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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: anakinra; 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.

Drug: Anakinra; Other Names: Kineret

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in exercise capacity, as determined by peak oxygen consumption and ventilatory efficiency on cardiopulmonary exercise testing	14 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Effect of anakinra on serum high sensitivity C-reactive protein	14 days
Effect of anakinra on serum NT-pro-BNP.	14 days
Effect of anakinra on serum interleukin-6	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
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
Number of patients with treatment related adverse events related to anakinra in patients with pulmonary arterial hypertension	14 days

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Investigators: Principal Investigator: Dan Grinnan, MD, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): June 7, 2018
• Study Completion (Actual): June 7, 2018

Study Registration Dates

• First Submitted: May 4, 2016
• First Submitted That Met QC Criteria: February 14, 2017
• First Posted (Actual): February 17, 2017

Study Record Updates

• Last Update Posted (Actual): April 5, 2019
• Last Update Submitted That Met QC Criteria: April 4, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Antirheumatic Agents; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: HM20005870

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED