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
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Change in The Sino-Nasal Outcome Test 22 (SNOTT22) score
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Control group - No-FESS
Biologic treatment with Mepolizumab
干预措施: Mepolizumab Injection (Biological)
Intervention group - FESS
Biologic treatment with Mepolizumab and functional endoscopic sinus surgery (FESS).
干预措施: Mepolizumab Injection (Biological)
Intervention group - FESS
Biologic treatment with Mepolizumab and functional endoscopic sinus surgery (FESS).
干预措施: Functional Endoscopic Sinus Surgery (FESS). (Procedure)
结局指标
主要结局
Change in The Sino-Nasal Outcome Test 22 (SNOTT22) score
时间窗: 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.
次要结局
- Change in Vo2max/kg(Cardiopulmonary exercise test )(6 and 12 motnhs folow-up)
- Change in Daily step count(6 and 12 months follow up)
- Change in Activity level(questionnaire)(6 and 12 months follow up)
- Change in Nasal Polyp Score (NPS)(3 and 6 months follow up)
- Change in Forced Expired Volume in the first second (FEV1)(6 and 12 months follow up)
- Change in forced vital capacity (FVC)(3, 6, and 12 months follow up)
- Change in Asthma Control Questionnaire (ACQ) score(3, 6, and 12 months follow up)
- Change in ratio between FEV1/FVC(3, 6, and 12 months follow up)
- Change in nitric oxide in exhaled air(6 and 12 months follow up)
- Change in middle ear pressure(12 months)
- Change in olfactory function(6 and 12 months follow up)
- Change in Functional Outcomes of Sleep Questionnaire (FOSQ) score(3, 6, and 12 months follow up)
- Change in Epworth Sleepiness score (ESS)(3, 6, and 12 months follow up)
- Change in AHI/ODI(6, and 12 months follow up)
- Change in Blood Eosinophilic cell count(3, 6, and 12 months follow up.)
- Change in Polyp Eosinophilic cell count(6 and 12 months follow up.)
- Change in Small airway dysfunction(6 and 12 months follow up.)
- Change in Bronchial hyperresponsiveness(6 and 12 months follow up)
- Change in eosinophilic cell count in sputum(6 and 12 months follow up)
- Change in NasalNO(6 and 12 months follow up)
- Change in visual analogue scale (VAS)(3, 6 and 12 months follow-up)
研究者
Vibeke Backer
Professor, Pulmonologist, MD, DMSc (PI)
Rigshospitalet, Denmark