Clinical trial NCT05598814: Mepolizumab to CRSwNP Through 12 Months - Randomised to FESS and Non-FESS Within the First 2 Weeks
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Chronic Rhinosinusitis with Nasal Polyps
Asthma
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2022-10-28
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief 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).

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in The Sino-Nasal Outcome Test 22 (SNOTT22) score
timeFrame: 6 months
Secondary outcomes:
measure: Change in Vo2max/kg(Cardiopulmonary exercise test )
timeFrame: 6 and 12 motnhs folow-up
measure: Change in Daily step count
timeFrame: 6 and 12 months follow up
measure: Change in Activity level(questionnaire)
timeFrame: 6 and 12 months follow up
measure: Change in Nasal Polyp Score (NPS)
timeFrame: 3 and 6 months follow up
measure: Change in Forced Expired Volume in the first second (FEV1)
timeFrame: 6 and 12 months follow up
measure: Change in forced vital capacity (FVC)
timeFrame: 3, 6, and 12 months follow up
measure: Change in Asthma Control Questionnaire (ACQ) score
timeFrame: 3, 6, and 12 months follow up
measure: Change in ratio between FEV1/FVC
timeFrame: 3, 6, and 12 months follow up
measure: Change in nitric oxide in exhaled air
timeFrame: 6 and 12 months follow up
measure: Change in middle ear pressure
timeFrame: 12 months
measure: Change in olfactory function
timeFrame: 6 and 12 months follow up
measure: Change in Functional Outcomes of Sleep Questionnaire (FOSQ) score
timeFrame: 3, 6, and 12 months follow up
measure: Change in Epworth Sleepiness score (ESS)
timeFrame: 3, 6, and 12 months follow up
measure: Change in AHI/ODI
timeFrame: 6, and 12 months follow up
measure: Change in Blood Eosinophilic cell count
timeFrame: 3, 6, and 12 months follow up.
measure: Change in Polyp Eosinophilic cell count
timeFrame: 6 and 12 months follow up.
measure: Change in Small airway dysfunction
timeFrame: 6 and 12 months follow up.
measure: Change in Bronchial hyperresponsiveness
timeFrame: 6 and 12 months follow up
measure: Change in eosinophilic cell count in sputum
timeFrame: 6 and 12 months follow up
measure: Change in NasalNO
timeFrame: 6 and 12 months follow up
measure: Change in visual analogue scale (VAS)
timeFrame: 3, 6, and 12 months follow up
measure: Change in visual analogue scale (VAS)
timeFrame: 3, 6, and 12 months follow up
measure: Change in visual analogue scale (VAS)
timeFrame: 3, 6 and 12 months follow-up
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet, Department of Otorhinolaryngology, Head and Neck Surgery & Audiology
Study officials:
affiliation: Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Rigshospitalet
name: Vibeke B Backer, Professor
role: STUDY_CHAIR
References: