Combined PEX, Rituximab and Steroids in Acute IPF Exacerbations

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01266317
First received: December 22, 2010
Last updated: December 9, 2013
Last verified: December 2013

December 22, 2010
December 9, 2013
March 2011
December 2014   (final data collection date for primary outcome measure)
Feasibility and safety of the regimen in patients with IPF exacerbations [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Safety will be assessed by monitoring three variables of cardiopulmonary function:

  • Respiratory deterioration defined as PaO2 on days 0, 3, 5, 7, 14, 28 (if still hospitalized) while breathing 100% FiO2 for >20 minutes by either endotracheal tube (ETT) or nonrebreathing face mask if not intubated (face masks and O2 delivery systems for nonintubated patients will be standardized.
  • Hemodynamic deterioration defined as need for initiation of vasopressor agents, inotropes, or intravenous diuretics.
Same as current
Complete list of historical versions of study NCT01266317 on ClinicalTrials.gov Archive Site
Survival to 60 days or survival to transplantation [ Time Frame: 60 days ] [ Designated as safety issue: Yes ]
The secondary outcome measures a composite outcome defined as survival to 60 days or survival to transplantation at any time post therapy.
Same as current
Not Provided
Not Provided
 
Combined PEX, Rituximab and Steroids in Acute IPF Exacerbations
Open-Label, Feasibility Study of Combined Plasma Exchange (PEX), Rituximab, and Corticosteroids in Patients With 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 UPMC 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.
Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
IPF
Drug: Combined Plasma Exchange (PEX), Rituximab, and Corticosteroids
Standard Steroid Treatment, Plasma exchange will consist of 1.5x estimated plasma volume exchanges, Rituximab
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.

Intervention: Drug: Combined Plasma Exchange (PEX), Rituximab, and Corticosteroids
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
10
December 2014
December 2014   (final data collection date for primary outcome measure)

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 UIP.
  • 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 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.
  • Diagnosis of congestive heart failure that accounts for the hypoxemia.
  • Presence of active hepatitis B infection.
  • Coagulopathy defined as an INR > 1.8, PTT > 2 x control, and platelet count < 50K.
  • 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.
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01266317
PRO10110151
Yes
University of Pittsburgh
University of Pittsburgh
Not Provided
Principal Investigator: Michael Donahoe, MD University of Pittsburgh
University of Pittsburgh
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP