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Pilot Study of the Safety and Efficacy of Anakinra in Pulmonary Arterial Hypertension

Phase 1
Completed
Conditions
Pulmonary Arterial Hypertension
Interventions
Registration Number
NCT03057028
Lead Sponsor
Virginia Commonwealth University
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
7
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
anakinraAnakinraPatients 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.
Primary Outcome Measures
NameTimeMethod
Change in exercise capacity, as determined by peak oxygen consumption and ventilatory efficiency on cardiopulmonary exercise testing14 days
Secondary Outcome Measures
NameTimeMethod
Effect of anakinra on serum high sensitivity C-reactive protein14 days
Effect of anakinra on serum NT-pro-BNP.14 days
Effect of anakinra on serum interleukin-614 days
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)14 days
Change in symptoms of heart failure (as assessed by questionnaire with the Duke Activity Status Index and Minnesota Living With Heart Failure Questionnaire).14 days
Number of patients with treatment related adverse events related to anakinra in patients with pulmonary arterial hypertension14 days

Trial Locations

Locations (1)

Virginia Commonwealth University

🇺🇸

Richmond, Virginia, United States

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