Clinical trial NCT01479010: Pilot Study of the Safety and Efficacy of Anakinra (Recombinant Human Interleukin-1 Receptor Antagonist) in Pulmonary Hypertension
Official title: Pilot Study of the Safety and Efficacy of Anakinra (Recombinant Human Interleukin-1 Receptor Antagonist) in Pulmonary Hypertension
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Pulmonary Hypertension
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
First posted: 2011-11-24
Enrollment: 2
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 pulmonary hypertension. Subjects will undergo cardiopulmonary exercise testing at baseline, and after 4 weeks treatment with Anakinra (recombinant human Interleukin-1 receptor antagonist.


Eligibility criteria: Inclusion Criteria:

* Age \>18 years
* Diagnosis of PAH (from prior right heart catheterization), with functional class III symptoms of right ventricle failure despite optimal PAH therapy
* Mean pulmonary artery pressure \>25 mmHg
* Pulmonary capillary wedge pressure \<15 mmHg
* Pulmonary vascular resistance \>3 wood units

Exclusion Criteria:

* PAH due to connective tissue disease (including scleroderma), interstitial lung disease (total lung capacity \<65% predicted value), or cirrhosis (portopulmonary hypertension)
* 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)
* Thrombocytopenia (\<50,000/mm3), or neutropenia (absolute neutrophil count \<1,500/mm3)
* Refusal by a woman of childbearing potential (not post-menopausal or surgically sterile) to use a medically acceptable form of birth control (including, but not limited to, a diaphragm, an intrauterine device (IUD), progesterone implants or injections, oral contraceptives, the double-barrier method, or a condom) throughout the duration of the study
* History of hypersensitivity to anakinra or E. coli products
* Latex or rubber allergy
* Inability to give informed consent

Primary outcomes:
measure: Median Interval Change From Baseline in Peak VO2
timeFrame: 28 days
measure: Median Interval Change From Baseline in the Minute Ventilation and Carbon Dioxide Production (VE/VCO2 Slope)
timeFrame: 28 days
Secondary outcomes:
measure: Interval Change From Baseline in Biomarkers (High-sensitivity C-reactive Protein, Whole Blood Assay, Brain Natriuretic Peptide)
timeFrame: 28 days
measure: Interval Change From Baseline in Heart Failure Symptoms as Measured by Duke Activity Status Index (DASI)
timeFrame: 28 days
measure: Correlation Between Interval Changes in Biomarkers, Peak VO2, and VE/VCO2
timeFrame: 28 days
measure: Rate of Adverse Events and Hospitalizations
timeFrame: 28 days
measure: Total Exercise Time
timeFrame: 28 days
measure: Oxygen Uptake Efficiency Slope
timeFrame: 28 days
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Benjamin Van Tassell, Pharm D.
role: PRINCIPAL_INVESTIGATOR
References: