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

December 12, 2016 updated by: Virginia Commonwealth University
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Anakinra
Treatment with daily subcutaneous injections of Anakinra 100 mg
Drug: Anakinra
Anakinra 100 mg daily subcutaneous injection
Other Names:
  • Kineret
  • Recombinant human Interleukin-1 receptor antagonist
Placebo Comparator: Placebo
Treatment with daily subcutaneous injection of placebo
Drug: Placebo
Placebo daily subcutaneous injection
Other Names:
  • Sodium Chloride (NaCl) 0.9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peak Oxygen Consumption (Peak VO2)
Time Frame: 14 days
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).
14 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exercise Time
Time Frame: 14 days
Interval change from baseline in duration of exercise during a standardized cardiopulmonary exercise test upon completion of 2 weeks treatment
14 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation Between Endpoints
Time Frame: 28 days
Correlation between interval change in peak VO2 and high sensitivity C-reactive protein
28 days
Heart Failure Symptoms (DASI)
Time Frame: 28 days
Interval change from baseline in Heart Failure (HF) symptoms as measured by Duke Activity Status Index (DASI) upon completion of 2 weeks treatment.
28 days
Adverse Events
Time Frame: 28 days
Additional endpoints will include assessment of adverse events and hospitalizations during 4-week duration of study.
28 days
Inflammatory Biomarkers
Time Frame: 28 days
Interval change from baseline in high-sensitivity C-reactive protein upon completion of 2 weeks treatment.
28 days
Ventilatory Efficiency (VE/VCO2 [Carbon Dioxide] Slope)
Time Frame: 14 days
Interval change from baseline in ventilatory efficiency (VE/VCO2 slope) upon completion of 2 weeks treatment.
14 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Virginia Commonwealth University

Collaborators

American Heart Association

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2012

Primary Completion (Actual)

June 1, 2013

Study Completion (Actual)

June 1, 2013

Study Registration Dates

First Submitted

February 23, 2012

First Submitted That Met QC Criteria

March 1, 2012

First Posted (Estimate)

March 2, 2012

Study Record Updates

Last Update Posted (Estimate)

February 6, 2017

Last Update Submitted That Met QC Criteria

December 12, 2016

Last Verified

December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HM14079

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe