Combined PEX, Rituximab and Steroids in Acute Idiopathic Pulmonary Fibrosis Exacerbations
Condition: IPF
MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Combined Plasma Exchange (PEX), Rituximab, and Corticosteroids
Intervention type(s): Drug
Intervention description(s): Standard Steroid Treatment, Plasma exchange will consist of 1.5x estimated plasma volume exchanges, Rituximab
Intervention MeSH terms: Rituximab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment