Combined PEX, Rituximab and Steroids in Acute Idiopathic Pulmonary Fibrosis Exacerbations
Combined PEX, Rituximab and Steroids in Acute Idiopathic Pulmonary Fibrosis Exacerbations
This is an open-label Phase I/II trial to assess the feasibility and safety of combined
 plasma exchange (PEX), rituximab, and conventional corticosteroid administration on the
 outcome of hospitalized patients with acute IPF exacerbations. The specific aims of this
 study are:

 1. To assess the feasibility and safety of combined PEX, rituximab, and conventional
 corticosteroid administrations for the treatment of hospitalized patients with acute IPF
 exacerbations by monitoring indices of respiratory (PaO2) and cardiovascular function
 during the treatment interval.

 2. To assess the efficacy of combined PEX, rituximab, and conventional corticosteroid
 administrations for the treatment of hospitalized patients with acute IPF exacerbations
 on patient survival in comparison to historical controls. Patient survival for this
 investigation will be defined using the composite outcome of 60 day survival and/or
 survival to lung transplantation.

 Subjects between 18 and 80 years of age who have a confirmed diagnosis of IPF, and meet all
 the study requirements will be enrolled in this study. A total of 10 subjects of both genders
 and all ethnic backgrounds with acute IPF exacerbations hospitalized at University of
 Pittsburgh Medical Center will be enrolled in this study.
This is a prospective, open-label Phase II, non-randomized clinical trial to assess the
 feasibility and safety of combined plasma exchange (PEX), rituximab, and conventional
 corticosteroid administration in patients with acute IPF exacerbations.

 INCLUSION CRITERIA:

 1. A diagnosis of idiopathic pulmonary fibrosis that fulfills American Thoracic Society
 Consensus Criteria.

 2. Unexplained worsening or development of dyspnea or hypoxemia within 30 days leading to
 the current hospitalization.

 3. Radiographic imaging showing ground-glass abnormality and/or consolidation superimposed
 on a background of reticular or honeycomb pattern consistent with UIP.

 4. Intent on the part of the treating physician to use high dose steroid therapy as a
 therapeutic effort to treat a diagnosis of acute IPF exacerbation.

 EXCLUSION CRITERIA

 1. Diagnosis of documented infection based upon clinical evaluation and microbial testing.

 2. Diagnosis of thromboembolic disease by clinical assessment.

 3. Diagnosis of an additional etiology for ALI/ARDS based upon clinical assessment to
 include sepsis, aspiration, trauma, inhalational injury, acute pancreatitis, drug
 toxicity, blood product transfusion reaction, or stem cell transplantation.

 4. Diagnosis of congestive heart failure that accounts for the hypoxemia.

 5. Presence of active hepatitis B infection.

 6. Coagulopathy defined as an INR > 1.8, PTT > 2 x control, and platelet count < 50K.

 7. Hyperosmolar state or diabetic ketoacidosis to suggest uncontrolled diabetes mellitus or
 uncontrolled hypertension (systolic BP > 160 mm Hg and diastolic BP > 100 mm Hg) which
 would contraindicated the use of corticosteroids.

 8. Hemodynamic instability defined as a vasopressor requirement which would contraindicate
 the use of plasmapheresis.

 9. History of reaction to blood products, murine-derived products, or prior exposures to
 human-murine chimeric antibodies,

 10. History of malignancy.

 11. Inability or unwillingness to accept a blood transfusion.

 12. Inability or unwillingness to complete post- treatment surveillance for 60 days.

 13. Diagnosis of major comorbidities expected to interfere with subjects study participation
 for 60 days.
Inclusion Criteria:

 -  A diagnosis of idiopathic pulmonary fibrosis that fulfills American Thoracic Society
 Consensus Criteria.

 -  Unexplained worsening or development of dyspnea or hypoxemia within 30 days leading to
 the current hospitalization.

 -  Radiographic imaging showing ground-glass abnormality and/or consolidation
 superimposed on a background of reticular or honeycomb pattern consistent with usual
 interstitial pneumonia.

 -  Intent on the part of the treating physician to use high dose steroid therapy as a
 therapeutic effort to treat a diagnosis of acute IPF exacerbation.

 Exclusion Criteria:

 -  Diagnosis of documented infection based upon clinical evaluation and microbial
 testing.

 -  Diagnosis of thromboembolic disease by clinical assessment.

 -  Diagnosis of an additional etiology for Acute Lung Injury/Acute Respiratory Distress
 Syndrome based upon clinical assessment to include sepsis, aspiration, trauma,
 inhalational injury, acute pancreatitis, drug toxicity, blood product transfusion
 reaction, or stem cell transplantation.

 -  Diagnosis of congestive heart failure that accounts for the hypoxemia.

 -  Presence of active hepatitis B infection.

 -  Coagulopathy defined as an International Normalized Ratio > 1.8, Partial
 Thromboplastin Time > 2 x control, and platelet count < 50,000.

 -  Hyperosmolar state or diabetic ketoacidosis to suggest uncontrolled diabetes mellitus
 or uncontrolled hypertension (systolic BP > 160 mm Hg and diastolic BP > 100 mm Hg)
 which would contraindicated the use of corticosteroids.

 -  Hemodynamic instability defined as a vasopressor requirement which would
 contraindicate the use of plasmapheresis.

 -  History of reaction to blood products, murine-derived products, or prior exposures to
 human-murine chimeric antibodies,

 -  History of malignancy.

 -  Inability or unwillingness to accept a blood transfusion.

 -  Inability or unwillingness to complete post- treatment surveillance for 60 days.

 -  Diagnosis of major comorbidities expected to interfere with subjects study
 participation for 60 days.