Idiopathic Pulmonary FibrosisNCT05842681
Azithromycin in the Management of Patients With Acute Exacerbation of Idiopathic Pulmonary Fibrosis
A study testing Azithromycin, Methylprednisolone and Pirfenidone in people with Idiopathic Pulmonary Fibrosis, run by Assiut University at 2 sites in Egypt.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Idiopathic Pulmonary Fibrosis
- What is being tested?
- Azithromycin, Methylprednisolone and Pirfenidone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,000 participants
- Where
- 2 sitesEgypt
- Study dates
- 1 Jun 2023to 28 Feb 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Egypt2 sites, 1 recruiting
- Recruiting
Assiut university-Faculty of Medicine
Asyut, 71515
ahmad shaddad, MD, 01111171930, shaddad_ahmad@yahoo.com
- Active, not recruiting
Faculty of Medicine Assuit University
Asyut
About this study
Official title: Role of Add-on Azithromycin in the Management of Patients With Acute Exacerbation of Idiopathic Pulmonary Fibrosis
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.
Read the 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.
- Conditions
- Idiopathic Pulmonary Fibrosis
- Being tested
- Azithromycin, Methylprednisolone, Pirfenidone
- Medical subject headings
- Idiopathic Pulmonary Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzithromycinDrug
Also called azithromycin 500 mg oral tablet
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 called methylprednisolone 500 mg
methylprednisolone 500 mg single intra-venous daily dose for three days
PirfenidoneDrug
Also called Pirfenidone 267 mg oral tablet/capsule
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Azithromycin; Drug: Pirfenidone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 5-10 Days ( Days of Hospital admission until improvement and discharge)
Secondary outcomes (4)
Change in clinical outcome measures stratified by SCALE-IPF severity
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.
Measured: From randomization (Day 1) to Month 3 post-enrollment.
Association between SCALE-IPF severity and one-year mortality
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.
Measured: Baseline to 12 months post-randomization.
Correlation between azithromycin response and IPIM phenotypic clusters
Analysis comparing treatment outcomes across IPIM-defined phenotypic clusters
Measured: Baseline to 12 months post-randomization.
Event-free survival across SCALE-IPF strata
Compare event-free survival (freedom from recurrent AE, hospitalization, or death) between azithromycin and control groups across SCALE-defined severity categories.
Measured: Baseline to 12 months post-randomization.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2023
- Study start1 Jun 2023
- Primary completion1 Jan 2027 (estimated)
- Study completion28 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Idiopathic Pulmonary FibrosisStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized controlled trial
- Masking
- None (open label)
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ahmad Shaddad, Assiut University
- Investigators
- ahmad M shaddad, Principal investigator, Assiut university-Faculty of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05842681
- Sponsor's protocol ID
- 2516771716
- Status last verified
- May 2026
- First submitted
- 23 Apr 2023
- Last updated
- 13 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Add-on Azithromycin in the Management of Patients With Acute Exacerbation of Idiopathic Pulmonary Fibrosis
- ClinicalTrials.gov ID
- NCT05842681
- Acronym / sponsor ID
- 2516771716
- Conditions
- Idiopathic Pulmonary Fibrosis
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Jun 2023 (actual)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 28 Feb 2027 (estimated)
- First posted
- 6 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| Conventional therapy group | Active comparator | Drug: MethylprednisolonePatients will receive conventional treatment for acute exacerbation of IPF, including pulse corticosteroid therapy and supportive treatment, and oxygen therapy. |
| Add-on Azithromycin | Experimental | Drug: Azithromycin, Drug: MethylprednisolonePatients 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. |
| Pirfenidone Therapy | Active comparator | Drug: PirfenidonePirfenidone 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. |
| Pirfenidone Plus Azithromycin Therapy | Experimental | Drug: Azithromycin, Drug: PirfenidonePatients 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzithromycinAlso: azithromycin 500 mg oral tabletA 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. | Drug | Add-on Azithromycin, Pirfenidone Plus Azithromycin Therapy |
| MethylprednisoloneAlso: methylprednisolone 500 mgmethylprednisolone 500 mg single intra-venous daily dose for three days | Drug | Add-on Azithromycin, Conventional therapy group |
| PirfenidoneAlso: Pirfenidone 267 mg oral tablet/capsulePirfenidone 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. | Drug | Pirfenidone Plus Azithromycin Therapy, Pirfenidone Therapy |
Primary outcome
Hospital stay
Time frame: 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
4 secondary outcomes
Change in clinical outcome measures stratified by SCALE-IPF severity
Time frame: From randomization (Day 1) to Month 3 post-enrollment.
Association between SCALE-IPF severity and one-year mortality
Time frame: Baseline to 12 months post-randomization.
Correlation between azithromycin response and IPIM phenotypic clusters
Time frame: Baseline to 12 months post-randomization.
Event-free survival across SCALE-IPF strata
Time frame: Baseline to 12 months post-randomization.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
ahmad M shaddad principal investigator
Assiut university-Faculty of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Azithromycin, Methylprednisolone and Pirfenidone in people with Idiopathic Pulmonary Fibrosis, run by Assiut University at 2 sites in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact ahmad M shaddad, MD (01111171930, shaddad_ahmad@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hospital stay (time frame: 5-10 Days ( Days of Hospital admission until improvement and discharge)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2026.