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

NCT01300650 | Completed Phase 1 Results

• 2 other identifiers: AIR-HF Pilot Study1KL2RR031989-01
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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).

Conditions

Heart Failure

Keywords

Heart failure; Inflammation; Interleukin-1; Cardiopulmonary exercise

Outcome Measures

Primary Outcomes (2)

• 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 \[baseline\])

  14 days

• 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 \[baseline\])

  14 days

Secondary Outcomes (1)

• Interval Change From Baseline in Heart Failure Symptoms as Measured by Duke Activity Status Index (DASI)

  14 days

Other Outcomes (2)

• Interval Change From Baseline in Biomarkers (High-sensitivity C-reactive Protein, Whole Blood Assay, Brain Natriuretic Peptide)

  14 days

• Correlation Between Interval Changes in Biomarkers, Peak VO2, and VE/VCO2

  14 days

Study Arms (1)

Anakinra

EXPERIMENTAL

Drug: Anakinra

Interventions

Anakinra DRUG

Anakinra 100 mg subcutaneous injection daily

Anakinra

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Institutes of Health (NIH): collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Related Publications (1)

• 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.

  PMID: 22438931 DERIVED

MeSH Terms

Conditions

Heart Failure; Inflammation

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Benjamin Van Tassell
• Organization: Virginia Commonwealth University

bvantassell@vcu.edu

8049820997

Study Officials

• Benjamin W Van Tassell, PharmD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2011
• First Posted: February 21, 2011
• Study Start: February 1, 2011
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: November 30, 2017
• Results First Posted: May 16, 2013

Record last verified: 2017-10

Locations

US (1)