502
Brief Title
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

2. Study Status

Record Verification Date
December 2016
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Virginia Commonwealth University
Collaborators
American Heart Association

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
Heart failure with preserved ejection fraction, Diastolic heart failure, Aerobic exercise performance

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Anakinra
Arm Type
Experimental
Arm Description
Treatment with daily subcutaneous injections of Anakinra 100 mg
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Treatment with daily subcutaneous injection of placebo
Intervention Type
Drug
Intervention Name(s)
Anakinra
Other Intervention Name(s)
Recombinant human Interleukin-1 receptor antagonist, Kineret
Intervention Description
Anakinra 100 mg daily subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sodium Chloride (NaCl) 0.9%
Intervention Description
Placebo daily subcutaneous injection
Primary Outcome Measure Information:
Title
Peak Oxygen Consumption (Peak VO2)
Description
The primary endpoint is the change in peak oxygen consumption among stable heart failure patients (n = 12) following 14-days treatment with daily doses of Anakinra 100 mg (SC, subcutaneous).
Time Frame
14 days
Secondary Outcome Measure Information:
Title
Exercise Time
Description
Interval change from baseline in duration of exercise during a standardized cardiopulmonary exercise test upon completion of 2 weeks treatment
Time Frame
14 days
Other Pre-specified Outcome Measures:
Title
Correlation Between Endpoints
Description
Correlation between interval change in peak VO2 and high sensitivity C-reactive protein
Time Frame
28 days
Title
Heart Failure Symptoms (DASI)
Description
Interval change from baseline in Heart Failure (HF) symptoms as measured by Duke Activity Status Index (DASI) upon completion of 2 weeks treatment.
Time Frame
28 days
Title
Adverse Events
Description
Additional endpoints will include assessment of adverse events and hospitalizations during 4-week duration of study.
Time Frame
28 days
Title
Inflammatory Biomarkers
Description
Interval change from baseline in high-sensitivity C-reactive protein upon completion of 2 weeks treatment.
Time Frame
28 days
Title
Ventilatory Efficiency (VE/VCO2 [Carbon Dioxide] Slope)
Description
Interval change from baseline in ventilatory efficiency (VE/VCO2 slope) upon completion of 2 weeks treatment.
Time Frame
14 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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: Invasive Hemodynamic measurements mean Pulmonary Capillary Wedge pressure (mPCW) >12 Left Ventricular End Diastolic Pressure (LVEDP) >16 mmHg 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) 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonio Abbate, MD, PhD
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

Learn more about this trial

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

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