Azithromycin in the Management of Patients With Acute Exacerbation of Idiopathic Pulmonary Fibrosis

NCT05842681 | Recruiting DMC

• 1 other identifier: 2516771716
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 2

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.

Conditions

Idiopathic Pulmonary Fibrosis

Outcome Measures

Primary Outcomes (1)

• Hospital stay

  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

  5-10 Days ( Days of Hospital admission until improvement and discharge)

Secondary Outcomes (4)

• Change in clinical outcome measures stratified by SCALE-IPF severity

  From randomization (Day 1) to Month 3 post-enrollment.

• Association between SCALE-IPF severity and one-year mortality

  Baseline to 12 months post-randomization.

• Correlation between azithromycin response and IPIM phenotypic clusters

  Baseline to 12 months post-randomization.

• Event-free survival across SCALE-IPF strata

  Baseline to 12 months post-randomization.

Other Outcomes (22)

• Analytical validation of SCALE-IPF and IPIM within the randomized AE-IPF cohort

  Baseline to 12 months post-randomization.

• Exacerbation frequency in the pirfenidone combination therapy domain

  Baseline to Month 12 post-randomization.

• Forced vital capacity decline in the pirfenidone combination therapy domain

  Baseline to Month 12 post-randomization.

Study Arms (4)

Conventional therapy group

ACTIVE COMPARATOR

Patients will receive conventional treatment for acute exacerbation of IPF, including pulse corticosteroid therapy and supportive treatment, and oxygen therapy.

Drug: Methylprednisolone

Add-on Azithromycin

EXPERIMENTAL

Patients will receive conventional therapy and Add-on Azithromycin 500 mg single daily dose for five days then Patients will receive conventional treatment and early adjunctive azithromycin according to the study treatment protocol. Azithromycin will be administered as a 500 mg oral dose three times weekly during longitudinal follow-up according to tolerability and standard clinical safety monitoring. This arm represents the early inflammatory intervention strategy targeting inflammatory disease behavior in idiopathic pulmonary fibrosis.

Drug: Azithromycin; Drug: Methylprednisolone

Pirfenidone Therapy

ACTIVE COMPARATOR

Pirfenidone will be administered according to the standard full-dose protocol as 801 mg orally three times daily, corresponding to a total daily dose of 2403 mg/day. This regimen is equivalent to nine 267 mg tablets/capsules per day, given as three tablets/capsules three times daily, according to tolerability and standard safety monitoring.

Drug: Pirfenidone

Pirfenidone Plus Azithromycin Therapy

EXPERIMENTAL

Patients will receive pirfenidone therapy according to the standard full-dose protocol: 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, combined with adjunctive azithromycin administered as a 500 mg oral dose three times weekly according to the study treatment protocol and standard safety monitoring.

Drug: Azithromycin; Drug: Pirfenidone

Interventions

Azithromycin DRUG

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.

Also known as: azithromycin 500 mg oral tablet

Add-on Azithromycin; Pirfenidone Plus Azithromycin Therapy

Methylprednisolone DRUG

methylprednisolone 500 mg single intra-venous daily dose for three days

Also known as: methylprednisolone 500 mg

Add-on Azithromycin; Conventional therapy group

Pirfenidone DRUG

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.

Also known as: Pirfenidone 267 mg oral tablet/capsule

Pirfenidone Plus Azithromycin Therapy; Pirfenidone Therapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assiut University: lead

Study Sites (2)

Assiut university-Faculty of Medicine

Asyut, 71515, Egypt

RECRUITING

Faculty of Medicine Assuit University

Asyut, Egypt

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

Azithromycin; Methylprednisolone; pirfenidone; Tablets; Capsules

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Study Officials

• ahmad M shaddad

  Assiut university-Faculty of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

ahmad M shaddad, MD

CONTACT

01111171930; shaddad_ahmad@yahoo.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of pulmonary medicine Assuit university

Model Details: Randomized controlled trial

Study Record Dates

• First Submitted: April 23, 2023
• First Posted: May 6, 2023
• Study Start: June 1, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): February 28, 2027
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

EG (2)