Role of Add-on Azithromycin in the Management of Patients With Acute Exacerbation of Idiopathic Pulmonary Fibrosis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 1,000
- 试验地点
- 2
- 主要终点
- Hospital stay
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Pirfenidone Plus Azithromycin Therapy
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.
干预措施: Azithromycin (Drug)
Pirfenidone Plus Azithromycin Therapy
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.
干预措施: Pirfenidone (Drug)
Pirfenidone Therapy
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.
干预措施: Pirfenidone (Drug)
Conventional therapy group
Patients will receive conventional treatment for acute exacerbation of IPF, including pulse corticosteroid therapy and supportive treatment, and oxygen therapy.
干预措施: Methylprednisolone (Drug)
Add-on Azithromycin
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.
干预措施: Azithromycin (Drug)
Add-on Azithromycin
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.
干预措施: Methylprednisolone (Drug)
结局指标
主要结局
Hospital stay
时间窗: 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
次要结局
- 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.)
研究者
Ahmad Shaddad
Lecturer of pulmonary medicine Assuit university
Assiut University