Polosa Riccardo, Bellinvia Salvatore, Caruso Massimo, Emma Rosalia, Alamo Angela, Kowalski Marek Leszek, Domingo Christian
Department of Clinical and Biomolecular Medicine, University of Catania, Ospedale Garibaldi Nesima, 636 Via Palermo, 95122 Catania, Italy.
Trials. 2014 Dec 18;15:492. doi: 10.1186/1745-6215-15-492.
Patients with chronic severe asthma (CSA) have a crippling disease and current available treatments are not satisfactory. Thus, management of CSA remains a major unmet need. Although the evidence from existing randomized controlled trials fails to support a definite role for immunomodulatory drugs in these patients due to major methodologic drawbacks, findings with low-dose methotrexate (MTX) are encouraging. However, larger and well-designed clinical trials are required to establish the beneficial role of MTX in CSA, and for the detection of the key characteristics of those who are going to respond to this drug.
METHODS/DESIGN: Patients will be recruited from the accessible asthmatic patients lists of tertiary referral centers. All patients will meet the stringent diagnostic criteria for CSA, including the requirement for the regular use of Global Initiative for Asthma (GINA) Global Strategy for Asthma Management and Prevention Step 5 medications (oral prednisone and/or omalizumab). The experimental design of the proposed study will take the form of a double-blind parallel-randomized placebo-controlled trial consisting of a total of eight visits, including run-in and run-out periods. Patients will be randomly allocated to receive either MTX or a matched placebo once a week as an add-on therapy to their existing medication after run-in. Physiological, laboratory and clinical assessments will be measured regularly throughout the study and compared with baseline assessments.
We expect that MTX will reduce Step 5 medications dosage in patients with CSA without compromising the overall disease control. Improvement in several indicators of asthma severity and control will be also investigated.
ClinicalTrials.gov Identifier: NCT02124226 (assigned 25 April 2014).
慢性重度哮喘（CSA）患者患有严重疾病，目前可用的治疗方法并不令人满意。因此，CSA的管理仍然是一个主要的未满足需求。尽管现有随机对照试验的证据由于主要的方法学缺陷而未能支持免疫调节药物在这些患者中的明确作用，但低剂量甲氨蝶呤（MTX）的研究结果令人鼓舞。然而，需要更大规模且设计良好的临床试验来确定MTX在CSA中的有益作用，并检测那些对该药物有反应的患者的关键特征。
方法/设计：将从三级转诊中心可获取的哮喘患者名单中招募患者。所有患者将符合CSA的严格诊断标准，包括定期使用全球哮喘防治创议（GINA）《哮喘管理和预防全球策略》第5步药物（口服泼尼松和/或奥马珠单抗）的要求。拟议研究的实验设计将采用双盲平行随机安慰剂对照试验的形式，共包括八次访视，包括导入期和洗脱期。患者在导入期后将被随机分配，每周接受一次MTX或匹配的安慰剂，作为其现有药物的附加治疗。在整个研究过程中定期进行生理、实验室和临床评估，并与基线评估进行比较。
我们预计MTX将降低CSA患者的第5步药物剂量，而不会影响整体疾病控制。还将研究哮喘严重程度和控制的几个指标的改善情况。
ClinicalTrials.gov标识符：NCT02124226（2014年4月25日分配）。
