IVIG for sudden severe flare-ups of idiopathic pulmonary fibrosis

A Prospective, Multicenter, Randomized, Open-Label Clinical Trial Evaluating the Efficacy of Intravenous Immunoglobulin in Patients Hospitalized for Acute Exacerbations of Idiopathic Pulmonary Fibrosis.

This trial will try adding intravenous immunoglobulin (IVIG) to standard hospital care to see if it helps people hospitalized with sudden, severe worsening of idiopathic pulmonary fibrosis.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 196 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University General Hospital of Patras (Academic / other)
• Drugs / interventions: cyclophosphamide, prednisone
• Locations: 1 site (Pátrai)
• Trial ID: NCT07299695 on ClinicalTrials.gov

What this trial studies

This is a prospective, randomized, phase 3 study that will assign adults hospitalized with definite or suspected acute exacerbations of IPF to receive IVIG plus usual care or usual care alone. IVIG will be given as an adjunct to standard management, which typically includes pulse corticosteroids, broad-spectrum antibiotics, prophylactic anticoagulation, and oxygen. The trial is multicenter in design and focuses on clinically relevant outcomes such as survival and gas exchange during the acute hospitalization. Enrollment targets adults meeting international criteria for AE-IPF.

Who should consider this trial

Good fit: Adults (≥18 years) with a confirmed diagnosis of IPF who are hospitalized with a definite or suspected acute exacerbation by international criteria are the ideal candidates.

Not a fit: Patients who are not hospitalized for an acute exacerbation, whose respiratory decline is explained by cardiac failure or fluid overload, or who have contraindications to IVIG may not receive benefit from this approach.

Why it matters

Potential benefit: If successful, adding IVIG could reduce mortality and improve breathing and gas exchange during acute IPF exacerbations.

How similar studies have performed: Small retrospective reports and clinical experience in other rapidly progressive interstitial lung diseases suggest possible benefit from IVIG, but randomized phase 3 evidence is currently lacking.

Eligibility criteria

Inclusion Criteria:

1. Patients ≥ 18 years of age
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:

1. Patients with acute worsening due to uncontrolled heart failure or pulmonary embolism.
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.

Where this trial is running

Pátrai

• Department of Respiratory Medicine, University Hospital of Patras — Pátrai, Greece (Recruiting)

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