Clinical trial NCT03057028: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pulmonary Arterial Hypertension
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
First posted: 2017-02-17
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open label treatment with Anakinra
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in exercise capacity, as determined by peak oxygen consumption and ventilatory efficiency on cardiopulmonary exercise testing
timeFrame: 14 days
Secondary outcomes:
measure: Effect of anakinra on serum high sensitivity C-reactive protein
timeFrame: 14 days
measure: Effect of anakinra on serum NT-pro-BNP.
timeFrame: 14 days
measure: Effect of anakinra on serum interleukin-6
timeFrame: 14 days
measure: Change in symptoms of heart failure (as assessed by questionnaire with the Duke Activity Status Index and Minnesota Living With Heart Failure Questionnaire).
timeFrame: 14 days
measure: 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)
timeFrame: 14 days
measure: Number of patients with treatment related adverse events related to anakinra in patients with pulmonary arterial hypertension
timeFrame: 14 days
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Dan Grinnan, MD
role: PRINCIPAL_INVESTIGATOR
References: