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

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.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Hypertension
• Intervention / Treatment: Drug: Anakinra 100 mg subcutaneously daily

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anakinra	Drug: Anakinra 100 mg subcutaneously daily; Anakinra 100 mg subcutaneously daily

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	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

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Investigators: Principal Investigator: Benjamin Van Tassell, Pharm D., Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: November 7, 2011
• First Submitted That Met QC Criteria: November 21, 2011
• First Posted (Estimate): November 24, 2011

Study Record Updates

• Last Update Posted (Actual): November 13, 2017
• Last Update Submitted That Met QC Criteria: October 9, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Antirheumatic Agents; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: HM13729