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

Phase 1

Terminated

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Anakinra	Anakinra 100 mg subcutaneously daily	-

Primary Outcome Measures

Name	Time	Method
Median Interval Change From Baseline in Peak VO2	28 days	Peak VO2 will be measured during a standardized cardiopulmonary exercise test in which patients exercise on a treadmill while breathing through a mask.
Median Interval Change From Baseline in the Minute Ventilation and Carbon Dioxide Production (VE/VCO2 Slope)	28 days	VE/VCO2 slope will be measured during a standardized cardiopulmonary exercise test in which patients exercise on a treadmill while breathing through a mask.

Secondary Outcome Measures

Name	Time	Method
Interval Change From Baseline in Biomarkers (High-sensitivity C-reactive Protein, Whole Blood Assay, Brain Natriuretic Peptide)	28 days
Interval Change From Baseline in Heart Failure Symptoms as Measured by Duke Activity Status Index (DASI)	28 days
Correlation Between Interval Changes in Biomarkers, Peak VO2, and VE/VCO2	28 days
Rate of Adverse Events and Hospitalizations	28 days
Total Exercise Time	28 days
Oxygen Uptake Efficiency Slope	28 days