Aggravated Airway Inflammation: Research on Genomics and Optimal Medical Care (AirGOs-medical)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Change in endoscopic Nasal polyp score of both sides of the nasal cavity.
研究概览
简要总结
The study is performed as a randomized double-blinded prospective controlled trial. A total of 72 adult Acetyl salicylic acid (ASA) -exacerbated respiratory disease (AERD) -patients with uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) will be recruited. Those negative to ASA-challenge test will not enter the Clinical Trial . All patients entering the Clinical Trial, have undergone earlier ethmoidal surgery (partial/total) and have not gained disease control. F-helicobacter antigen is tested and treatment is given if indicated. The patients are recruited at the Helsinki University Hospital (HUH). The study will be monitored by a professional monitor. Electronic CRF and paper/electronic patient questionnaires provided by HUS will be used (eCRF and patient questionnairea, Granitics).
详细描述
Randomization and the treatment arms I-II: The patients are randomized to two treatment arms I) ASA- desensitization po tablet daily for 11 months (n=36) II) Placebo po tablet daily for 11 months (n=18).
ASA challenge and desensitization (Primaspan) /Placebo: is conducted according to modified international protocol. FEV1 should be at least 1.5 L and > 60% of predicted before challenge or desensitization. On the first day every patient will receive 25 mg + 25 mg ASA at a hospital setting. On the second day every patient will receive 50 mg + 25 mg ASA at a hospital setting. On the third day every patient will receive 75 mg + 25 mg ASA at a hospital setting. On the fourth day every patient will receive 100 mg + 25 mg ASA at a hospital setting.
During the ASA challenge, patient who is ASA-challenge positive is then randomized and starts the trial so that he/she uses blinded ½ tablet of 250 mg ASA or ½ tablet of placebo daily at home for the next 1 month. After this period of 1 month, the dosing is increased at hospital setting, so that the patient receives blindly 250 mg ASA 1/2 tablet + 1/2 tablet or placebo 1/2 tablet + 1/2 tablet. Thereafter he/she will continue using blindly 250 mg ASA 1 tablet or placebo 1 tablet daily at home for the next 10 months. If the patient does not tolerate the up-dosing of ASA/placebo, he/she will continue using blindly ½ tablet of 250 mg ASA/placebo daily at home for the next 10 months. The total duration of the ASA/placebo treatment is 11 months. We additionally take nasal, blood and urine samples during the trial.
Follow-ups. The symptom questionnaire and interview of side-effects are performed during each visit. Lung function (eNO, nNO, PEF, spirometry) is monitored and the patient will visit doctor and/or nurse at 1, 5, 11, and 12 months post-starting with the treatment. Samples are taken during recruitment visit, before and after ASA-challenge and at 5, 11 and 12 months post-starting with the treatment. We also monitor side-effects, exacerbations, need of medication (po. cortisocteroids; antibiotics) and satisfaction to treatment.
Primary end point is change in nasal endoscopic nasal polyp score at -4 days vs. +11 months post-randomization. Secondary end point is change in Sinonasal Outcome Test -22 (SNOT-22) score at -4 days vs. +11 months post-randomization, and change in relative Forced expiratory volume in 1 second (FEV1 %) without bronchodilator at -1 month vs. +11 months post-randomization.
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 (Care Provider)
盲法说明
The IMP producer (Galena Pharma Ltd., Kuopio, Finland) has packed the IMP according to study protocol and provides a code of each product. The IMP is used double-blinded in their numbered order. The key of the codes are stored in closed envelopes in Hospital´s locked closet. HYKS-institute performs regular study monitoring
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ALL these need to be positive:
- •Endoscopic nasal polyp score ≥4
- •SNOT-22 ≥30
- •Sinus Computed tomography Lund-Mackay score ≥
- •The new sinus CT scans are needed if the previous sinus CT scans have been performed over 36 months before recruitment visit or if there is a suspicion of complication of CRS (f.ex. mucocele, invasive fungal rhinosinusitis)
- •≥1 previous partial/total ethmoidectomy surgery.
- •In addition, patient should have a history of at least one of the following:
- •>1 oral corticosteroids during the past two years >3 antibiotic courses during the past two years. In patients with contraindication/adverse effects in using oral steroids additional criteria are not required.
排除标准
- •complication of CRS (f.e. mucocele, invasive fungal rhinosinusitis)
- •bleeding diathesis
- •pregnancy/ breastfeeding
- •cystic fibrosis
- •primary ciliary dyskinesia (PCD)
- •sarcoidosis
- •granulomatosis with polyangitis (GPA)
- •eosinophilic granulomatosis with polyangitis (EGPA)
- •immunosuppression (diagnosed Spesific antibody deficiency (SAD), CVI, HIV
- •use of biologicals/immunosuppressive medication
- •immunotherapy
- •Daily use of systemic corticosteroids (Prednisolon 10mg or equivalent) -communication problems (f.e. neurological/psychiatric disease, language skills) -unlikely to comply
- •other severe disease
- •uncontrolled asthma
- •ASA-challenge negative
- •gastric ulcer
- •anticoagulant treatment
- •SSRI-depression medication
- •beta-blocker
- •severe chronic urticaria
- •ASA anaphylaxis
研究组 & 干预措施
Primaspan tablet 250 mg
Primaspan tablet 250 mg (Acetyl salicylic acid): 1/2 tablet once daily during 1 month. 1 tablet once daily during 10 months. If not tolerated the dose 1 tablet x1/day, the patient is allowed to continue with the dose of 1/2 tablet x1/day.
干预措施: Acetyl Salicylic Acid (Drug)
Placebo tablet
Placebo Oral Tablet: 1/2 tablet once daily during 1 month. 1 tablet once daily during 10 months. If not tolerated the dose 1 tablet x1/day, the patient is allowed to continue with the dose of 1/2 tablet x1/day.
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Change in endoscopic Nasal polyp score of both sides of the nasal cavity.
时间窗: at -4 days vs. at 11 months post-randomization
Change means differences between at time -4 days versus (vs.) at time +11 months post-randomization. Minimum value is 0. Maximum value is 8. A higher score means worse outcome.
次要结局
- Change in Sinonasal outcome test 22 (SNOT22). Validated nose-specific quality of life questionnaire, 0-110 points.(at -4 days vs. at 11 months post-randomization)
- Change in the Relative forced expiratory volume in 1 second (FEV1%) without bronchodilator.(at -1 month vs. at 11 months post-randomization)
研究者
Sanna Salmi
Senior Consultant Otorhinolaryngologist, PI
Helsinki University Central Hospital