Pulmonary Hypertension
Conditions
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.
Interventions
DRUGAnakinra 100 mg subcutaneously daily
Anakinra 100 mg subcutaneously daily
Sponsors
Virginia Commonwealth University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| Correlation Between Interval Changes in Biomarkers, Peak VO2, and VE/VCO2 | 28 days |
| Rate of Adverse Events and Hospitalizations | 28 days |
| Interval Change From Baseline in Biomarkers (High-sensitivity C-reactive Protein, Whole Blood Assay, Brain Natriuretic Peptide) | 28 days |
| Oxygen Uptake Efficiency Slope | 28 days |
| Total Exercise Time | 28 days |
| Interval Change From Baseline in Heart Failure Symptoms as Measured by Duke Activity Status Index (DASI) | 28 days |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anakinra Anakinra 100 mg subcutaneously daily: Anakinra 100 mg subcutaneously daily | 0 |
| Total | 0 |
Baseline characteristics
| Characteristic | — |
|---|---|
| Region of Enrollment United States | — participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
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.
Time frame: 28 days
Population: Due to the small number of participants, results are not included to protect the privacy of individual participants.
Primary
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.
Time frame: 28 days
Population: Due to the small number of participants, results are not included to protect the privacy of individual participants.
Secondary
Correlation Between Interval Changes in Biomarkers, Peak VO2, and VE/VCO2
Time frame: 28 days
Population: Due to the small number of participants, results are not included to protect the privacy of individual participants.
Secondary
Interval Change From Baseline in Biomarkers (High-sensitivity C-reactive Protein, Whole Blood Assay, Brain Natriuretic Peptide)
Time frame: 28 days
Population: Due to the small number of participants, results are not included to protect the privacy of individual participants.
Secondary
Interval Change From Baseline in Heart Failure Symptoms as Measured by Duke Activity Status Index (DASI)
Time frame: 28 days
Population: Due to the small number of participants, results are not included to protect the privacy of individual participants.
Secondary
Oxygen Uptake Efficiency Slope
Time frame: 28 days
Population: Due to the small number of participants, results are not included to protect the privacy of individual participants.
Secondary
Rate of Adverse Events and Hospitalizations
Time frame: 28 days
Population: Due to the small number of participants, results are not included to protect the privacy of individual participants.
Secondary
Total Exercise Time
Time frame: 28 days
Population: Due to the small number of participants, results are not included to protect the privacy of individual participants.