Clinical trial NCT01524068: A MultiCenter Study of Combined PEX, Rituximab, and Steroids in Acute Idiopathic Pulmonary Fibrosis Exacerbations
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: Acute Idiopathic Pulmonary Fibrosis Exacerbations
Idiopathic Pulmonary Fibrosis
IPF
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2012-02-01
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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).

Primary outcomes:
measure: Reduction of autoantibody titers
timeFrame: Baseline to Day 28
Secondary outcomes:
measure: IgG concentrations
timeFrame: Baseline to Day 60
measure: B-cell counts
timeFrame: Baseline to Day 60
measure: Adverse event (AE) rates
timeFrame: Baseline to Day 60
Other outcomes:
Locations:
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Philladelphia
country: United States
facility: Temple University Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Galveston
country: United States
facility: University of Texas Medical Branch - Galveston
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax Heart and Vascular Institute
state: Virginia
Study officials:
affiliation: University of Pittsburgh
name: Steven Duncan, MD
role: PRINCIPAL_INVESTIGATOR
References: