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

Idiopathic Pulmonary Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01524068
• Other study ID #: PRO12010444
• Status: Withdrawn
• Phase: Phase 2
• First received: January 27, 2012
• Last updated: January 4, 2016
• Start date: September 2012
• Est. completion date: June 2016

Study information

• Verified date: January 2016
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Interstitial Pneumonias
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Inova Fairfax Heart and Vascular Institute	Falls Church	Virginia
United States	University of Texas Medical Branch - Galveston	Galveston	Texas
United States	Temple University Medical Center	Philladelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pittsburgh

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction of autoantibody titers	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.	Baseline to Day 28	No
Secondary	IgG concentrations	Treatment-related effects on plasma IgG concentrations	Baseline to Day 60	No
Secondary	B-cell counts		Baseline to Day 60	No
Secondary	Adverse event (AE) rates		Baseline to Day 60	Yes