Clinical trial NCT01300650: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Heart Failure
Keywords: Heart failure
Inflammation
Interleukin-1
Cardiopulmonary exercise
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Center for Research Resources (NCRR)
First posted: 2011-02-21
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Median Interval Change From Baseline in Peak VO2
timeFrame: 14 days
measure: Median Interval Change From Baseline in the Minute Ventilation and Carbon Dioxide Production (VE/VCO2 Slope)
timeFrame: 14 days
Secondary outcomes:
measure: Interval Change From Baseline in Heart Failure Symptoms as Measured by Duke Activity Status Index (DASI)
timeFrame: 14 days
Other outcomes:
measure: Interval Change From Baseline in Biomarkers (High-sensitivity C-reactive Protein, Whole Blood Assay, Brain Natriuretic Peptide)
timeFrame: 14 days
measure: Correlation Between Interval Changes in Biomarkers, Peak VO2, and VE/VCO2
timeFrame: 14 days
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Benjamin W Van Tassell, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
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.