Intravenous Immunoglobulin for the Treatment of Acute Exacerbations of Idiopathic Pulmonary Fibrosis

NCT07299695 | Recruiting Phase 3

• 1 other identifier: AT011225
• Study Type: interventional
• Target: 196
• Locations: 1 country
• Sites: 1

Brief Summary

Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) are sudden and severe worsening episodes that can be life-threatening. Currently, no treatment has been proven to clearly improve outcomes during these events. Inflammation and immune system imbalance are thought to play an important role in causing AE-IPF. Early clinical experience suggests that intravenous immunoglobulin (IVIG) can be beneficial for patients suffering from AE-IPF. This clinical trial aims to determine whether adding IVIG to usual treatment can improve outcomes for patients hospitalized with AE-IPF.

Conditions

Acute Exacerbation of Idiopathic Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis

Keywords

Acute Exacerbations of Idiopathic Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Intravenous Immunoglobulin; Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Outcome Measures

Primary Outcomes (1)

• All-cause in-hospital mortality or intubation

  This outcome corresponds to the all-cause mortality or intubation rate throughout hospitalisation.

  From date of randomization until the outcome mesure - the date of death from any cause or the date of endotracheal intubation, whichever comes first - assessed up to 4 weeks during hospitalisation.

Secondary Outcomes (6)

• All-cause 30-day mortality

  30 days from hospital admission

• All-cause 90-day mortality

  90 days from hospital admission

• Hospital readmissions

  180 days from hospital admission

• New acute exacerbation IPF

  180 days from hospital admission

• Change in PaO₂/FiO₂ Ratio

  PaO₂/FiO₂ ratio will be assessed at the day of randomisation prior to therapeutic interventions (except oxygen therapy) and then at the day of hospital discharge - up to 4 weeks post randomisation.

Other Outcomes (2)

• Change in FVC

  90 days from hospital admission

• Change in DLCO

  90 days from hospital admission

Study Arms (2)

Usual treatment

ACTIVE COMPARATOR

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.

Drug: Usual treatment

Intravenous immunoglobulin plus Usual treatment

EXPERIMENTAL

Intravenous immunoglobulin will be administered along with usual treatment, as described.

Drug: Intravenous immunoglobulin (IVIG)

Interventions

Intravenous immunoglobulin (IVIG) DRUG

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.

Intravenous immunoglobulin plus Usual treatment

Usual treatment DRUG

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.

Usual treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥ 18 years of age
• Patients with IPF diagnosis that fulfils ATS/ERS Consensus Criteria.
• 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.
• 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.

You may not qualify if:

• Patients with acute worsening due to uncontrolled heart failure or pulmonary embolism.
• Patients with known hypersensitivity to corticosteroids, IVIG or any component of the study treatment.
• Patients with known IgA deficiency (IgA level \<7 mg/dL)- to preclude IVIG reactions.
• Patients without a definite diagnosis of IPF or AE-IPF based on clinical, radiological, laboratory evaluation, and multidisciplinary discussion.
• 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.
• 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.
• Patients participating to another interventional clinical trial.
• Patients with documented pregnancy or lactation.
• Patients under tutorship or curatorship.
• Patients deprived of liberty or under court protection.
• Patients who refuse to participate or decline to provide written informed consent.

Sponsors & Collaborators

• Argyrios Tzouvelekis: lead

Study Sites (1)

Department of Respiratory Medicine, University Hospital of Patras

Pátrai, 26504, Greece

RECRUITING

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

Immunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Internal and Respiratory Medicine, Head Department of Respiratory Medicine University of Patras, Greece - Associate Professor Adjunct, PCCSM, Yale School of Medicine, USA

Study Record Dates

• First Submitted: November 26, 2025
• First Posted: December 23, 2025
• Study Start: January 25, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

GR (1)