Idiopathic Pulmonary Fibrosis
Conditions
Brief summary
This randomized controlled trial evaluates the therapeutic role of azithromycin in acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF). Baseline severity classification and stratification were performed using the SCALE-IPF framework (Severity Classification and Lung Evaluation for Prognosis in IPF; locked April 2023) to ensure balanced disease severity across randomized arms. End-of-study analyses included descriptive and stratified phenotyping using the Idiopathic Pulmonary Fibrosis Phenotypes Identification Model (IPIM); locked April 2023). Following a protocol amendment approved in September 2025, the study expanded into a multi-arm therapeutic platform evaluating both azithromycin timing strategies and combination antifibrotic-immunomodulatory therapy in idiopathic pulmonary fibrosis. Additional treatment arms involving pirfenidone with or without azithromycin were incorporated without altering the original randomized comparisons or baseline study framework. Both frameworks were developed within the Assiut University IPF Research Program (2022-2026), a coordinated institutional effort investigating clinical, prognostic, and therapeutic dimensions of IPF. Neither framework altered randomization procedures, treatment allocation, or study endpoints; they were applied to improve standardization, reproducibility, and interpretability of results.
Detailed description
This randomized, open-label controlled trial forms part of the Assiut University IPF Research Program (2022-2026). An initial target of 130 patients with clinically mild or early-moderate acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) was specified for enrollment and randomized to receive standard therapy with or without azithromycin. SCALE-IPF (Severity Classification and Lung Evaluation for Prognosis in IPF; locked April 2023, archived November 2025, digital object identifier \[DOI\] 10.5281/zenodo.17575973) served as the prespecified baseline severity classification and stratification framework. IPIM (Idiopathic Pulmonary Fibrosis Phenotypes Identification Model; locked April 2023, archived November 2025, DOI 10.5281/zenodo.17576160) was applied as a predefined phenotypic framework integrating clinical, functional, and radiological domains. Severity and phenotypic frameworks were used exclusively to define eligibility and baseline characterization. They did not influence randomization procedures, treatment allocation, trial conduct, or study endpoints, and were applied to support reproducibility and structured interpretation of therapeutic effects across severity and phenotypic spectra. Protocol Amendment (September 2025) - Platform Expansion: To reflect the ongoing institutional clinical ecosystem, the trial was updated via a protocol amendment approved in September 2025 into a multi-arm single-center therapeutic platform. In addition to the original acute exacerbation cohort, the platform expanded to evaluate combination antifibrotic and immunomodulatory therapy targeting the inflammatory phenotype. Trial enrollment was concurrently expanded to target 250 patients per group. Two additional arms were integrated: Group C (Pirfenidone alone) and Group D (Pirfenidone plus Azithromycin). This expansion allows for two distinct, prespecified therapeutic contrasts from the same institutional infrastructure: an early versus delayed azithromycin intervention (Groups A/B), and a pirfenidone combination therapy concept (Groups C/D). The platform expansion does not alter the original randomized comparisons, original enrollment chronology, or original study endpoints. SCALE-IPF and IPIM frameworks continue to be utilized for baseline stratification and descriptive phenotyping across all expanded platform arms.
Interventions
DRUGAzithromycin
A single daily oral dose of azithromycin 500 mg for five days during acute exacerbation, followed by azithromycin 500 mg orally three times weekly as maintenance therapy during longitudinal follow-up according to tolerability and standard clinical safety monitoring.
DRUGMethylprednisolone
methylprednisolone 500 mg single intra-venous daily dose for three days
DRUGPirfenidone
Pirfenidone will be administered according to the standard full-dose protocol as 801 mg orally three times daily, equivalent to a total daily dose of 2403 mg/day, administered as three 267 mg tablets/capsules three times daily according to tolerability and standard clinical safety monitoring.
Sponsors
Assiut University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Baseline disease severity classified as mild or early-moderate according to the SCALE-IPF (locked April 2023) threshold ≤ 13 points. * Participation within the Assiut University IPF Research Program (2022-2026). * Additional longitudinal therapeutic platform arms involving pirfenidone with or without azithromycin may include clinically stable idiopathic pulmonary fibrosis patients according to protocol-amended eligibility criteria approved in September 2025.
Exclusion criteria
* Age: less than 18 years. * Patients with any severity other than mild or early-moderate acute exacerbation of IPF according to SCALE-IPF (locked April 2023). * Patients with multislice computed tomography with a radiological pattern rather than usual interstitial pneumonitis (UIP). * Unstable patients need mechanical ventilation or Respiratory Intensive Care Unit admission. * Patients with end-organ failure. * Patients with known hypersensitivity or contraindication to pirfenidone or azithromycin, significant hepatic impairment, severe drug intolerance, or other contraindications to study medications according to standard clinical judgment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hospital stay | 5-10 Days ( Days of Hospital admission until improvement and discharge) | the main aim of the study to assess the hospital stay expressed in days in the Add-on Azithromycin 500 mg single oral daily dose in comparison to the conventional therapy group only |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival across SCALE-IPF strata | Baseline to 12 months post-randomization. | Compare event-free survival (freedom from recurrent AE, hospitalization, or death) between azithromycin and control groups across SCALE-defined severity categories. |
| Change in clinical outcome measures stratified by SCALE-IPF severity | From randomization (Day 1) to Month 3 post-enrollment. | Evaluate the treatment response and short-term progression of AE-IPF patients across baseline severity strata as defined by the SCALE-IPF classification (locked April 2023). Outcomes include improvement in oxygenation, radiological resolution, and need for hospitalization. This will assess whether baseline SCALE-IPF strata correlate with therapeutic response and clinical stability. |
| Association between SCALE-IPF severity and one-year mortality | Baseline to 12 months post-randomization. | Determine whether baseline SCALE-IPF severity independently predicts 12-month all-cause mortality following acute exacerbation in both treatment arms. This analysis provides validation of the SCALE-IPF prognostic gradient within a randomized framework. |
| Correlation between azithromycin response and IPIM phenotypic clusters | Baseline to 12 months post-randomization. | Analysis comparing treatment outcomes across IPIM-defined phenotypic clusters |
Countries
Egypt
Contacts
CONTACTahmad M shaddad, MD
PRINCIPAL_INVESTIGATORahmad M shaddad
Assiut university-Faculty of Medicine
Outcome results
None listed