Chronic Rhinosinusitis with Nasal PolypsPhase 4NCT05598814
Mepolizumab to CRSwNP Through 12 Months - Randomised to FESS and Non-FESS Within the First 2 Weeks
A Phase 4 study testing Mepolizumab Injection and Functional Endoscopic Sinus Surgery (FESS). in people with Chronic Rhinosinusitis with Nasal Polyps and Asthma, run by Vibeke Backer at 1 site in Denmark.
Trial summary
This clinical trial will compare treatment in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma. The patients will be randomized to treatment with the biologic drug, Mepolizumab, or the biologic drug Mepolizumab combined with Functional Endoscopic Sinus Surgery (FESS). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Rhinosinusitis with Nasal Polyps, Asthma
- What is being tested?
- Mepolizumab Injection and Functional Endoscopic Sinus Surgery (FESS).
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Apr 2023to 31 Aug 2025
- Phase
- Phase 4
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients ≥ 18 years old at the time of signed informed consent (no upper limit)
- Patients who are referred to the outpatient clinic for the following reasons:
- Doctor's diagnosis of CRS
- NPS ≥ 2+2 out of a score of 8 (max)
- Severity measured as an SNOT22 score > 35
- One FESS surgery in general anaesthesia performed prior to inclusion (no time limitations)
Show all 9Show fewer
- No course of systemic steroids within the last 3 months, whereas a daily low dose is allowed
- Possible doctor's diagnosis of asthma
- Type 2 inflammation
Who cannot join
- Patients who, because of language barriers, are not able to understand written information and, thus, are not able to answer questionnaires
- Patients who currently receive biologics for any other disease
- Patients who have previously or currently received biologics for CRS or asthma
- Patients who are not able to give informed consent (i.e., patients who are permanently incapable)
- Patients who meet ≥1 of the following:
- Malignant lung disease
Show all 11Show fewer
- Cardiac disease of clinical importance
- Current pregnancy and breastfeeding, as well as planning to be pregnant in the near future
- Unwillingness to have FESS performed
- Patients needing FESS or systemic steroids (OCS) during the study period will be excluded after an unscheduled visit (last observation carried forward (LOCF))
- Patients who are not eligible because of the investigator's judgement
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Rigshospitalet, Department of Otorhinolaryngology, Head and Neck Surgery & Audiology
Copenhagen, 2100
About this study
Official title: Optimisation of Treatment in Patients with CRSwNP. an RCT of Mepolizumab and Surgical Treatment with FESS and Mepolizumab Versus Only Mepolizumab Over a 6- and 12-month Follow-up
This clinical trial will compare treatment in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma. The patients will be randomized to treatment with the biologic drug, Mepolizumab, or the biologic drug Mepolizumab combined with Functional Endoscopic Sinus Surgery (FESS).
The aim of this study is to evaluate the effect of combined treatment with biologic treatment and surgery vs. biologic treatment only.
Read more
The hypothesis is that surgical removal of polyps and inflamed tissue from the nasal sinuses will increase the effect of the biologic treatment, leading to a lower disease burden after 6 months of treatment, compared with biologic drugs only. Furthermore, combined biologics and surgery will keep a lower disease burden and better general health after 12 months of treatment than biologics alone.
Inclusion criteria:
- Patients ≥ 18 years old at the time of signed informed consent (no upper limit)
- Patients who are referred to the outpatient clinic for the following reasons:
- Doctor's diagnosis of CRS
- NPS ≥ 2+2 out of a score of 8 (max)
- Severity measured as an SNOT22 score > 35
- One FESS in general anaesthesia performed prior to inclusion (no time limitations)
- No course of systemic steroids within the last 3 months, whereas a daily low dose is allowed
- Possible doctor's diagnosis of asthma
- Type 2 inflammation
Exclusion criteria:
- Patients who, because of language barriers, are not able to understand written information and, thus, are not able to answer questionnaires
- Patients who currently receive biologics for any other disease
- Patients who have previously or currently received biologics for CRS or asthma
- Patients who are not able to give informed consent (i.e., patients who are permanently incapable)
- Patients who meet ≥1 of the following:
- Malignant lung disease
- Cardiac disease of clinical importance
- Current pregnancy and breastfeeding, as well as planning to be pregnant in the near future
- Unwillingness to have FESS performed
- Patients needing FESS or systemic steroids (OCS) during the study period will be excluded after an unscheduled visit (last observation carried forward (LOCF))
- Patients who are not eligible because of the investigator's judgement
The effect of the treatment will be evaluated with objective procedures and questionnaires related to CRSwNP and asthma after 3, 6 and 12 months.
- Conditions
- Chronic Rhinosinusitis with Nasal Polyps, Asthma
- Being tested
- Mepolizumab Injection, Functional Endoscopic Sinus Surgery (FESS).
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mepolizumab InjectionBiological
All patients in both the intervention group and the control group will be treated with Mepolizumab injections every month.
Functional Endoscopic Sinus Surgery (FESS).Procedure or surgery
The Functional Endoscopic Sinus Surgery will be performed 2 weeks after the first injection of Mepolizumab in the intervention group.
| Study group | Role | What they receive |
|---|---|---|
| Intervention group - FESS | Experimental | Biologic treatment with Mepolizumab and functional endoscopic sinus surgery (FESS). Receives: Biological: Mepolizumab Injection; Procedure: Functional Endoscopic Sinus Surgery (FESS). |
| Control group - No-FESS | Active comparator | Biologic treatment with Mepolizumab Receives: Biological: Mepolizumab Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in The Sino-Nasal Outcome Test 22 (SNOTT22) score
The success rate indicated by a significant change in health-related quality of life related to nasal symptoms measured with the questionnaire SNOT22. The outcomes to be evaluated are the differences in success rates between the two treatment arms Minimum score = 0 and maximum score = 110 with high scores indicating a large rhinosinusitis-related health burden.
Measured: 6 months
Secondary outcomes (23)
Change in Vo2max/kg(Cardiopulmonary exercise test )
Highest oxygen consumption measured on a stationary ergometer bike divided by body weight. MCID: 1 ml/min/kg
Measured: 6 and 12 motnhs folow-up
Change in Daily step count
Measured as an average daily step count over 7 days using a smartphone
Measured: 6 and 12 months follow up
Change in Activity level(questionnaire)
Patient's self-reported amount of exercise, measured using a questionnaire (customised AQUA)
Measured: 6 and 12 months follow up
Change in Nasal Polyp Score (NPS)
The NPS scale ranges from 0 (no polyp) to 4 (large polyps) for each nostril. The total score ranging from 0-8.
Measured: 3 and 6 months follow up
Change in Forced Expired Volume in the first second (FEV1)
Change in Forced Expired Volume in the first second (FEV1). The value is corrected for age, sex, height and weight.
Measured: 6 and 12 months follow up
Change in forced vital capacity (FVC)
The value is corrected for age, sex, height and weight.
Measured: 3, 6, and 12 months follow up
Change in Asthma Control Questionnaire (ACQ) score
Change in ACQ-score. Minimum score = 0 and maximum score = 6 with high scores indicating a large asthma-related health burden.
Measured: 3, 6, and 12 months follow up
Change in ratio between FEV1/FVC
FEV1 divided by FVC. A ratio <0.70 is considered as obstructive.
Measured: 3, 6, and 12 months follow up
Change in nitric oxide in exhaled air
Change in nitric oxide in exhaled air examined with Exhaled Nitric Oxide Test (FeNO). A value between 0-25 is normal. A value >25 indicates inflammation in the airways.
Measured: 6 and 12 months follow up
Change in middle ear pressure
Change in middle ear pressure examined with a tympanometry. A =normal, B= flat curve, fluid or perfusion, C1= negative pressure down to -150 dPa, C2 = negative pressure below -150 dPA.
Measured: 12 months
Change in olfactory function
Change in olfactory function measured with Sniffin' Sticks Identification Test 16.
Minimum score = 0. Maximum score = 16. A score between 0-8 indicates anosmia, a score between 8-11 indicates hyposmia, and a score >11 indicates normosmia.
Measured: 6 and 12 months follow up
Change in Functional Outcomes of Sleep Questionnaire (FOSQ) score
FOSQ-10 consists of 10 questions rated on a scale of 1 to 4 (1=extreme difficulty and 4=no difficulty).
Measured: 3, 6, and 12 months follow up
Change in Epworth Sleepiness score (ESS)
ESS consists of 8 questions rated on a scale of 0 to 3 (3=extreme difficulty and 0=no difficulty)
Measured: 3, 6, and 12 months follow up
Change in AHI/ODI
Measurement of objective sleep parameters (Apnea hypopnea index and Oxygen desaturation index)
Measured: 6, and 12 months follow up
Change in Blood Eosinophilic cell count
Blood Eosinophilic cell count from full blood cell count (109/mL).
Measured: 3, 6, and 12 months follow up.
Change in Polyp Eosinophilic cell count
Tissue eosinophilia, classified into four categories: none (0), mild (<10 hpf), moderate (10-100 hpf), and severe (>100 hpf).
Measured: 6 and 12 months follow up.
Change in Small airway dysfunction
Measured by the average flow from the point at which 25 percent of the FVC has been exhaled to the point at which 75 percent of the FVC has been exhaled(MFEF75/25) and Impulse oscillometry: Difference in R5Hz and R20Hz , AX and X5Hz.
Measured: 6 and 12 months follow up.
Change in Bronchial hyperresponsiveness
Assessed through methacholine and mannitol challenge tests. Methacholine inhalation ranged from 0 to 1440 µg, with a positive test defined as a ≥20% decrease in FEV1 (PD20). Mannitol inhalation ranged from 0 to 635 mg, with a positive test defined as a ≥15% decrease in FEV1 (PD15)
Measured: 6 and 12 months follow up
Change in eosinophilic cell count in sputum
Sputum induced through the inhalation of hypertonic saline at increasing concentrations (3%, 4%, and 5%). Percentual amount of Eosinophilic cells.
Measured: 6 and 12 months follow up
Change in NasalNO
A value greater then 255-300 is considered normal, whereas values less than 77 nl/min is abnormal.
Measured: 6 and 12 months follow up
Change in visual analogue scale (VAS)
Change in VAS related to nasal symptoms. Minimum score = 0 and maximum score = 10. High score indicates worse nasal symptoms
Measured: 3, 6, and 12 months follow up
Change in visual analogue scale (VAS)
Change in VAS related to asthma symptoms. Minimum score = 0 and maximum score = 100. High score indicates worse Asthma symptoms
Measured: 3, 6, and 12 months follow up
Change in visual analogue scale (VAS)
Change in VAS related to Smell. Minimum score = 0 and maximum score = 100. High score indicates worse Hyposmia Symptoms.
Measured: 3, 6 and 12 months follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2022
- Study start1 Apr 2023
- Primary completion31 Aug 2024
- Study completion31 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Rhinosinusitis with Nasal PolypsStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The study is a randomized clinical trial with two arms. Arm 1: Biologic treatment with Mepolizumab every month combined with Arm 2: Only biologic treatment with Mepolizumab every month combined with Functional Endoscopic Sinus Surgery (FESS) 2 weeks after the first injection of Mepolizumab.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vibeke Backer
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Vibeke Backer, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Vibeke B Backer, Professor, Study chair, Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05598814
- Sponsor's protocol ID
- 2022-ENT-FESS-nonFESS
- Status last verified
- Nov 2024
- First submitted
- 25 Oct 2022
- Last updated
- 30 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimisation of Treatment in Patients with CRSwNP. an RCT of Mepolizumab and Surgical Treatment with FESS and Mepolizumab Versus Only Mepolizumab Over a 6- and 12-month Follow-up
- ClinicalTrials.gov ID
- NCT05598814
- Acronym / sponsor ID
- 2022-ENT-FESS-nonFESS
- Conditions
- Chronic Rhinosinusitis with Nasal Polyps, Asthma
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- Vibeke BackerUniversity, hospital or other
- Study start
- 1 Apr 2023 (actual)
- Primary completion
- 31 Aug 2024 (actual)
- Study completion
- 31 Aug 2025 (estimated)
- First posted
- 28 Oct 2022 (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 clinical trial will compare treatment in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma. The patients will be randomized to treatment with the biologic drug, Mepolizumab, or the biologic drug Mepolizumab combined with Functional Endoscopic Sinus Surgery (FESS).
The aim of this study is to evaluate the effect of combined treatment with biologic treatment and surgery vs. biologic treatment only.
The hypothesis is that surgical removal of polyps and inflamed tissue from the nasal sinuses will increase the effect of the biologic treatment, leading to a lower disease burden after 6 months of treatment, compared with biologic drugs only. Furthermore, combined biologics and surgery will keep a lower disease burden and better general health after 12 months of treatment than biologics alone.
Inclusion criteria:
- Patients ≥ 18 years old at the time of signed informed consent (no upper limit)
- Patients who are referred to the outpatient clinic for the following reasons:
- Doctor's diagnosis of CRS
- NPS ≥ 2+2 out of a score of 8 (max)
- Severity measured as an SNOT22 score > 35
- One FESS in general anaesthesia performed prior to inclusion (no time limitations)
- No course of systemic steroids within the last 3 months, whereas a daily low dose is allowed
- Possible doctor's diagnosis of asthma
- Type 2 inflammation
Exclusion criteria:
- Patients who, because of language barriers, are not able to understand written information and, thus, are not able to answer questionnaires
- Patients who currently receive biologics for any other disease
- Patients who have previously or currently received biologics for CRS or asthma
- Patients who are not able to give informed consent (i.e., patients who are permanently incapable)
- Patients who meet ≥1 of the following:
- Malignant lung disease
- Cardiac disease of clinical importance
- Current pregnancy and breastfeeding, as well as planning to be pregnant in the near future
- Unwillingness to have FESS performed
- Patients needing FESS or systemic steroids (OCS) during the study period will be excluded after an unscheduled visit (last observation carried forward (LOCF))
- Patients who are not eligible because of the investigator's judgement
The effect of the treatment will be evaluated with objective procedures and questionnaires related to CRSwNP and asthma after 3, 6 and 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- The study is a randomized clinical trial with two arms. Arm 1: Biologic treatment with Mepolizumab every month combined with Arm 2: Only biologic treatment with Mepolizumab every month combined with Functional Endoscopic Sinus Surgery (FESS) 2 weeks after the first injection of Mepolizumab.
| Arm | Type | Receives |
|---|---|---|
| Intervention group - FESS | Experimental | Biological: Mepolizumab Injection, Procedure: Functional Endoscopic Sinus Surgery (FESS).Biologic treatment with Mepolizumab and functional endoscopic sinus surgery (FESS). |
| Control group - No-FESS | Active comparator | Biological: Mepolizumab InjectionBiologic treatment with Mepolizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients ≥ 18 years old at the time of signed informed consent (no upper limit)
- Patients who are referred to the outpatient clinic for the following reasons:
- NPS ≥ 2+2 out of a score of 8 (max)
- Severity measured as an SNOT22 score > 35
- One FESS surgery in general anaesthesia performed prior to inclusion (no time limitations)
Key exclusion criteria (11 listed)
- Patients who, because of language barriers, are not able to understand written information and, thus, are not able to answer questionnaires
- Patients who currently receive biologics for any other disease
- Patients who have previously or currently received biologics for CRS or asthma
- Patients who are not able to give informed consent (i.e., patients who are permanently incapable)
- Patients who meet ≥1 of the following:
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 |
|---|---|---|
| Mepolizumab InjectionAll patients in both the intervention group and the control group will be treated with Mepolizumab injections every month. | Biological | Control group - No-FESS, Intervention group - FESS |
| Functional Endoscopic Sinus Surgery (FESS).The Functional Endoscopic Sinus Surgery will be performed 2 weeks after the first injection of Mepolizumab in the intervention group. | Procedure or surgery | Intervention group - FESS |
Primary outcome
Change in The Sino-Nasal Outcome Test 22 (SNOTT22) score
Time frame: 6 months
The success rate indicated by a significant change in health-related quality of life related to nasal symptoms measured with the questionnaire SNOT22. The outcomes to be evaluated are the differences in success rates between the two treatment arms Minimum score = 0 and maximum score = 110 with high scores indicating a large rhinosinusitis-related health burden.
23 secondary outcomes
Change in Vo2max/kg(Cardiopulmonary exercise test )
Time frame: 6 and 12 motnhs folow-up
Change in Daily step count
Time frame: 6 and 12 months follow up
Change in Activity level(questionnaire)
Time frame: 6 and 12 months follow up
Change in Nasal Polyp Score (NPS)
Time frame: 3 and 6 months follow up
Change in Forced Expired Volume in the first second (FEV1)
Time frame: 6 and 12 months follow up
Change in forced vital capacity (FVC)
Time frame: 3, 6, and 12 months follow up
Change in Asthma Control Questionnaire (ACQ) score
Time frame: 3, 6, and 12 months follow up
Change in ratio between FEV1/FVC
Time frame: 3, 6, and 12 months follow up
Change in nitric oxide in exhaled air
Time frame: 6 and 12 months follow up
Change in middle ear pressure
Time frame: 12 months
Change in olfactory function
Time frame: 6 and 12 months follow up
Change in Functional Outcomes of Sleep Questionnaire (FOSQ) score
Time frame: 3, 6, and 12 months follow up
Change in Epworth Sleepiness score (ESS)
Time frame: 3, 6, and 12 months follow up
Change in AHI/ODI
Time frame: 6, and 12 months follow up
Change in Blood Eosinophilic cell count
Time frame: 3, 6, and 12 months follow up.
Change in Polyp Eosinophilic cell count
Time frame: 6 and 12 months follow up.
Change in Small airway dysfunction
Time frame: 6 and 12 months follow up.
Change in Bronchial hyperresponsiveness
Time frame: 6 and 12 months follow up
Change in eosinophilic cell count in sputum
Time frame: 6 and 12 months follow up
Change in NasalNO
Time frame: 6 and 12 months follow up
Change in visual analogue scale (VAS)
Time frame: 3, 6, and 12 months follow up
Change in visual analogue scale (VAS)
Time frame: 3, 6, and 12 months follow up
Change in visual analogue scale (VAS)
Time frame: 3, 6 and 12 months follow-up
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 30 Mar 2025.
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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. This study is not recruiting at the moment.
Vibeke B Backer, Professor study chair
Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Rigshospitalet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Mepolizumab Injection and Functional Endoscopic Sinus Surgery (FESS). in people with Chronic Rhinosinusitis with Nasal Polyps and Asthma, run by Vibeke Backer at 1 site in Denmark.
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 9 inclusion and 11 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: under way, not looking for participants, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in The Sino-Nasal Outcome Test 22 (SNOTT22) score (time frame: 6 months). 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 30 Mar 2025.