Pilot Study of the Safety and Efficacy of Anakinra (Recombinant Human Interleukin-1 Receptor Antagonist) in Pulmonary Hypertension
Primary Purpose
Pulmonary Hypertension
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Anakinra 100 mg subcutaneously daily
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Hypertension
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
Sites / Locations
- Virginia Commonwealth University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Anakinra
Arm Description
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Interval Change From Baseline in Biomarkers (High-sensitivity C-reactive Protein, Whole Blood Assay, Brain Natriuretic Peptide)
Interval Change From Baseline in Heart Failure Symptoms as Measured by Duke Activity Status Index (DASI)
Correlation Between Interval Changes in Biomarkers, Peak VO2, and VE/VCO2
Rate of Adverse Events and Hospitalizations
Total Exercise Time
Oxygen Uptake Efficiency Slope
Full Information
NCT ID
NCT01479010
First Posted
November 7, 2011
Last Updated
October 9, 2017
Sponsor
Virginia Commonwealth University
1. Study Identification
Unique Protocol Identification Number
NCT01479010
Brief Title
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
2. Study Status
Record Verification Date
October 2017
Overall Recruitment Status
Terminated
Why Stopped
recruitment issues, critical investigators left institution
Study Start Date
November 2011 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
November 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Virginia Commonwealth University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Hypertension
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Anakinra
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Anakinra 100 mg subcutaneously daily
Intervention Description
Anakinra 100 mg subcutaneously daily
Primary Outcome Measure Information:
Title
Median Interval Change From Baseline in Peak VO2
Description
Peak VO2 will be measured during a standardized cardiopulmonary exercise test in which patients exercise on a treadmill while breathing through a mask.
Time Frame
28 days
Title
Median Interval Change From Baseline in the Minute Ventilation and Carbon Dioxide Production (VE/VCO2 Slope)
Description
VE/VCO2 slope will be measured during a standardized cardiopulmonary exercise test in which patients exercise on a treadmill while breathing through a mask.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Interval Change From Baseline in Biomarkers (High-sensitivity C-reactive Protein, Whole Blood Assay, Brain Natriuretic Peptide)
Time Frame
28 days
Title
Interval Change From Baseline in Heart Failure Symptoms as Measured by Duke Activity Status Index (DASI)
Time Frame
28 days
Title
Correlation Between Interval Changes in Biomarkers, Peak VO2, and VE/VCO2
Time Frame
28 days
Title
Rate of Adverse Events and Hospitalizations
Time Frame
28 days
Title
Total Exercise Time
Time Frame
28 days
Title
Oxygen Uptake Efficiency Slope
Time Frame
28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benjamin Van Tassell, Pharm D.
Organizational Affiliation
Virginia Commonwealth University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Pilot Study of the Safety and Efficacy of Anakinra (Recombinant Human Interleukin-1 Receptor Antagonist) in Pulmonary Hypertension
We'll reach out to this number within 24 hrs