Skip to main content
OpenTrials
Active, Not Recruiting

NCT Number: NCT05598814

Mepolizumab to CRSwNP Through 12 Months - Randomised to FESS and Non-FESS Within the First 2 Weeks

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Chronic Rhinosinusitis With Nasal Polyps Asthma Bronchial Diseases Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Lung Diseases Lung Diseases, Obstructive Respiratory Hypersensitivity Respiratory Tract Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Rigshospitalet, Department of Otorhinolaryngology, Head and Neck Surgery & Audiology

Copenhagen, 2100, Denmark

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 surgery 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

Treatment and study plan

Mepolizumab Injection

Biological

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

The Functional Endoscopic Sinus Surgery will be performed 2 weeks after the first injection of Mepolizumab in the intervention group.

Primary outcomes

  1. 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.

Secondary outcomes

  1. Change in Vo2max/kg(Cardiopulmonary exercise test )

    Time frame: 6 and 12 motnhs folow-up

    Highest oxygen consumption measured on a stationary ergometer bike divided by body weight. MCID: 1 ml/min/kg

  2. Change in Daily step count

    Time frame: 6 and 12 months follow up

    Measured as an average daily step count over 7 days using a smartphone

  3. Change in Activity level(questionnaire)

    Time frame: 6 and 12 months follow up

    Patient's self-reported amount of exercise, measured using a questionnaire (customised AQUA)

  4. Change in Nasal Polyp Score (NPS)

    Time frame: 3 and 6 months follow up

    The NPS scale ranges from 0 (no polyp) to 4 (large polyps) for each nostril. The total score ranging from 0-8.

  5. Change in Forced Expired Volume in the first second (FEV1)

    Time frame: 6 and 12 months follow up

    Change in Forced Expired Volume in the first second (FEV1). The value is corrected for age, sex, height and weight.

  6. Change in forced vital capacity (FVC)

    Time frame: 3, 6, and 12 months follow up

    The value is corrected for age, sex, height and weight.

  7. Change in Asthma Control Questionnaire (ACQ) score

    Time frame: 3, 6, and 12 months follow up

    Change in ACQ-score. Minimum score = 0 and maximum score = 6 with high scores indicating a large asthma-related health burden.

  8. Change in ratio between FEV1/FVC

    Time frame: 3, 6, and 12 months follow up

    FEV1 divided by FVC. A ratio <0.70 is considered as obstructive.

  9. Change in nitric oxide in exhaled air

    Time frame: 6 and 12 months follow up

    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.

  10. Change in middle ear pressure

    Time frame: 12 months

    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.

  11. Change in olfactory function

    Time frame: 6 and 12 months follow up

    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.

  12. Change in Functional Outcomes of Sleep Questionnaire (FOSQ) score

    Time frame: 3, 6, and 12 months follow up

    FOSQ-10 consists of 10 questions rated on a scale of 1 to 4 (1=extreme difficulty and 4=no difficulty).

  13. Change in Epworth Sleepiness score (ESS)

    Time frame: 3, 6, and 12 months follow up

    ESS consists of 8 questions rated on a scale of 0 to 3 (3=extreme difficulty and 0=no difficulty)

  14. Change in AHI/ODI

    Time frame: 6, and 12 months follow up

    Measurement of objective sleep parameters (Apnea hypopnea index and Oxygen desaturation index)

  15. Change in Blood Eosinophilic cell count

    Time frame: 3, 6, and 12 months follow up.

    Blood Eosinophilic cell count from full blood cell count (109/mL).

  16. Change in Polyp Eosinophilic cell count

    Time frame: 6 and 12 months follow up.

    Tissue eosinophilia, classified into four categories: none (0), mild (<10 hpf), moderate (10-100 hpf), and severe (>100 hpf).

  17. Change in Small airway dysfunction

    Time frame: 6 and 12 months follow up.

    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.

  18. Change in Bronchial hyperresponsiveness

    Time frame: 6 and 12 months follow up

    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)

  19. Change in eosinophilic cell count in sputum

    Time frame: 6 and 12 months follow up

    Sputum induced through the inhalation of hypertonic saline at increasing concentrations (3%, 4%, and 5%). Percentual amount of Eosinophilic cells.

  20. Change in NasalNO

    Time frame: 6 and 12 months follow up

    A value greater then 255-300 is considered normal, whereas values less than 77 nl/min is abnormal.

  21. Change in visual analogue scale (VAS)

    Time frame: 3, 6, and 12 months follow up

    Change in VAS related to nasal symptoms. Minimum score = 0 and maximum score = 10. High score indicates worse nasal symptoms

  22. Change in visual analogue scale (VAS)

    Time frame: 3, 6, and 12 months follow up

    Change in VAS related to asthma symptoms. Minimum score = 0 and maximum score = 100. High score indicates worse Asthma symptoms

  23. Change in visual analogue scale (VAS)

    Time frame: 3, 6 and 12 months follow-up

    Change in VAS related to Smell. Minimum score = 0 and maximum score = 100. High score indicates worse Hyposmia Symptoms.

Sponsors and collaborators

Lead sponsor

Vibeke Backer

Other

Registry information

Official study 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

Important dates

Study start
2023
Primary completion
2024
Study completion
2025
First posted
Oct 28, 2022
Registry last updated
Mar 30, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.