title: Weekly low-dose methotrexate for reduction of Global Initiative for Asthma Step 5 treatment in severe refractory asthma: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  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
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT02124226 (assigned 25 April 2014).
authors.affiliation: Department of Clinical and Biomolecular Medicine, University of Catania, Ospedale Garibaldi Nesima, 636 Via Palermo, 95122 Catania, Italy. polosa@unict.it.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Polosa
authors.forename: Salvatore
authors.initials: S
authors.lastname: Bellinvia
authors.forename: Massimo
authors.initials: M
authors.lastname: Caruso
authors.forename: Rosalia
authors.initials: R
authors.lastname: Emma
authors.forename: Angela
authors.initials: A
authors.lastname: Alamo
authors.forename: Marek Leszek
authors.initials: ML
authors.lastname: Kowalski
authors.forename: Christian
authors.initials: C
authors.lastname: Domingo
mesh_terms: D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D002908:Chronic Disease; D002985:Clinical Protocols; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007558:Italy; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D012107:Research Design; D012720:Severity of Illness Index; D062606:Tertiary Care Centers; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018927:Anti-Asthmatic Agents; D007166:Immunosuppressive Agents; D008727:Methotrexate