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Pilot Study of the Safety and Efficacy of Anakinra (Recombinant Human Interleukin-1 Receptor Antagonist) in Pulmonary Hypertension

This study has been terminated.
(recruitment issues, critical investigators left institution)
Sponsor:
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT01479010
First received: November 7, 2011
Last updated: March 4, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Pulmonary Hypertension
Drug: Anakinra 100 mg subcutaneously daily
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of the Safety and Efficacy of Anakinra (Recombinant Human Interleukin-1 Receptor Antagonist) in Pulmonary Hypertension

Resource links provided by NLM:


Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • Median interval change from baseline in peak VO2 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Interval change from baseline in biomarkers (high-sensitivity C-reactive protein, whole blood assay, brain natriuretic peptide) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Interval change from baseline in heart failure symptoms as measured by Duke Activity Status Index (DASI) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Correlation between interval changes in biomarkers, peak VO2, and VE/VCO2 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Rate of adverse events and hospitalizations [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Total exercise time [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Oxygen uptake efficiency slope [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Enrollment: 2
Study Start Date: November 2011
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anakinra Drug: Anakinra 100 mg subcutaneously daily
Anakinra 100 mg subcutaneously daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01479010

Locations
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Virginia Commonwealth University
Investigators
Principal Investigator: Benjamin Van Tassell, Pharm D. Virginia Commonwealth University
  More Information

No publications provided

Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT01479010     History of Changes
Other Study ID Numbers: HM13729
Study First Received: November 7, 2011
Last Updated: March 4, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014