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Combined PEX, Rituximab and Steroids in Acute Idiopathic Pulmonary Fibrosis Exacerbations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01266317
Recruitment Status : Completed
First Posted : December 24, 2010
Results First Posted : January 24, 2018
Last Update Posted : March 14, 2018
Sponsor:
Information provided by (Responsible Party):
Michael Donahoe, University of Pittsburgh

Study Description
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Brief 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.


Condition or disease Intervention/treatment Phase
IPF Drug: Combined Plasma Exchange (PEX), Rituximab, and Corticosteroids Phase 1 Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-Label, Feasibility Study of Combined Plasma Exchange (PEX), Rituximab, and Corticosteroids in Patients With Acute Idiopathic Pulmonary Fibrosis Exacerbations
Study Start Date : March 2011
Actual Primary Completion Date : July 2015
Actual Study Completion Date : July 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Rituximab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Combined PEX, Rituximab and Steroids

Standard Steroid Treatment: One gm of methylprednisolone I.V., on day 0, followed by 40 mg/day I.V. on days 1-4, and days 6-12 (or the P.O. prednisone equivalent). Methylprednisolone 100 mg I.V. will be administered on days 5 and 13. Steroid doses will then be 20 mg methylprednisolone I.V. (or P.O. prednisone equivalent) from days 14-28, and then reduced thereafter at the discretion of the principle investigator.

Plasma exchange (PEX) will consist of 1.5x estimated plasma volume exchanges for 3 successive days (0, 1,2) and then, after a one day interval to enable equilibration of autoantibodies sequestered in tissues, two more daily treatments on days 4 and 5.

Rituximab: One gm I.V. will be administered on day 5 (after completion of the last PEX) and day 13.

 Drug: Combined Plasma Exchange (PEX), Rituximab, and Corticosteroids
Standard Steroid Treatment, Plasma exchange will consist of 1.5x estimated plasma volume exchanges, Rituximab


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants With Respiratory and/or Hemodynamic Deteriorations [ Time Frame: 28 days ]
    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. Respiratory deterioration was defined by a compilations of respiratory deteriorations (deteriorating gas exchange) and hemodynamic deteriorations (defined as a need for medical intervention).


Secondary Outcome Measures :
  1. Number of Participants Survived to 60 Days or to Transplantation [ Time Frame: 60 days ]
    The secondary outcome measures a composite outcome defined as survival to 60 days or survival to transplantation at any time post therapy.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01266317


Locations
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United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Michael Donahoe
Investigators
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Principal Investigator: Michael Donahoe, MD University of Pittsburgh
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Michael Donahoe, Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01266317    
Other Study ID Numbers: PRO10110151
First Posted: December 24, 2010    Key Record Dates
Results First Posted: January 24, 2018
Last Update Posted: March 14, 2018
Last Verified: February 2018
Additional relevant MeSH terms:
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Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Fibrosis
Pathologic Processes
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
 Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents