Intravenous Immunoglobulin for the Treatment of Acute Exacerbations of Idiopathic Pulmonary Fibrosis
NCT ID: NCT07299695
Last Updated: 2025-12-23
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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NOT_YET_RECRUITING
PHASE3
196 participants
INTERVENTIONAL
2025-12-31
2028-12-31
Brief Summary
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Detailed Description
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This prospective, multicenter, randomized study aims to address this critical unmet need by evaluating the efficacy of IVIG in patients with AE-IPF.
Aberrant inflammation and dysregulated immune responses are believed to play a key role in the pathogenesis of AE-IPF. Patients with IPF often display impaired cellular and humoral immunity, further supporting the investigation of immunomodulatory therapies. Intravenous immunoglobulin (IVIG), which has established anti-inflammatory and immunomodulatory effects, is used in other rapidly progressive interstitial lung diseases and in various immune-mediated conditions. Preliminary retrospective data from investigators' center suggest that IVIG may improve gas exchange and survival in patients hospitalized with acute exacerbations of fibrotic interstitial lung disease, including IPF.
Investigators hypothesize that the addition of IVIG to usual treatment may improve clinically relevant outcomes during AE-IPF. In this study, IVIG will be administered as an adjunct to usual care. Usual care will include pulse corticosteroids, broad-spectrum antibiotics, prophylactic anticoagulation, and oxygen therapy. Although the effectiveness of corticosteroids in AE-IPF remains uncertain and is supported only by low-quality evidence, their use is endorsed by current treatment guidelines and remains widespread in clinical practice. In addition, corticosteroids are being evaluated in ongoing trials (e.g., EXAFIP2, NCT05674994). Considering the complex, multi-pathway biology of AE-IPF and the documented synergistic effects of IVIG and corticosteroids in other immune-mediated conditions (such as Kawasaki disease, idiopathic thrombocytopenic purpura, and toxic epidermal necrolysis/Stevens-Johnson syndrome), corticosteroids will be administered to both study arms to avoid withholding a potentially beneficial therapy.
The primary objective of this clinical trial is to evaluate whether IVIG, when added to usual care, improves outcomes compared to usual care alone in patients hospitalized with AE-IPF. The primary endpoint is a composite of all-cause in-hospital mortality or the need for endotracheal intubation. This composite measure was selected because AE-IPF is a rapidly progressive and life-threatening event, and these outcomes represent the most objective, clinically meaningful indicators of deterioration. The use of this endpoint enables a comprehensive assessment of treatment efficacy by capturing both fatal and near-fatal clinical events.
Investigators anticipate that the findings of this study will generate important evidence regarding the potential role of IVIG in the management of AE-IPF and may contribute to future treatment recommendations for this highly lethal condition.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Usual treatment
Usual treatment will consist of broad-spectrum antibiotics, pulse methylprednisolone, prophylactic anticoagulation, and oxygen therapy with high-flow nasal cannula and will be provided to all participants, in both treatment arms.
Usual treatment
1. Corticosteroids:
A pulse regimen of IV methylprednisolone at 250 mg daily (days 1 to 3), with no additional corticosteroids thereafter.
2. Antibiotics:
Empirical broad-spectrum antibiotics starting from the first 24 hours of hospitalization - respiratory quinolone and/or an antipseudomonal penicillin. Duration or escalation of antibiotics may be adjusted based on available antibiograms or treating physician's clinical judgment.
3. Anticoagulation:
Prophylactic-dose anticoagulation - low molecular weight heparin or fondaparinux - throughout hospitalization. Patients with an established indication for therapeutic anticoagulation will be maintained on their therapeutic regimen.
4. Antifibrotic therapy:
Antifibrotics (nintedanib, pirfenidone, or nerandomilast) will be continued during hospitalization if already prescribed and not contraindicated. No new antifibrotic treatment will be initiated during the study period.
Intravenous immunoglobulin plus Usual treatment
Intravenous immunoglobulin will be administered along with usual treatment, as described.
Intravenous immunoglobulin (IVIG)
Total dose of 1 g/kg, divided over three consecutive days. The infusion will start at a rate of 0.5 mg/kg/hour for the first 15 minutes and, if no adverse reaction occurs, the rate will then be gradually increased step-wise as tolerated. Premedication with acetaminophen and levocetirizine.
Usual treatment will be co-administered, as described.
Interventions
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Intravenous immunoglobulin (IVIG)
Total dose of 1 g/kg, divided over three consecutive days. The infusion will start at a rate of 0.5 mg/kg/hour for the first 15 minutes and, if no adverse reaction occurs, the rate will then be gradually increased step-wise as tolerated. Premedication with acetaminophen and levocetirizine.
Usual treatment will be co-administered, as described.
Usual treatment
1. Corticosteroids:
A pulse regimen of IV methylprednisolone at 250 mg daily (days 1 to 3), with no additional corticosteroids thereafter.
2. Antibiotics:
Empirical broad-spectrum antibiotics starting from the first 24 hours of hospitalization - respiratory quinolone and/or an antipseudomonal penicillin. Duration or escalation of antibiotics may be adjusted based on available antibiograms or treating physician's clinical judgment.
3. Anticoagulation:
Prophylactic-dose anticoagulation - low molecular weight heparin or fondaparinux - throughout hospitalization. Patients with an established indication for therapeutic anticoagulation will be maintained on their therapeutic regimen.
4. Antifibrotic therapy:
Antifibrotics (nintedanib, pirfenidone, or nerandomilast) will be continued during hospitalization if already prescribed and not contraindicated. No new antifibrotic treatment will be initiated during the study period.
Eligibility Criteria
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Inclusion Criteria
2. Patients with IPF diagnosis that fulfils ATS/ERS Consensus Criteria.
3. Patients hospitalised with a definite or suspected AE-IPF diagnosis, as defined by the international working group criteria and as ascertained by the responsible Primary Investigator.
The criteria of IPF-AE are as follows:
* Previous or concurrent diagnosis of IPF
* Acute worsening or development of dyspnoea typically \< 1 month duration
* Computed tomography with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with usual interstitial pneumonia pattern
* Deterioration not fully explained by cardiac failure or fluid overload Patients who fail to meet all 4 criteria due to missing computed tomography should be considered as having "suspected Acute Exacerbation".
A) 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 pattern on the current evaluation.
B) If no previous computed tomography is available, the qualifier "new" can be dropped from the third AE-IPF criterion.
4. Patient able to understand and sign a written informed consent form. In case of incapacity of the patient, the written informed consent form will be signed by the patients' legally authorized representative.
Exclusion Criteria
2. Patients with known hypersensitivity to corticosteroids, IVIG or any component of the study treatment.
3. Patients with known IgA deficiency (IgA level \<7 mg/dL)- to preclude IVIG reactions.
4. Patients without a definite diagnosis of IPF or AE-IPF based on clinical, radiological, laboratory evaluation, and multidisciplinary discussion.
5. Patients with active malignancy or currently receiving cancer treatment, except for basal cell or squamous cell skin cancer or low-risk prostate cancer (T1 or T2a stage with PSA \<10 ng/dL). These criteria are aligned with current guidelines.
6. Patients that have received treatment for \>14 days within the preceding month with \>20mg daily prednisone (or equivalent) or any treatment during the last month with immunosuppressants (e.g., cyclophosphamide, mycophenolate etc.) according to already published therapeutic protocols or \> 1 mg/kg/d from more than 7 days in the last 15 days.
7. Patients participating to another interventional clinical trial.
8. Patients with documented pregnancy or lactation.
9. Patients under tutorship or curatorship.
10. Patients deprived of liberty or under court protection.
11. Patients who refuse to participate or decline to provide written informed consent.
18 Years
ALL
No
Sponsors
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Argyrios Tzouvelekis
OTHER
Responsible Party
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Argyrios Tzouvelekis
Professor of Internal and Respiratory Medicine, Head Department of Respiratory Medicine University of Patras, Greece - Associate Professor Adjunct, PCCSM, Yale School of Medicine, USA
Other Identifiers
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AT011225
Identifier Type: -
Identifier Source: org_study_id