Low-dose Methotrexate for Change in Global Initiative for Asthma Step 5 Medications in Chronic Severe Asthma

Universita degli Studi di Catania (Other)
Overall Status
Not yet recruiting
CT.gov ID

Study Details

Study Description

Brief Summary

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.

This study will be the first multi-centre RCT investigating the role of an add-on immunological modifier as a clinically useful therapeutic strategy in patients with well-phenotyped chronic severe asthma. As such, this study does not overlap with any other research currently ongoing.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

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 Step 5 medications (i.e. 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 matched placebo once a week as 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

Study Design

Study Type:
Anticipated Enrollment :
102 participants
Intervention Model:
Parallel Assignment
Double (Participant, Care Provider)
Primary Purpose:
Official Title:
Low-dose Methotrexate for Change in Global Initiative for Asthma Step 5 Medications in Chronic Severe Asthma: a Randomized Controlled Trial
Anticipated Study Start Date :
Dec 1, 2021
Anticipated Primary Completion Date :
Apr 1, 2022
Anticipated Study Completion Date :
Jul 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Methotrexate

Starting dose of 7.5 mg/week + folic acid the day after for 3 weeks as add-on therapy to their existing medication. Study treatment dosage will be increased, the maintenance dose will be 10 mg/week + folic acid the day after for 27 weeks

Drug: Methotrexate
7.5 mg/week + folic acid the day after
Other Names:
  • Several brand names
  • Placebo Comparator: Matched placebo

    Placebo pills

    Drug: Placebo
    matched placebo
    Other Names:
  • matched placebo
  • Outcome Measures

    Primary Outcome Measures

    1. At least 50% reduction in total dosage of GINA step 5 medications [80 weeks]

    Secondary Outcome Measures

    1. clinically significant changes in clinimetric scores [80 weeks]

    Eligibility Criteria


    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    Accepts Healthy Volunteers:
    Inclusion Criteria:
    1. patients with a diagnosis of CSA taking GINA Step 5 medications (i.e. regular OCS and/or omalizumab for a minimum of 6 months);

    2. failure in weaning patients completely from Step 5 medications during run-in;

    3. male and female individuals age 18 - 75 years;

    4. patients must be able to provide consent;

    Exclusion Criteria:
    1. use of immunomodulatory therapies in the preceding 3 months;

    2. recent or current history of alcoholism;

    3. high liver enzyme levels (greater than 2.5 times the upper limit of the normal range);

    4. serum creatinine levels greater than 2.0 mg/dL

    5. acute illness within 15 days of study medication administration;

    6. leucopenia (below 3.0x109/L) and/or thrombocytopenia (below 100x109/L).

    7. pregnancy or planning to become pregnant;

    Contacts and Locations


    No locations specified.

    Sponsors and Collaborators

    • Universita degli Studi di Catania


    • Principal Investigator: Riccardo Polosa, Full Professor, Universita di Catania

    Study Documents (Full-Text)

    None provided.

    More Information


    None provided.
    Responsible Party:
    Riccardo Polosa, Professor, Universita degli Studi di Catania
    ClinicalTrials.gov Identifier:
    Other Study ID Numbers:
    • METGINA-005
    First Posted:
    Apr 28, 2014
    Last Update Posted:
    Sep 28, 2021
    Last Verified:
    Sep 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Studies a U.S. FDA-regulated Device Product:
    Keywords provided by Riccardo Polosa, Professor, Universita degli Studi di Catania
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Sep 28, 2021