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

Study Overview
=================
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.

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

Conditions
-----------------
Pulmonary Hypertension

Intervention / Treatment
-----------------
* Drug: Anakinra 100 mg subcutaneously daily


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anakinra<br> | Drug: Anakinra 100 mg subcutaneously daily<br>* Anakinra 100 mg subcutaneously daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |