Low Dose Methotrexate in Severe Chronic AsthmaPhase 3NCT02124226
Low-dose Methotrexate for Change in Global Initiative for Asthma Step 5 Medications in Chronic Severe Asthma
A Phase 3 study testing Methotrexate in people with Low Dose Methotrexate in Severe Chronic Asthma, run by University of Catania.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Low Dose Methotrexate in Severe Chronic Asthma
- What is being tested?
- Methotrexate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 102 participants
- Where
- No sites listed yet
- Study dates
- Dec 2021to Jul 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- patients with a diagnosis of CSA taking GINA Step 5 medications (i.e. regular OCS and/or omalizumab for a minimum of 6 months);
- failure in weaning patients completely from Step 5 medications during run-in;
- male and female individuals age 18 - 75 years;
- patients must be able to provide consent;
Who cannot join
- use of immunomodulatory therapies in the preceding 3 months;
- recent or current history of alcoholism;
- high liver enzyme levels (greater than 2.5 times the upper limit of the normal range);
- serum creatinine levels greater than 2.0 mg/dL
- acute illness within 15 days of study medication administration;
- leucopenia (below 3.0x109/L) and/or thrombocytopenia (below 100x109/L).
- pregnancy or planning to become pregnant;
About this study
Official title: Low-dose Methotrexate for Change in Global Initiative for Asthma Step 5 Medications in Chronic Severe Asthma: a Randomized Controlled Trial
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.
Read the 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
- Being tested
- Methotrexate, Placebo
- Keywords
- Chronic severe asthma, immunomodulation, methotrexate, steroids, omalizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
Also called Several brand names
7.5 mg/week + folic acid the day after
PlaceboDrug
Also called matched placebo
matched placebo
| Study group | Role | What they receive |
|---|---|---|
| Methotrexate | Experimental | 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 Receives: Drug: Methotrexate |
| Matched placebo | Placebo comparator | Placebo pills Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
At least 50% reduction in total dosage of GINA step 5 medications
Measured: 80 weeks
Secondary outcomes (1)
clinically significant changes in clinimetric scores
Measured: 80 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2014 (estimated)
- Study startDec 2021 (estimated)
- Primary completionApr 2022 (estimated)
- Study completionJul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Low Dose Methotrexate in Severe Chronic AsthmaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 102 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Catania
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Riccardo Polosa, University of Catania
- Investigators
- Riccardo Polosa, Full Professor, Principal investigator, Universita di Catania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02124226
- Sponsor's protocol ID
- METGINA-005
- Status last verified
- Sep 2021
- First submitted
- 24 Apr 2014
- Last updated
- 28 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Polosa R, Bellinvia S, Caruso M, Emma R, Alamo A, Kowalski ML, Domingo C. 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. Trials. 2014 Dec 18;15:492. doi: 10.1186/1745-6215-15-492.
PubMed 25523634
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low-dose Methotrexate for Change in Global Initiative for Asthma Step 5 Medications in Chronic Severe Asthma: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT02124226
- Acronym / sponsor ID
- METGINA-005
- Keywords
- Chronic severe asthma, immunomodulation, methotrexate, steroids, omalizumab
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 102 participants (estimated)
- Lead sponsor
- University of CataniaUniversity, hospital or other
- Study start
- Dec 2021 (estimated)
- Primary completion
- Apr 2022 (estimated)
- Study completion
- Jul 2022 (estimated)
- First posted
- 28 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methotrexate | Experimental | Drug: MethotrexateStarting 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 |
| Matched placebo | Placebo comparator | Drug: PlaceboPlacebo pills |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- patients with a diagnosis of CSA taking GINA Step 5 medications (i.e. regular OCS and/or omalizumab for a minimum of 6 months);
- failure in weaning patients completely from Step 5 medications during run-in;
- male and female individuals age 18 - 75 years;
- patients must be able to provide consent;
Key exclusion criteria (7 listed)
- use of immunomodulatory therapies in the preceding 3 months;
- recent or current history of alcoholism;
- high liver enzyme levels (greater than 2.5 times the upper limit of the normal range);
- serum creatinine levels greater than 2.0 mg/dL
- acute illness within 15 days of study medication administration;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethotrexateAlso: Several brand names7.5 mg/week + folic acid the day after | Drug | Methotrexate |
| PlaceboAlso: matched placebomatched placebo | Drug | Matched placebo |
Primary outcome
At least 50% reduction in total dosage of GINA step 5 medications
Time frame: 80 weeks
1 secondary outcome
clinically significant changes in clinimetric scores
Time frame: 80 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2021.
- Derived from this study: PubMed 25523634Polosa R, Bellinvia S, Caruso M, Emma R, Alamo A, Kowalski ML, Domingo C. 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. Trials. 2014 Dec 18;15:492. doi: 10.1186/1745-6215-15-492.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Riccardo Polosa, Full Professor principal investigator
Universita di Catania
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Methotrexate in people with Low Dose Methotrexate in Severe Chronic Asthma, run by University of Catania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
At least 50% reduction in total dosage of GINA step 5 medications (time frame: 80 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02124226, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2021.