The DEBATE Study "DEvelopment of Endotype-based Biomarkers for the Monitoring of Greek pATiEnts With CRSwNP" (DEBATE)

Given the high variability in the inflammatory profiles of CRSwNP (Chronic rhinosinusitis with nasal polyps) patients that influence both disease phenotype and response to treatment, exploring further potential targets is crucial for advancing novel biologic treatment strategies. By indicating the efficacy of targeted therapy, as well as determining clinical features, endotyping of CRSwNP may offer a useful tool to better tailor treatment approaches in this heterogenous patient population. This study is the first national effort to collect data on inflammatory markers and burden of CRSwNP patients in Greece aiming at identifying disease endotypes based on patients' inflammatory profile.

Study Overview

• Status: Recruiting
• Conditions: CRSwNP or CRSsNP Patients
• Intervention / Treatment: Other: Not applicable - NIS study

Detailed Description

A participant may withdraw from the study at any time at the participant's own request for any reason (or without providing any reason) without any implication on participant's rights. Patients who discontinue should be asked about the reason(s) for their discontinuation. If the participant withdraws consent for disclosure of future information, AstraZeneca may retain and continue to use any data collected before such a withdrawal of consent

• Study Type: Observational
• Enrollment (Estimated): 230

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Greece
  • Alexandroupoli, Greece
    • Recruiting
    • Research Site
  • Athens, Greece
    • Not yet recruiting
    • Research Site
  • Heraklion, Greece
    • Not yet recruiting
    • Research Site
  • Thessaloniki, Greece
    • Not yet recruiting
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

CRSwNP patients who are scheduled to undergo first ESS (prospective patients) will be recruited from approximately 6 Ear-Nose-Throat (ENT) and 1 pulmonology clinics. Moreover, CRSwNP and CRSsNP patients who have already performed their first ESS in the period between 2012 and enrolment and have stored nasal tissue samples (retrospective patients) will be recruited from 1 ENT clinic.

Description

Inclusion Criteria:

• Age ≥ 18 years
• If CRSwNP group:

Physician-diagnosed severe, uncontrolled CRSwNP according to the EUFOREA/EPOS 2020 and ICAR-RS 2021 guidelines with:

• CRSwNP severity consistent with the need for surgery as defined by a total nasal polyp score (NPS) of ≥5 (≥2 for each nostril)
• Nasal Congestion Score (NCS) of ≥2
• Ongoing documented symptoms of CRSwNP for > 8 weeks before surgery

If CRSsNP group:

Diagnosis of CRSsNP according to the EUFOREA/EPOS 2020 and ICAR-RS 2021 guidelines

• Have performed in the period between 2012 and enrolment or are scheduled to perform endoscopic sinus surgery (ESS) for the first time at enrolment
• Have available nasal polyp tissue sample from the first endoscopic sinus surgery (ESS)
• Have provided signed and dated written informed consent
• If CRSwNP group:

Patients receiving any standard of care treatment for CRSwNP, provided the participant is stable on that treatment for ≥30 days

Exclusion Criteria:

• Patients with cystic fibrosis or immunodeficiency
• Presence of acute exacerbation of CRS symptoms within 2 weeks prior to surgery
• Use of systemic corticosteroids within 30 days prior to surgery, or antileukotrienes within 15 days prior to surgery, or biologic therapy prior to surgery
• Not adequate amount (<0.15g) or quality (e.g. storage temperature, contamination) of tissue sample for analyses
• Not available blood (serum) sample, only for patients scheduled to perform endoscopic sinus surgery (ESS) for the first time at the date of enrolment, for analyses.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Prospective (CRSwNP); CRSwNP patients who are scheduled to undergo first ESS (Endoscopic sinus surgery)	Other: Not applicable - NIS study; Not applicable - NIS study
Retrospective (CRSwNP); CRSwNP patients who have already performed their first ESS in the period between 2012 and enrolment and have stored nasal tissue samples	Other: Not applicable - NIS study; Not applicable - NIS study
Retrospective (CRSsNP); CRSsNP (Chronic rhinosinusitis without nasal polyps) patients who have already performed their first ESS in the period between 2012 and enrolment and have stored nasal tissue samples	Other: Not applicable - NIS study; Not applicable - NIS study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of nasal tissue-secreted cytokines/chemokines in patients with CRSwNP	Cytokine/chemokine analysis of the fresh extracted nasal tissue following first ESS will be performed by Luminex and ELISA analysis	At Visit 1 (day 1)
Characterization of nasal tissue immune cell populations in prospective patients with CRSwNP	Immunophenotypic analysis by spectral flow cytometry of all main immune cell types, as well as detailed characterization of all T cell subsets will be performed in the fresh samples.	At Visit 1 (day 1)
Characterization of eosinophil and neutrophil cell counts in patients with CRSwNP	Eosinophil and neutrophil cell counts will be recorded, as per the EPOS 2020, eosinophilia is defined as >10 eosinophils/hpf.	At Visit 1 (day 1)
Characterization of nasal histological alterations in retrospective patients with CRSwNP	Tissue morphology and potential tissue destruction and nasal epithelium remodeling by standard histology staining (e.g. hematoxylin and eosin, Periodic Acid-Schiff (PAS), and Sirius Red staining) will be assessed in stored nasal polyp tissue paraffin sections or paraffin blocks.	At Visit 1 (day 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1i. Description of demographics of CRSwNP patients before and during 24 months after first endoscopic sinus surgery (ESS)	Demographics at study entry/screening (age, sex, ethnicity, smoking status, cigarettes/day/year, alcohol status (units/week), body measurements (BMI kg/m2), employment status, educational level, residence area) will be recorded	Up to 24 ± 2 months (through study completion)
1i. Description of medical history of CRSwNP patients before and during 24 months after first endoscopic sinus surgery (ESS)	Patients' medical history, including the date of first and severe CRSwNP diagnosis, comorbidities, and disease management [use (yes/no) of saline, systemic/local glucocorticoids, biologics, antibiotics], will be reported at the time of enrolment and during 24 months after first ESS.	Up to 24 ± 2 months (through study completion)
1i. Description of first ESS characteristics in CRSwNP patients	Time to first ESS from CRSwNP diagnosis and from severe CRSwNP diagnosis will be assessed	At Visit 1 (day 1)
1ii. Assessment of 22-item Sinonasal Outcome Test (SNOT-22) score in CRSwNP patients	The 22-item Sinonasal Outcome Test (SNOT-22), which is a health-related quality of life (HRQoL) evaluation with each item scored on a Likert scale ranging from 0 "No problem" to 5 "Problem as bad as it can be".	Up to 24 ± 2 months (through study completion)
1ii. Assessment of The Nasal Polyposis Symptom Diary (NPSD) in CRSwNP patients	The Nasal Polyposis Symptom Diary (NPSD), which is a short patient-reported outcome (PRO) tool comprising 11 items (8 symptom-specific, 2 symptom-impact, and 1 optional medication-compliance). The Total Symptom Score (TSS) is a summary of the first 8 symptom-specific items, scored on a 4-point scale [0-none, 1-mild, 2-moderate, 3-severe], with a resulting score from 0 to 24	Up to 24 ± 2 months (through study completion)
1ii. Assessment of the Asthma Control Test (ACT) in CRSwNP patients (if comorbidity with asthma)	The Asthma Control Test (ACT), a patient-based tool for identifying patients with poorly controlled asthma that includes 5 items assessing the frequency of shortness of breath and general asthma symptoms, use of rescue medications, the effect of asthma on daily functioning, and overall self-assessment of asthma control. The ACT responses for each of the items are summed to yield a score ranging from 5 (poor control of asthma) to 25 (complete control of asthma), with higher scores reflecting greater asthma control.	Up to 24 ± 2 months (through study completion)
1iii. Assessment of Nasal Polyps Score (NPS) score in CRSwNP patients	NPS is a physician-reported tool that grades the extent/severity of nasal polyps based on evaluation by nasal endoscopy. Each nostril is scored on a scale of 0 - "No nasal polyps" to 4 - "Large nasal polyps causing complete obstruction of the inferior nasal cavity", with the total score being the sum of left and right nostril scores (range: 0-8).	Up to 6 months before Visit 1 (day 1) & at Visit 2 (24 ± 2 months)
1iii. Assessment of imaging results in CRSwNP patients	The Lund-Mackay (LM) CT score that evaluates sinus opacification on CT scans. This score ranges from 0 -"complete lucency of all sinuses" to 24 - "complete opacity of all sinuses"	Up to 6 months before Visit 1 (day 1) & at Visit 2 (24 ± 2 months)
2. Characterization of blood cytokines/chemokines in prospective patients with CRSwNP	Cytokine/chemokine analysis of blood samples following first ESS will be performed by Luminex and ELISA analysis	At Visit 1 (day 1)
2. Characterization of blood immune cell populations in prospective patients with CRSwNP	Immunophenotypic analysis by spectral flow cytometry of all main immune cell types, as well as detailed characterization of all T cell subsets will be performed in the fresh samples.	At Visit 1 (day 1)
2. Characterization of serum immunoglobulin levels in prospective patients with CRSwNP	Serum immunoglobulin levels [total IgE, specific IgE to staphylococcal enterotoxins (SE-IgE)]	At Visit 1 (day 1)
2. Characterization of WBC count in prospective patients with CRSwNP	Differential WBC count (incl. absolute count) will be recorded	At Visit 1 (day 1)
2. Characterization of RBC count in prospective patients with CRSwNP	RBC count will be recorded	At Visit 1 (day 1)
3. Association of time to CRSwNP recurrence and CRSwNP endotypes over 24 months following first ESS in CRSwNP patients	The number of CRSwNP recurrences along with the date(s) of recurrence(s) will be recorded in the eCRF by the investigator at 24 months following first ESS for CRSwNP patients (including retrospective CRSwNP patients, if data are available). The time to relapse during the 24-month follow-up will be also estimated.	Up to 24 ± 2 months (through study completion)
4. Differences in cytokine/chemokine levels between retrospective patients with CRSwNP and CRSsNP	Endotypes of CRSsNP patients who have performed first ESS in the period between 2012 and enrolment (retrospective patients) will be determined based on cytokine/chemokine analysis of frozen extracted nasal tissue from ESS, including Fractalkine, GM-CSF, IFNγ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, (p70), IL-13, IL-17A, IL-21, IL-23, ITAC, MIP-1α, MIP-1β, MIP-3α, TNF-α, TSLP, IL-9, IL-33, IL-17E/IL-25, TGFb1, IL-22	At Visit 1 (day 1)
4. Differences in eosinophil and neutrophil cell counts between retrospective patients with CRSwNP and CRSsNP	Eosinophil and neutrophil cell counts will be recorded. As per the EPOS 2020, eosinophilia is defined as >10 eosinophils/hpf	At Visit 1 (day 1)
4. Differences in nasal tissue alterations between retrospective patients with CRSwNP and CRSsNP	tissue morphology and potential nasal tissue destruction and remodeling by standard histology staining (e.g. Hematoxylin and eosin, Periodic acid-Schiff (PAS), and Sirius Red staining) will be assessed in stored nasal polyp tissue paraffin sections or paraffin blocks. Depending on the nature of tissue pathology, further immunohistochemical analysis will be performed with the use of specific antibodies, such as markers for epithelial barrier integrity (e.g. E-cadherin or Cytokeratin), tissue remodeling (e.g. MMP-9) or chronic damage monitored by fibrosis (e.g. α-SMA or collagen)	At Visit 1 (day 1)

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: May 18, 2026
• First Submitted That Met QC Criteria: June 17, 2026
• First Posted (Actual): June 23, 2026

Study Record Updates

• Last Update Posted (Actual): July 22, 2026
• Last Update Submitted That Met QC Criteria: July 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: CRSwNP; CRSsNP; endotypes; inflammatory pathways
• Other Study ID Numbers: D5242R00007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No