English Title: Complete Remission Study Subtitle: Discontinuation of Mepolizumab or Dupilumab After at Least 12 Months Without Symptoms in Patients With Severe Chronic Rhinosinusitis With Polyps - a National Danish RCT Study
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 66
- 试验地点
- 6
- 主要终点
- Number of patients who can continue being in complete remission being out of biologic treatment.
研究概览
简要总结
In this RCT the investigators randomize patients who are treated with biologic treatment (Nucala or Dupixent) due to nasal polyps and have controlled disease within the last year to either stop treatment og continue as a control group.
详细描述
11 Protocol Synopsis 11.1. EU trial number and full trial title: 2024- 5196285-25-00 English title: Complete remission study Subtitle: Discontinuation of Mepolizumab or Dupilumab after at least 12 months without symptoms in patients with severe Chronic rhinosinusitis with polyps - a National Danish RCT study.
11.2. Rationale Specify background and hypothesis of the trial. The Danish Medicines Council has decided that well-controlled patients with nasal polyps should try to cease the medication after two years of treatment with biologics (Mepolizumab or Dupilumab). The investigators find this better to do in a RCT. Based on the experience from asthma patients this could be done in some patients without the symptoms reoccur.
11.3. Objective Specify the main and secondary objectives of the trial. The main objective is to find the percentage of patients in complete remission (no or few symptoms) who can cease the biologic treatment and keep being in remission. The secondary objective is to observe if one or the other drug is more likely to give this result.
11.4. & 11.5 Main and secondary trial endpoints: The main endpoint is to monitor the percentage of patients who do not have recurrence of their sino-nasal symptoms when they cease medicine. This is evaluated at baseline and after 12,26,38,52 weeks, however, the patients can contact the investigators at any time if symptoms reoccur. A control group is included and it is assumed that patients kept on treatment will keep being in complete remission. No adverse effects are expected, thus no new medication is started.
11.6. Trial design: Non-blinded, prospective RCT. Half the included patients will keep their treatment unchanged (control-group) the other half will stop the biological treatment (everything else unchanged). Every individual participant will have a 52-week follow-up period. If a participant in the trial group gets symptoms and feel partly uncontrolled they will start treatment again with same drug, dose and interval as before the cease.
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
- None
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
- •5.1 Inclusion criteria (all must be fulfilled)
- •Inclusion criteria:
- •At the time when the patient started biological treatment, they must have fulfilled the EPOS criteria for initiation of biologic treatment (REF EPOS):
- •Fulfil the criteria for CRSwNP
- •Presence of bilateral polyps in a patient
- •Had ESS (sinus surgery) (exceptional circumstances excluded)
- •Fulfil at least three of the following five criteria Evidence of type 2 inflammation Need for (and treated with) systemic corticosteroids or contraindication to these SNOT-22 score of 40 or above Significant loss of smell Asthma needing regular inhaled corticosteroids
- •To enter this study, the patient must be:
- •Above 18 years of age
- •Currently be in treatment with either Dupilumab (300 mg) or Mepolizumab (100 mg) with treatment every fourth week. This treatment should have been stable/unchanged for at least three months.
- •Within the latest year, the patient must at all times have scored all the below symptoms of CRS five or below on a VAS scale from 0 - 10 - Doing this, it is according to the EPOS defined as controlled disease. The items are: nasal blockage, rhinorrhea/postnasal drip, facial pain/pressure, smell, sleep disturbance or fatigue) Please view appendix
- •Within the latest year the nasal endoscopy cannot have showed polyp score of more than 1+1 out of 4+4, further, no thick secretions or general oedema must have been present.
- •Within the latest year the patient is not allowed to have had ESS or rescue treatment for their CRSwNP (antibiotics or systemic steroids)
- •The patient must be able to understand Danish and able to sign an informed content.
排除标准
- •In the twelve months of remission the patient is not allowed to have had AECRS (acute exacerbation of chronic rhinosinusitis). A common cold is allowed.
- •Polyp removal in the out-patient clinic may not have been performed within the last 3 months.
- •In the twelve months of remission the patient cannot at any time have scored higher than 1.2 on the ACQ questionnaire, meaning that the patient does not have uncontrolled asthma (Appendix 3).
- •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 (asthma not included)
- •Patients who are not able to give informed consent (i.e., patients who are permanently incapable)
- •Patients who are not eligible because of the investigator's judgement
- •Patients who experience pregnancy during the study will be excluded after an unscheduled visit (LOCF) - active IVF treatment. (Please look belove)
- •Patients who have or recently have had illness, such as cancer that or its treatment is expected to significantly affect morbidity and/or quality of life in the next two years
- •Unwillingness to follow the study procedure
- •Hypersensitivity to any of either Dupilumab or Mepolizumab.
研究组 & 干预措施
Arm 1: Continue Drug D
Participants continue their usual treatment with Drug Dupi throughout the study.
干预措施: DUPIXENT® (Drug)
Arm 2: Stop Drug D
Participants discontinue Drug Dupi at baseline and receive no active treatment during the study.
干预措施: Dupi discontinuation (Other)
Arm 3: Continue Drug M
Participants continue their usual treatment with Drug Mepo throughout the study.
干预措施: NUCALA® (Drug)
Arm 4: Stop Drug M
Participants discontinue Drug Mepo at baseline and receive no active treatment during the study.
干预措施: Mepo discontinuation (Other)
结局指标
主要结局
Number of patients who can continue being in complete remission being out of biologic treatment.
时间窗: One year observaton
It is known that some asthma patients after years of treatment can stop taking biologics without regaining symptoms. Further, studies have shown that a lot of patients can be without symptoms taking biologics every 12th week. The definition of being in control, also called complete remission, is: not scoring higher than 5 (range 0 -10) on a Visual Analogue Scale (VAS) on nasal blockage, rhinorrhea, facial pressure, decreased smell or sleep; 0 being no symptoms and 10 being worst imaginable further no antibiotics, systemic steroids or surgery should be needed and the nasal examination must also be unchanged. The primary outcome is to observe how many, if any, patients can stop their biologic treatment still being in complete remission. This is evaluated by VAS questionnaires and nasal endoscopy every third month or even more frequent if the patient has symptoms. This is compared with the control group that has the same follow-up regime.
次要结局
- Is there any difference in what drug (Dupixent or Nucala) the patient was treated with before they stopped in the ability to obtain complete remission(One year observation)
研究者
Kasper Aanaes
Medical doctor, phd., Principal investigator, associated professor
Rigshospitalet, Denmark