Pilot Study of the Safety and Efficacy of Anakinra in Pulmonary Arterial Hypertension
Primary Purpose
Pulmonary Arterial Hypertension
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Anakinra
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension
Eligibility Criteria
Inclusion Criteria:
- age over 18
- functional class II or III symptoms of right ventricular failure despite optimal PAH therapy
- mean pulmonary artery pressure >25mmHg on previous right heart catheterization
- pulmonary arterial wedge pressure <15mmHg on previous right heart catheterization
- pulmonary vascular resistance >3 wood units on previous right heart catheterization
Exclusion Criteria:
- PAH due to connective tissue disease
- angina or electrocardiograph changes that limit maximum exertion during cardiopulmonary exercise testing or baseline EKG changes that limit the ability to detect ischemia
- recent (<14 days) use of anti-inflammatory drugs (not including NSAIDs), chronic inflammatory disorder, malignancy, active infection, or any comorbidity limiting survival or ability to complete the study
- sever kidney dysfunction (eGFR <30mL/min)
- thrombocytopenia (<50,000/mm3), or neutropenia (absolute neutrophil count <1500/mm3)
- refusal by a woman of childbearing potential to use a medically acceptable form of birth control
- history of hypersensitivity to anakinra or E. coli products
- latex or rubber allergy
- inability to give informed consent
- non-English speaking
Sites / Locations
- Virginia Commonwealth University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
anakinra
Arm Description
Patients will be treated with anakinra, injected SQ daily in a dose of 100mg for 14 days. Before and after this intervention, patients will undergo cardiopulmonary exercise testing (as well as echocardiography, EKG analysis, and serologic analysis). Subjects will be assessed for changes in exercise capacity, as determined by peak oxygen uptake and ventilatory efficiency to CO2 production slope.
Outcomes
Primary Outcome Measures
Change in exercise capacity, as determined by peak oxygen consumption and ventilatory efficiency on cardiopulmonary exercise testing
Secondary Outcome Measures
Effect of anakinra on serum high sensitivity C-reactive protein
Effect of anakinra on serum NT-pro-BNP.
Effect of anakinra on serum interleukin-6
Change in symptoms of heart failure (as assessed by questionnaire with the Duke Activity Status Index and Minnesota Living With Heart Failure Questionnaire).
Correlate between biomarkers (serum high sensitivity C reactive protein, interluekin-6, and NT-pro BNP) and measures of exercise capacity (peak oxygen consumption and ventilatory efficiency on cardiopulmonary exercise testing)
Number of patients with treatment related adverse events related to anakinra in patients with pulmonary arterial hypertension
Full Information
NCT ID
NCT03057028
First Posted
May 4, 2016
Last Updated
April 4, 2019
Sponsor
Virginia Commonwealth University
1. Study Identification
Unique Protocol Identification Number
NCT03057028
Brief Title
Pilot Study of the Safety and Efficacy of Anakinra in Pulmonary Arterial Hypertension
Official Title
Pilot Study of the Safety and Efficacy of Anakinra in Pulmonary Arterial Hypertension
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
April 2016 (undefined)
Primary Completion Date
June 7, 2018 (Actual)
Study Completion Date
June 7, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Virginia Commonwealth University
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Pulmonary arterial hypertension (PAH) can result in right ventricular failure and death. Anakinra has been used in patients with left sided heart failure, and the present study looks to determine if anakinra is safe and effective in patients with PAH. To accomplish this goal, we plan to evaluate for exercise improvement (as assessed by cardiopulmonary exercise testing) in 10 patients with PAH on anakinra.
Detailed Description
Patients with pulmonary arterial hypertension will undergo cardiopulmonary exercise testing (CPET) at baseline and at 2 weeks. After the initial CPET, all patients will receive anakinra as a daily injection for 2 weeks. Patients will be instructed in the use of anakinra during their initial visit. Our primary outcome will be the difference in the exercise capacity of patients with PAH, as measured by maximal uptake of oxygen on CPET.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Open label treatment with Anakinra
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
anakinra
Arm Type
Experimental
Arm Description
Patients will be treated with anakinra, injected SQ daily in a dose of 100mg for 14 days. Before and after this intervention, patients will undergo cardiopulmonary exercise testing (as well as echocardiography, EKG analysis, and serologic analysis). Subjects will be assessed for changes in exercise capacity, as determined by peak oxygen uptake and ventilatory efficiency to CO2 production slope.
Intervention Type
Drug
Intervention Name(s)
Anakinra
Other Intervention Name(s)
Kineret
Primary Outcome Measure Information:
Title
Change in exercise capacity, as determined by peak oxygen consumption and ventilatory efficiency on cardiopulmonary exercise testing
Time Frame
14 days
Secondary Outcome Measure Information:
Title
Effect of anakinra on serum high sensitivity C-reactive protein
Time Frame
14 days
Title
Effect of anakinra on serum NT-pro-BNP.
Time Frame
14 days
Title
Effect of anakinra on serum interleukin-6
Time Frame
14 days
Title
Change in symptoms of heart failure (as assessed by questionnaire with the Duke Activity Status Index and Minnesota Living With Heart Failure Questionnaire).
Time Frame
14 days
Title
Correlate between biomarkers (serum high sensitivity C reactive protein, interluekin-6, and NT-pro BNP) and measures of exercise capacity (peak oxygen consumption and ventilatory efficiency on cardiopulmonary exercise testing)
Time Frame
14 days
Title
Number of patients with treatment related adverse events related to anakinra in patients with pulmonary arterial hypertension
Time Frame
14 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
age over 18
functional class II or III symptoms of right ventricular failure despite optimal PAH therapy
mean pulmonary artery pressure >25mmHg on previous right heart catheterization
pulmonary arterial wedge pressure <15mmHg on previous right heart catheterization
pulmonary vascular resistance >3 wood units on previous right heart catheterization
Exclusion Criteria:
PAH due to connective tissue disease
angina or electrocardiograph changes that limit maximum exertion during cardiopulmonary exercise testing or baseline EKG changes that limit the ability to detect ischemia
recent (<14 days) use of anti-inflammatory drugs (not including NSAIDs), chronic inflammatory disorder, malignancy, active infection, or any comorbidity limiting survival or ability to complete the study
sever kidney dysfunction (eGFR <30mL/min)
thrombocytopenia (<50,000/mm3), or neutropenia (absolute neutrophil count <1500/mm3)
refusal by a woman of childbearing potential to use a medically acceptable form of birth control
history of hypersensitivity to anakinra or E. coli products
latex or rubber allergy
inability to give informed consent
non-English speaking
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dan Grinnan, MD
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
Plan to Share IPD
Undecided
Learn more about this trial
Pilot Study of the Safety and Efficacy of Anakinra in Pulmonary Arterial Hypertension
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