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A MultiCenter Study of Combined PEX, Rituximab, and Steroids in Acute Idiopathic Pulmonary Fibrosis Exacerbations

This study is not yet open for participant recruitment.
Verified June 2012 by University of Pittsburgh
Sponsor:
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01524068
First received: January 27, 2012
Last updated: June 12, 2012
Last verified: June 2012
History of Changes
  Purpose

This is a randomized, multi-center, open-label Phase II clinical trial to determine the efficacy of combined plasma exchange (PEX), rituximab, and conventional corticosteroid administration, in comparison to corticosteroids alone, among patients with acute Idiopathic Pulmonary Fibrosis (IPF) exacerbations.

The investigators central hypothesis is that antibody-mediated autoimmunity can play an important role in IPF exacerbations. The investigators propose to test our central hypothesis by establishing the efficacy of autoantibody removal by plasma exchange (PEX), in conjunction with B-cell depletion by rituximab to deplete immunoglobulins and minimize their further production, among patients with acute IPF exacerbations.

The primary goal of this randomized, multi-center, open-label Phase II clinical trial is to determine effects of combined plasma exchange (PEX), rituximab, and conventional corticosteroid administration on selected, relevant immunological parameters, in comparison to effects of steroids alone, among AE-IPF patients. The investigators anticipate the findings of this will lead to larger incremental trial(s) to determine actual clinical efficacy of this treatment.

A total of 40 subjects will be enrolled in this multi-center trial from 5 participating medical centers.


Condition Intervention Phase
Idiopathic Pulmonary Fibrosis
 Drug: Standard Steroid Treatment
Drug: The Standard Steroid Treatment, Plasma Exchange and rituximab
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open-Label, Phase II Study of Combined Plasma Exchange (PEX), Rituximab, and Corticosteroids in Patients With Acute Idiopathic Pulmonary Fibrosis Exacerbations

Resource links provided by NLM:

Drug Information available for: Rituximab
U.S. FDA Resources

Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Reduction of autoantibody titers [ Time Frame: Baseline to Day 28 ] [ Designated as safety issue: No ]
    The primary end-point is reduction of autoantibody titers to cultured human primary pulmonary cells, comparing baseline measures of each individual to results of their measures on day 28, or the latest measure among patients who do not survive to day 28.


Secondary Outcome Measures:
  • IgG concentrations [ Time Frame: Baseline to Day 60 ] [ Designated as safety issue: No ]
    Treatment-related effects on plasma IgG concentrations

  • B-cell counts [ Time Frame: Baseline to Day 60 ] [ Designated as safety issue: No ]
  • Adverse event (AE) rates [ Time Frame: Baseline to Day 60 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: September 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A - Standard Steroid Treatment Drug: 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 PI at each site.
Experimental: Arm B - Experimental Treatment Drug: The Standard Steroid Treatment, Plasma Exchange and rituximab
The Standard Steroid Treatment and, after insertion of a dialysis/apheresis catheter into a central vein, followed by initiation of the PEX and rituximab regimens.

Detailed Description:

This is a randomized, multi-center, open-label Phase II clinical trial to determine the efficacy of combined plasma exchange (PEX), rituximab, and conventional corticosteroid administration, in comparison to corticosteroids alone, among patients with acute IPF exacerbations.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  1. A diagnosis of idiopathic pulmonary fibrosis that fulfills American Thoracic Society Consensus Criteria.1
  2. Unexplained worsening or development of dyspnea or hypoxemia within the preceding 30 days.
  3. Radiographic imaging showing ground-glass abnormality and/or consolidation superimposed on a reticular or honeycomb pattern consistent with UIP.

EXCLUSION CRITERIA

  1. Diagnosis of documented infection, thromboembolic disease, an additional etiology for acute lung injury/adult respiratory distress syndrome, congestive heart failure.
  2. Presence of active hepatitis B infection.
  3. Coagulopathy defined as an INR > 1.8, PTT > 2 x control, and platelet count < 50K.
  4. Hyperosmolar state or diabetic ketoacidosis to suggest uncontrolled diabetes mellitus or uncontrolled hypertension.
  5. Hemodynamic instability.
  6. History of reaction to blood products, murine-derived products, or prior exposures to human-murine chimeric antibodies,
  7. History of malignancy.
  8. Unwillingness to accept a blood transfusion.
  9. Unwillingness to agree to full supportive medical care (e.g., intubation) for up to 2 weeks after enrollment.
  10. Inability or unwillingness to complete post-treatment surveillance for 60 days.
  11. Diagnosis of major comorbidities expected to interfere with subjects study participation for 28 days.
  12. Treatment for >5 days within the preceding month with >20 mg prednisone (or equivalent dose corticosteroid) or any treatment during the preceding month with a potent cellular immunosuppressant (e.g., cyclophosphamide, methotrexate, mycophenolate, azathiaprine, calcineurin inhibitors, etc.) unless the patient has a BAL negative for opportunistic pathogens (e.g, Pneumocystis, viruses, intracellular organisms, mycobacteria, etc.).
  13. Current treatment with an angiotensin converting enzyme inhibitor that cannot be discontinued and/or substituted with another antihypertensive agent (to minimize potential hemodynamic complications during PEX).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01524068

Locations
United States, Pennsylvania
Geisinger Medical Center Not yet recruiting
Danville, Pennsylvania, United States, 17822
Contact: Paul Simonelli, MD            
Temple University Medical Center Not yet recruiting
Philladelphia, Pennsylvania, United States, 19140
Contact: Gerald Criner, MD            
University of Pittsburgh Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Steven Duncan, MD         duncsr@upmc.edu    
United States, Texas
University of Texas Medical Branch - Galveston Not yet recruiting
Galveston, Texas, United States, 77555
Contact: Vincent Valentine, MD            
United States, Virginia
Inova Fairfax Heart and Vascular Institute Not yet recruiting
Falls Church, Virginia, United States, 22042
Contact: Steven Nathan, MD            
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Steven Duncan, MD University of Pittsburgh
  More Information

No publications provided

Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01524068     History of Changes
Other Study ID Numbers: PRO12010444
Study First Received: January 27, 2012
Last Updated: June 12, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
Acute Idiopathic Pulmonary Fibrosis Exacerbations
Idiopathic Pulmonary Fibrosis
IPF

Additional relevant MeSH terms:
Fibrosis
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Idiopathic Interstitial Pneumonias
Lung Diseases, Interstitial
 Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on May 21, 2013