IPFPhase 1/2NCT01266317
Combined PEX, Rituximab and Steroids in Acute Idiopathic Pulmonary Fibrosis Exacerbations
A Phase 1/2 study testing Combined Plasma Exchange (PEX), Rituximab, and Corticosteroids in people with IPF, run by Michael Donahoe at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- IPF
- What is being tested?
- Combined Plasma Exchange (PEX), Rituximab, and Corticosteroids
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2011to Jul 2015
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Open-Label, Feasibility Study of Combined Plasma Exchange (PEX), Rituximab, and Corticosteroids in Patients With Acute Idiopathic Pulmonary Fibrosis Exacerbations
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:
- 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.
- 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:
- 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 UIP.
- 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
- Diagnosis of documented infection based upon clinical evaluation and microbial testing.
- Diagnosis of thromboembolic disease by clinical assessment.
- 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.
- Diagnosis of congestive heart failure that accounts for the hypoxemia.
- 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 (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.
- Conditions
- IPF
- Being tested
- Combined Plasma Exchange (PEX), Rituximab, and Corticosteroids
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combined Plasma Exchange (PEX), Rituximab, and CorticosteroidsDrug
Standard Steroid Treatment, Plasma exchange will consist of 1.5x estimated plasma volume exchanges, Rituximab
| Study group | Role | What they receive |
|---|---|---|
| Combined PEX, Rituximab and Steroids | Experimental | 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. Receives: Drug: Combined Plasma Exchange (PEX), Rituximab, and Corticosteroids |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2010 (estimated)
- Study startMar 2011
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for IPFStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michael Donahoe
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Michael Donahoe, University of Pittsburgh
- Investigators
- Michael Donahoe, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01266317
- Sponsor's protocol ID
- PRO10110151
- Status last verified
- Feb 2018
- First submitted
- 22 Dec 2010
- Last updated
- 14 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 26083430
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-Label, Feasibility Study of Combined Plasma Exchange (PEX), Rituximab, and Corticosteroids in Patients With Acute Idiopathic Pulmonary Fibrosis Exacerbations
- ClinicalTrials.gov ID
- NCT01266317
- Acronym / sponsor ID
- PRO10110151
- Conditions
- IPF
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Michael DonahoeUniversity, hospital or other
- Study start
- Mar 2011
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 24 Dec 2010 (estimated)
- Results
- Posted 24 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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.
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:
- 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 UIP.
- 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
- Diagnosis of documented infection based upon clinical evaluation and microbial testing.
- Diagnosis of thromboembolic disease by clinical assessment.
- 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.
- Diagnosis of congestive heart failure that accounts for the hypoxemia.
- 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 (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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combined PEX, Rituximab and Steroids | Experimental | Drug: Combined Plasma Exchange (PEX), Rituximab, and CorticosteroidsStandard 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Combined Plasma Exchange (PEX), Rituximab, and CorticosteroidsStandard Steroid Treatment, Plasma exchange will consist of 1.5x estimated plasma volume exchanges, Rituximab | Drug | Combined PEX, Rituximab and Steroids |
Primary outcome
Number of Participants With Respiratory and/or Hemodynamic Deteriorations
Time frame: 28 days
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).
1 secondary outcome
Number of Participants Survived to 60 Days or to Transplantation
Time frame: 60 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26083430Donahoe 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Donahoe, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Combined Plasma Exchange (PEX), Rituximab, and Corticosteroids in people with IPF, run by Michael Donahoe at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Respiratory and/or Hemodynamic Deteriorations (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01266317, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2018.