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

• ClinicalTrials.gov Identifier: NCT03057028
• Recruitment Status: Completed
• First Posted: February 17, 2017
• Last Update Posted: April 5, 2019
• Sponsor: Virginia Commonwealth University
• Information provided by (Responsible Party): Virginia Commonwealth University

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.

Condition or disease	Intervention/treatment	Phase
Pulmonary Arterial Hypertension	Drug: Anakinra	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Open label treatment with Anakinra
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Study of the Safety and Efficacy of Anakinra in Pulmonary Arterial Hypertension
• Study Start Date: April 2016
• Actual Primary Completion Date: June 7, 2018
• Actual Study Completion Date: June 7, 2018

Arms and Interventions

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 Name: Kineret

Outcome Measures

Primary Outcome Measures :

1. Change in exercise capacity, as determined by peak oxygen consumption and ventilatory efficiency on cardiopulmonary exercise testing [ Time Frame: 14 days ]

Secondary Outcome Measures :

1. Effect of anakinra on serum high sensitivity C-reactive protein [ Time Frame: 14 days ]
2. Effect of anakinra on serum NT-pro-BNP. [ Time Frame: 14 days ]
3. Effect of anakinra on serum interleukin-6 [ Time Frame: 14 days ]
4. 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 ]
5. 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 ]
6. Number of patients with treatment related adverse events related to anakinra in patients with pulmonary arterial hypertension [ Time Frame: 14 days ]

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Virginia

Virginia Commonwealth University

Richmond, Virginia, United States, 23298

Sponsors and Collaborators

Virginia Commonwealth University

Investigators

• Principal Investigator: Dan Grinnan, MD; Virginia Commonwealth University

More Information

• Responsible Party: Virginia Commonwealth University
• ClinicalTrials.gov Identifier: NCT03057028
• Other Study ID Numbers: HM20005870
• First Posted: February 17, 2017
• Last Update Posted: April 5, 2019
• Last Verified: April 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Additional relevant MeSH terms:

Familial Primary Pulmonary Hypertension; Hypertension; Vascular Diseases; Cardiovascular Diseases; Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Interleukin 1 Receptor Antagonist Protein; Antirheumatic Agents