Pulmonary Hypertension and Imatinib

NCT01092897 | Completed

• 1 other identifier: 09-782
• Study Type: observational
• Target: 130
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of the study is to determine whether circulating molecular and cellular biomarkers are predictive of imatinib effect on pulmonary artery hypertension.

Conditions

PAH

Outcome Measures

Primary Outcomes (1)

• Measuring circulating biomarkers of imatinib affect

  within one year of the end of the study

Secondary Outcomes (1)

• Evaluate effect of imatinib on the activation of mast cells

  within one year of the end of the study

Study Arms (1)

Subjects with PAH treated with Imatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients diagnosed with PAH that are enrolled in the Imatinib clinical trial.

You may qualify if:

• from Imatinib Trial
• Male or Female 18 years or older
• A current diagnosis or Pulmonary Arterial Hypertension according to the Dana Point 2008 Meeting: WHO Diagnostic Group I, idiopathic or heritable (familial or sporadic) PAH, PAH associated with collagen vascular disease including systemic sclerosis, rheumatoid arthritis, mixed connective tissue diseases, and overlap syndrome. PAH following one year repair of congenital heart defect (ASD, VSD, or PDA), or PAH associated with diet therapies or other drugs
• A PVR\>1000dynes.sec.cm-5(as assess by RHC at screening or in the 2 months preceding the screening visit despite treatment with two or more specific PAH therapies, including endothelin receptor antagonists (ERA), phosphodiesterase 5 inhibitors (PDE5), or inhaled, intravenous or oral prostacyclin analogues for ≥3 months. On stable background therapy doses for ≥ 30 days except for warfarin (≥30 days but doses can vary even within the mouth before enrollment)
• WHO Functional Class II-IV. For WHO Functional Class IV, one of the 2 or more specific PAH therapies must be an inhaled, intravenous or oral prostacyclin analogue, unless the subject has been shown to be intolerant of prostacyclin analogues.
• MWD≥150meters and ≥450meters at screening. Distances of two consecutive 6MWTs should be within 15% of one another.
• Ability to provide written informed consent

You may not qualify if:

• Women of childbearing potential who are not practicing birth control methods.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of positive hCG laboratory test (\> 5 mIU/MI)
• Have previously received treatment with imatinib
• In treatment with chronic nitric oxide therapy
• Pre-existing lung disease including parasitic diseases affecting lungs, congenital abnormalities of the lungs, thorax or diaphragm or bronchial asthma associated with chronic hypoxia that may contribute to severity of PAH
• With a pulmonary capillary wedge pressure \>15 mm Hg to rule out PAH secondary to left ventricular dysfunction
• With a diagnosis of pulmonary artery or vein stenosis
• With other diagnosis of PAH in WHO Diagnostic Group 1 re excluded including congenital systemic to pulmonary shunts (large, small that not surgically repaired, portal hypertension, HIV infection, glycogen storage disease, Gaucher's disease, hereditary hemorrhagic telangiectasia, hemoglobinopthaies, myeloproliferative disorders)
• With a diagnosis of PAH associated with: venous hypertension (WHO Diagnostic Group II), hypoxia (WHO Diagnostic Group III), chronic pulmonary thromboembolic disease (WHO Diagnostic Group IV) or other miscellaneous causes (WHO Diagnostic Class V, which includes sarcoidosis, histiocytosis X, lympangiomatosis, compression of pulmonary vessels).
• With deficient thrombocyte function, thrombocytopenia \>50x109/L(50x103/µL)
• With a history of acute heart failure or chronic left sided heart failure
• With uncontrolled systemic arterial hypertension, systolic \>160mmHg or diastolic \>90mmHg
• With hemoglobin \<100g/L (10 g/dl)
• With deficiencies of blood coagulation, inherited or acquired blood disorders, factor XII, factor XIII; decreased generation of coagulation factors due to acute or chronic liver diseases, efficient coagulation due to auto-antibodies against coagulation factors such as in lupus anticoagulant
• With disseminated intravascular coagulation (DIC)

Sponsors & Collaborators

• The Cleveland Clinic: lead

Study Sites (8)

University of Colorado Denver

Aurora, Colorado, United States

Location

Cleveland Clinic Florida

Weston, Florida, United States

Location

Johns Hopkins

Baltimore, Maryland, 21205, United States

Location

Tufts Medical Center

Boston, Massachusetts, United States

Location

Mayo Clinic

Rochester, Minnesota, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Location

UT Southwestern Medical Center of Dallas

Dallas, Texas, 75390-8550, United States

Location

Related Publications (5)

• Patterson KC, Weissmann A, Ahmadi T, Farber HW. Imatinib mesylate in the treatment of refractory idiopathic pulmonary arterial hypertension. Ann Intern Med. 2006 Jul 18;145(2):152-3. doi: 10.7326/0003-4819-145-2-200607180-00020. No abstract available.

  PMID: 16847299 BACKGROUND

• Schermuly RT, Dony E, Ghofrani HA, Pullamsetti S, Savai R, Roth M, Sydykov A, Lai YJ, Weissmann N, Seeger W, Grimminger F. Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest. 2005 Oct;115(10):2811-21. doi: 10.1172/JCI24838.

  PMID: 16200212 BACKGROUND

• Dentelli P, Rosso A, Balsamo A, Colmenares Benedetto S, Zeoli A, Pegoraro M, Camussi G, Pegoraro L, Brizzi MF. C-KIT, by interacting with the membrane-bound ligand, recruits endothelial progenitor cells to inflamed endothelium. Blood. 2007 May 15;109(10):4264-71. doi: 10.1182/blood-2006-06-029603. Epub 2007 Feb 8.

  PMID: 17289809 BACKGROUND

• Heath D, Yacoub M. Lung mast cells in plexogenic pulmonary arteriopathy. J Clin Pathol. 1991 Dec;44(12):1003-6. doi: 10.1136/jcp.44.12.1003.

  PMID: 1791199 BACKGROUND

• Hamada H, Terai M, Kimura H, Hirano K, Oana S, Niimi H. Increased expression of mast cell chymase in the lungs of patients with congenital heart disease associated with early pulmonary vascular disease. Am J Respir Crit Care Med. 1999 Oct;160(4):1303-8. doi: 10.1164/ajrccm.160.4.9810058.

  PMID: 10508822 BACKGROUND

Study Officials

• Kewal Asosingh, M.S., Ph.D

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Staff

Study Record Dates

• First Submitted: March 24, 2010
• First Posted: March 25, 2010
• Study Start: March 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: February 4, 2014

Record last verified: 2014-02

Locations

US (8)