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CompletedNCT01266317Updated Mar 14, 2018Results posted

Combined PEX, Rituximab and Steroids in Acute Idiopathic Pulmonary Fibrosis Exacerbations

A Phase 1/2 interventional study of Combined Plasma Exchange (PEX), Rituximab, and Corticosteroids in IPF, sponsored by Michael Donahoe. Completed at 1 site in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2018-03-14.

Sponsored by Michael Donahoe · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
9
Allocation
Not applicable
Ages
18 Years to 80 Years
Sex
All
01

Study summary

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 University of Pittsburgh Medical Center will be enrolled in this study.

Read the detailed description

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.
02

Conditions studied

  • IPF
03

In context

Pulmonary Fibrosis

680 studies on the registry are indexed under Pulmonary Fibrosis; 119 are open to participants now.

This study's enrollment of 9 is below the median of 50 across 419 interventional studies indexed under Pulmonary Fibrosis.

Browse Pulmonary Fibrosis studies →

Lead sponsor

Michael Donahoe is the lead sponsor of 2 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

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 usual interstitial pneumonia.
  • 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

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 Acute Lung Injury/Acute Respiratory Distress Syndrome 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 International Normalized Ratio > 1.8, Partial Thromboplastin Time > 2 x control, and platelet count \< 50,000.
  • 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.
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
9 participants (actual)

Study arms

  • 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.

    Drug: Combined Plasma Exchange (PEX), Rituximab, and Corticosteroids

Interventions

  • DrugCombined Plasma Exchange (PEX), Rituximab, and Corticosteroids

    Standard Steroid Treatment, Plasma exchange will consist of 1.5x estimated plasma volume exchanges, Rituximab

06

What researchers measure

Primary outcomes

  1. Number of Participants With Respiratory and/or Hemodynamic Deteriorations

    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. Respiratory deterioration was defined by a compilations of respiratory deteriorations (deteriorating gas exchange) and hemodynamic deteriorations (defined as a need for medical intervention).

    Time frame: 28 days

Secondary outcomes

  1. Number of Participants Survived to 60 Days or to Transplantation

    The secondary outcome measures a composite outcome defined as survival to 60 days or survival to transplantation at any time post therapy.

    Time frame: 60 days

07

Results

Posted Jan 24, 2018
Limitations and caveats
This was a pilot, open-label trial of an unprecedented regimen for a highly lethal disease and, as such, included only small numbers of subjects and historical controls.

Participant flow

Participant flow — Overall Study
MilestoneCombined PEX, Rituximab and Steroids
Started9
Completed7
Not completed2
Withdrew: Withdrawal by subject2

Outcome measures

PrimaryNumber of Participants With Respiratory and/or Hemodynamic Deteriorations

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. Respiratory deterioration was defined by a compilations of respiratory deteriorations (deteriorating gas exchange) and hemodynamic deteriorations (defined as a need for medical intervention).

Time frame:
28 days
Reported as:
Count of participants · Participants
Number of Participants With Respiratory and/or Hemodynamic Deteriorations
ParticipantsCombined PEX, Rituximab and Steroids
Respiratory Deterioration1
Hemodynamic Deterioration3
SecondaryNumber of Participants Survived to 60 Days or to Transplantation

The secondary outcome measures a composite outcome defined as survival to 60 days or survival to transplantation at any time post therapy.

Time frame:
60 days
Reported as:
Count of participants · Participants
Number of Participants Survived to 60 Days or to Transplantation
ParticipantsCombined PEX, Rituximab and Steroids
Number of Participants Survived to 60 Days or to Transplantation3

Adverse events

Collected over 60 days. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Combined PEX, Rituximab and Steroids—1/10 (10%)4/10 (40%)
Most frequent serious events
Most frequent serious events
EventCombined PEX, Rituximab and Steroids
HypoxemiaRespiratory, thoracic and mediastinal disorders1/10
Most frequent other events
Most frequent other events
EventCombined PEX, Rituximab and Steroids
HypoxemiaRespiratory, thoracic and mediastinal disorders4/10
HypotensionVascular disorders1/10
HyperglycemiaEndocrine disorders1/10
RashSkin and subcutaneous tissue disorders1/10
InfectionSkin and subcutaneous tissue disorders1/10

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Combined PEX, Rituximab and Steroids
<=18 years0
Between 18 and 65 years3
>=65 years6
Sex: Female, Male
Sex: Female, Male(Participants)Combined PEX, Rituximab and Steroids
Female3
Male6
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Combined PEX, Rituximab and Steroids
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White9
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Combined PEX, Rituximab and Steroids
United States9
08

Study locations

1 site
  • University of Pittsburgh Medical Center
    Pittsburgh, Pennsylvania 15213, United States
09

References and documents

Publications

  • Donahoe M, Valentine VG, Chien N, Gibson KF, Raval JS, Saul M, Xue J, Zhang Y, Duncan SR. Autoantibody-Targeted Treatments for Acute Exacerbations of Idiopathic Pulmonary Fibrosis. PLoS One. 2015 Jun 17;10(6):e0127771. doi: 10.1371/journal.pone.0127771. eCollection 2015. Erratum In: PLoS One. 2015 Jul 20;10(7):e0133684. doi: 10.1371/journal.pone.0133684. PubMed 26083430 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 14, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01266317
Lead sponsor
Michael Donahoe
Responsible party
Michael Donahoe (Professor, University of Pittsburgh) — Sponsor-investigator
First posted
Dec 24, 2010
Start date
Mar 2011
Primary completion
Jul 2015
Completion
Jul 2015
Results posted
Jan 24, 2018
Last update
Mar 14, 2018

Study contacts

Michael Donahoe, MD
principal investigator · University of Pittsburgh

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Feb 2018. You cannot join it, but the record below documents what was studied.

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