Therapeutic Plasma Exchange, Rituximab and IV Ig for Severe Acute Exacerbation of IPF Admitted in ICU (EXCHANGE-IPF)
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ClinicalTrials.gov Identifier: NCT03584802 |
Recruitment Status :
Recruiting
First Posted : July 12, 2018
Last Update Posted : June 11, 2020
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Condition or disease | Intervention/treatment | Phase |
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Exacerbation of Idiopathic Pulmonary Fibrosis | Other: Therapeutic plasma exchanges Other: Conventional treatment of AE-IPF | Not Applicable |

Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 40 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Therapeutic Plasma Exchange, Rituximab and Intravenous Immunoglobulins for Severe Acute Exacerbation of Idiopathic Pulmonary Fibrosis Admitted in ICU: an Open, Randomized, Controlled Trial |
Actual Study Start Date : | May 16, 2019 |
Estimated Primary Completion Date : | October 1, 2020 |
Estimated Study Completion Date : | March 1, 2021 |

Arm | Intervention/treatment |
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Experimental: Experimental treatment of AE-IPF
The experimental group will receive a combination of: 1- Methylprednisolone bolus of 1g IV day 1, then 20 mg/day (or oral prednisolone equivalent) for 21 days; 2- Nine therapeutic plasma exchanges of 1,5x the estimated plasma volumes using albumin: saline (3:1) or fresh frozen plasma in case of an INR superior to 1,5, on days 1,2,3,5,7,9,11,13,15; followed by administration of low dose of intravenous immunoglobulin (100mg/kg) 3, Rituximab 1g IV on days 7 and 15 (after therapeutic plasma exchange and premedication) 4, Intravenous immunoglobulin 0,5g/kg/d on days 16 to 19,
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Other: Therapeutic plasma exchanges
The patient will initially receive Methylprednisolone bolus of 1g i.v. day 1, then 20 mg/day (or oral prednisone equivalent) for 21 days; and then he will have nine therapeutic plasma exchanges of 1.5x the estimated plasma volumes using albumin:saline (3:1) or fresh frozen plasma in case of an INR superior to 1.5, on days 1,2,3,5,7,9,11,13,15; followed by administration of low dose of intravenous immunoglobulin (100 mg/kg). On days 7 and 15, the patient will receive rituximab 1 g i.v. on days 7 and 15 (after therapeutic plasma exchange and premedication); and intravenous immunoglobulin 0.5 g/kg/d on days 16 to 19. |
Active Comparator: Conventional treatment of AE-IPF
Intravenous methylprednisolone bolus of 10mg/kg on day1, 2 and 3, then 1mg/kg/d for 1 week, and 0,75 mg/kg/d for 1 week, then 0,5 mg/kg/d for 1 week, and 0,25 mg/kg/d for 1 week, and 0,125 mg/kg/d until day 90. Shift to oral prednisone as soon as the oral route is available.
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Other: Conventional treatment of AE-IPF
Conventional treatment of AE-IPF |
- Overall mortality at day 28 after initiation of therapy (Day1) [ Time Frame: 28 days ]Overall mortality at day 28 after initiation of therapy (Day1)
- Overall mortality at 12 months [ Time Frame: 12 months ]Overall mortality at 12 months
- Number of days alive without mechanical ventilation between day 1 and day 28 [ Time Frame: 28 days ]Number of days alive without mechanical ventilation
- Length of ICU- stay and hospital-stay [ Time Frame: 12 months ]Length of ICU- stay and hospital-stay
- Evolution of the SOFA score between day 1 and day 28 or discharge-day from ICU as appropriate (in case of death before Day 28, the last SOFA score collected will be 24 points) [ Time Frame: 28 days ]
The Sequential Organ Failure Assessment (SOFA) score is calculated with the combination of 6 scores:
- respiratory score with the parameter PaO2/ FiO2
- neurological score with Mean arterial pressure parameter
- hepatic score with bilirubin parameter
- coagulation score with measure of platelets
- renal score with creatinine parameter
The total score will range to 0 at 24; 0 being the better outcome and 24 the worse.
- Variation of global extent of HRCT infiltrates between initial HRCT and Day 90 according to AKIRA et al [ Time Frame: 90 days ]Variation of global extent of HRCT infiltrates
- Changes in lung injury biomarkers in plasma (KL-6, SP-D) between day 1 and day 90 [ Time Frame: 90 days ]Changes in lung injury biomarkers in plasma
- Changes in circulating autoantibodies levels (anti-periplakin, anti-HSP70 and anti-vimentin antibodies) between day 1 and day 90 [ Time Frame: 90 days ]Changes in circulating autoantibodies levels
- Changes in the proportion of blood fibrocytes between day 1 and day 90 [ Time Frame: 90 days ]Changes in the proportion of blood fibrocytes between day 1 and day 90
- Proportion of patients with at least one episode of any healthcare-associated infection between inclusion and day 28 [ Time Frame: 28 days ]Proportion of patients with at least one episode of any healthcare-associated infection
- Proportion of catheter-linked complications between inclusion and day 16 [ Time Frame: 16 days ]Proportion of catheter-linked complications between inclusion and day 16
- Number of blood units transfused between inclusion and day 28 [ Time Frame: 28 days ]Number of blood units transfused between inclusion and day 28
- Proportion of major bleeding according to the International Society On Thrombosis and Haemostasis [ Time Frame: 28 days ]Proportion of major bleeding
- Proportion of patients with occurrence of an acute renal failure at day 28, according to the KDIGO guidelines [ Time Frame: 28 days ]Proportion of patients with occurrence of an acute renal failure
- Proportion of patients with anaphylactic reaction at day 28 [ Time Frame: 28 days ]Proportion of patients with anaphylactic reaction

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patient ≥ 18 years of age
- Admitted to ICU in the last 72 h
- Definite or probable IPF diagnosis defined on 2018 ATS/ERS/JRS/ALAT guidelines or a possible usual interstitial pneumonia pattern on HRCT without etiology.
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Definite AE-IPF according to the 2018 revised criteria :
- Previous or concurrent diagnosis of idiopathic pulmonary fibrosis (if the diagnosis of IPF is not previously established, this criterion can be met by the presence of radiologic and or histopathologic changes consistent with usual interstitial pneumonia (UIP) pattern on the current evaluation);
- Acute worsening or development of dyspnea typically of less than one-month duration;
- Computed tomography with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with a UIP pattern (if no previous computed tomography is available, the qualifier "new" can be dropped);
- Deterioration not fully explained by cardiac failure or fluid overload.
- PaO2/FiO2 ratio < 200 measured on FiO2 1
Exclusion Criteria:
- Known hypersensitivity intravenous immunoglobulins or rituximab
- Severe heart failure
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Active and uncontrolled bacterial fungal or parasitic infection ruled out by at least one of these two conditions
- Procalcitonin value at inclusion < 0.25 ng/mL OR
- Adapted antimicrobial therapy for at least 48 hours at inclusion
- Positive multiplex PCR for Influenzae A and B, or VRS
- Deep Veinous Thrombosis or Pulmonary embolism in the last six months
- Prior exposures to human-murine chimeric antibodies
- Ongoing treatment with a cellular immunosuppressant (e.g., cyclophosphamide, methotrexate, mycophenolate, azathioprine, calcineurin inhibitors, etc.)
- Subject treated with more than 2 boluses of methylprednisolone (total dose > 500mg of methylprednisolone) or one dose > 10mg/kg in the last 72 hours
- Uncorrectable coagulopathies or thrombocytopenia < 30000/mm3
- Active cancer (other than basal cell carcinoma of the skin)
- Other source of immunosuppression (i.e. HIV infection, solid organ transplant, lymphoma or leukemia)
- Pregnancy
- Patient listed for lung transplantation
- Patient on ECMO
- Patient with a do-not-intubate order at inclusion
- Concurrent participation in other experimental trials
- Not Affiliation to the French social security
- Not Written informed consent from the patient or a legal representative if appropriate
- Hypersensitivity to corticosteroids, cotrimoxazole / atovaquone
- Patients with severe renal insufficiency (creatine clearance <15ml / min)

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03584802
Contact: Bruno CRESTANI, Professor | 00 33 (1) 40 25 86 86 or 00 33 | bruno.crestani@aphp.fr | |
Contact: Mathilde NEUVILLE, Doctor | 00 33 (1) 40 25 77 98 | mathilde.neuville@aphp.fr |
France | |
Hôpital Bichat Claude Bernard | Recruiting |
Paris, France, 75018 | |
Contact: Bruno BC CRESTANI, Professor bruno.crestani@aphp.fr | |
Contact: Mathilde MN NEUVILLE, Doctor m.neuville@hopital-foch.com |
Principal Investigator: | Bruno CRESTANI, Professor | Assistance Publique - Hôpitaux de Paris |
Responsible Party: | Assistance Publique - Hôpitaux de Paris |
ClinicalTrials.gov Identifier: | NCT03584802 |
Other Study ID Numbers: |
P160915J |
First Posted: | July 12, 2018 Key Record Dates |
Last Update Posted: | June 11, 2020 |
Last Verified: | June 2020 |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
severe acute exacerbation of idiopathic pulmonary fibrosis |
Pulmonary Fibrosis Idiopathic Pulmonary Fibrosis Fibrosis Pathologic Processes |
Lung Diseases Respiratory Tract Diseases Idiopathic Interstitial Pneumonias Lung Diseases, Interstitial |