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

Sponsor
Vibeke Backer (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05598814
Collaborator
(none)
52
Enrollment
2
Arms
27
Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: Mepolizumab Injection
  • Procedure: Functional Endoscopic Sinus Surgery (FESS).
 Phase 4

Study Design

Study Type:
Interventional
Anticipated Enrollment :
52 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
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.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 (Outcomes Assessor)
Masking Description:
The Nasal Polyp Score (NPS) evaluation will be performed by a third surgeon (blinded evaluation) who will not know the results of the screening visit and FESS/non-FESS randomisation.
Primary Purpose:
Treatment
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
Anticipated Study Start Date :
Jan 1, 2023
Anticipated Primary Completion Date :
Jun 1, 2024
Anticipated Study Completion Date :
Apr 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Intervention group - FESS

Biologic treatment with Mepolizumab and functional endoscopic sinus surgery (FESS).

Biological: Mepolizumab Injection
All patients in both the intervention group and the control group will be treated with Mepolizumab injections every month.

Procedure: 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.
Active Comparator: Control group - No-FESS

Biologic treatment with Mepolizumab

Biological: Mepolizumab Injection
All patients in both the intervention group and the control group will be treated with Mepolizumab injections every month.

Outcome Measures

Primary Outcome Measures

  1. Change in The Sino-Nasal Outcome Test 22 (SNOTT22) score [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 Outcome Measures

  1. Change in Nasal Polyp Score (NPS) [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.

  2. Change in Asthma Control Questionnaire (ACQ) score [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.

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

  4. Change in nitric oxide in exhaled air [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.

  5. Change in middle ear pressure [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.

  6. Change in olfactory function [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.

  7. Change in visual analogue scale (VAS) [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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • Vibeke Backer

Investigators

  • Study Chair: Vibeke B Backer, Professor, Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Rigshospitalet

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Vibeke Backer, Professor, Pulmonologist, MD, DMSc (PI), Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT05598814
Other Study ID Numbers:
  • 2022-ENT-FESS-nonFESS
First Posted:
Oct 28, 2022
Last Update Posted:
Nov 1, 2022
Last Verified:
Oct 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Additional relevant MeSH terms:
Nasal Polyps

Study Results

No Results Posted as of Nov 1, 2022