NCT01524068

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.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Sep 2012

Typical duration for phase_2

Geographic Reach
1 country

5 active sites

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 27, 2012

Completed
5 days until next milestone

First Posted

Study publicly available on registry

February 1, 2012

Completed
7 months until next milestone

Study Start

First participant enrolled

September 1, 2012

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2016

Completed
Last Updated

January 5, 2016

Status Verified

January 1, 2016

Enrollment Period

3.8 years

First QC Date

January 27, 2012

Last Update Submit

January 4, 2016

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

Acute Idiopathic Pulmonary Fibrosis ExacerbationsIdiopathic Pulmonary FibrosisIPF

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (3)

  • IgG concentrations

    Baseline to Day 60

  • B-cell counts

    Baseline to Day 60

  • Adverse event (AE) rates

    Baseline to Day 60

Study Arms (2)

Arm A - Standard Steroid Treatment

EXPERIMENTAL
Drug: Standard Steroid Treatment

Arm B - Experimental Treatment

EXPERIMENTAL
Drug: The Standard Steroid Treatment, Plasma Exchange and rituximab

Interventions

Standard Steroid TreatmentDRUG

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.

Arm A - Standard Steroid Treatment
The Standard Steroid Treatment, Plasma Exchange and rituximabDRUG

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.

Arm B - Experimental Treatment

Eligibility Criteria

Age18 Years - 90 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • Diagnosis of documented infection, thromboembolic disease, an additional etiology for acute lung injury/adult respiratory distress syndrome, congestive heart failure.
  • 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.
  • Hemodynamic instability.
  • History of reaction to blood products, murine-derived products, or prior exposures to human-murine chimeric antibodies,
  • History of malignancy.
  • Unwillingness to accept a blood transfusion.
  • Unwillingness to agree to full supportive medical care (e.g., intubation) for up to 2 weeks after enrollment.
  • Inability or unwillingness to complete post-treatment surveillance for 60 days.
  • Diagnosis of major comorbidities expected to interfere with subjects study participation for 28 days.
  • 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.).
  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Temple University Medical Center

Philladelphia, Pennsylvania, 19140, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Texas Medical Branch - Galveston

Galveston, Texas, 77555, United States

Location

Inova Fairfax Heart and Vascular Institute

Falls Church, Virginia, 22042, United States

Location

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

Plasma ExchangeRituximab

Condition Hierarchy (Ancestors)

Pulmonary FibrosisLung Diseases, InterstitialLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Blood TransfusionBiological TherapyTherapeuticsPlasmapheresisBlood Component RemovalSorption DetoxificationExtracorporeal CirculationSurgical Procedures, OperativeAntibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Steven Duncan, MD

    University of Pittsburgh

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 27, 2012

First Posted

February 1, 2012

Study Start

September 1, 2012

Primary Completion

June 1, 2016

Study Completion

June 1, 2016

Last Updated

January 5, 2016

Record last verified: 2016-01

Locations

US(5)