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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:
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention group - FESS | Experimental | Biologic treatment with Mepolizumab and functional endoscopic sinus surgery (FESS). |
|
| Control group - No-FESS | Active Comparator | Biologic treatment with Mepolizumab |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mepolizumab Injection | Biological | All patients in both the intervention group and the control group will be treated with Mepolizumab injections every month. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 6 and 12 motnhs folow-up |
| Change in Daily step count |
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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:
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:
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
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| Name | Affiliation | Role |
|---|---|---|
| Vibeke B Backer, Professor | Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Rigshospitalet | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rigshospitalet, Department of Otorhinolaryngology, Head and Neck Surgery & Audiology | Copenhagen | 2100 | Denmark |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| C434107 | mepolizumab |
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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.
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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.
| 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. |
|
Measured as an average daily step count over 7 days using a smartphone
| 6 and 12 months follow up |
| Change in Activity level(questionnaire) | Patient's self-reported amount of exercise, measured using a questionnaire (customised AQUA) | 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. | 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. | 6 and 12 months follow up |
| Change in forced vital capacity (FVC) | The value is corrected for age, sex, height and weight. | 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. | 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. | 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. | 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. | 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. | 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). | 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) | 3, 6, and 12 months follow up |
| Change in AHI/ODI | Measurement of objective sleep parameters (Apnea hypopnea index and Oxygen desaturation index) | 6, and 12 months follow up |
| Change in Blood Eosinophilic cell count | Blood Eosinophilic cell count from full blood cell count (109/mL). | 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). | 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. | 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) | 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. | 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. | 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 | 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 | 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. | 3, 6 and 12 months follow-up |
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |