Methotrexate in the Treatment of Chronic Idiopathic Urticaria

NCT ID: NCT01960283

Last Updated: 2017-09-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 83 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2016-05-31

Brief Summary

Chronic urticaria is defined by urticarial lesions persisting at 6 weeks. The cause is not found in about 75% of cases (chronic idiopathic urticaria). The gold standard treatment consists of anti-H1 molecules. In severe cases, refractory to anti-H1, few therapeutic alternatives exist. Methotrexate, which is not expensive and often prescribed by dermatologists, has been efficiently tried in an open study on severe chronic idiopathic urticaria, and also in few case reports.

Detailed Description

Chronic urticaria, defined by its persistence beyond 6 weeks, is a common condition (0.1% to 3% of the general population), occurring at any age. The etiology is not found in nearly 75% of cases (chronic idiopathic urticaria). Chronic idiopathic urticaria may resolve over several months or years. The quality of life of patients is usually strongly spoiled. The gold standard treatment consist of anti-H1 molecules. In severe cases, which are refractory to anti-H1, few therapeutic alternatives exist. Two studies have shown a benefit when adding to anti-H1, montelukast, anti-leukotriene, or cyclosporine. Methotrexate, which is another immunosuppressive drug, cheap and commonly prescribed by dermatologists, has been efficient in severe chronic urticaria, in an open study and in few case reports.

Methotrexate, an anti-metabolite drug which inhibits dihydrofolate reductase, is indicated in hematologic malignancies and in autoimmune diseases. It may be given by oral or parenteral administration, once a week, and requires regular monitoring of renal and hepatic function, and blood count.

Conditions

Chronic Urticaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Group I

The group I will receive the intervention :

Methotrexate + anti-H1

Group Type: ACTIVE_COMPARATOR

Methotrexate (Novatrex ®) + anti-H1

Intervention Type: DRUG

Methotrexate (Novatrex ®) tablets 2.5 mg methotrexate 0.2 mg/kg/week as a single dose, orally for 8 weeks.

After 8 weeks, if the treatment is still not efficient, the dose will be increased to 0.25 mg/kg/week and continued until W18.

For anti-H1 treatment, the same molecules with the same dosage than before the recruitment will be continued, and methotrexate will be added in this group.

Group II

The intervention in group II will include : placebo + anti-H1

Group Type: PLACEBO_COMPARATOR

Placebo + anti-H1

Intervention Type: DRUG

Placebo: 0.2 mg / kg / week as a single dose, orally for 8 weeks. After eight weeks, if the patient is still very embarrassed, the dose is increased to 0.25 mg / kg / week in a weekly dose.

For anti-H1 treatment, the same molecules with the same dosage than before the recruitment will be continued, and the placebo of methotrexate will be added in this group.

Interventions

Methotrexate (Novatrex ®) + anti-H1

Methotrexate (Novatrex ®) tablets 2.5 mg methotrexate 0.2 mg/kg/week as a single dose, orally for 8 weeks.

After 8 weeks, if the treatment is still not efficient, the dose will be increased to 0.25 mg/kg/week and continued until W18.

For anti-H1 treatment, the same molecules with the same dosage than before the recruitment will be continued, and methotrexate will be added in this group.

Intervention Type: DRUG

Placebo + anti-H1

Placebo: 0.2 mg / kg / week as a single dose, orally for 8 weeks. After eight weeks, if the patient is still very embarrassed, the dose is increased to 0.25 mg / kg / week in a weekly dose.

For anti-H1 treatment, the same molecules with the same dosage than before the recruitment will be continued, and the placebo of methotrexate will be added in this group.

Intervention Type: DRUG

Other Intervention Names

Methotrexate; Anti-H1; Placebo of methetrexate + anti-H1

Eligibility Criteria

Inclusion Criteria

Patients who met the diagnostic criteria for chronic idiopathic urticaria, previously treated by

• 3 different molecules of anti-H1 or
• a combination of 2 different molecules of anti-H1 or
• 1 molecule of anti-H1 with at least a double dose for a total treatment duration of ≥ 3 months before inclusion
• With persistency of at least 7 days with urticarial lesions in the previous month

Exclusion Criteria

• Differential diagnosis of chronic idiopathic urticaria (urticarial vasculitis)
• Treatment with montelukast or immunosuppressive drugs during the previous month
• Contraindications to methotrexate

• Allergy to methotrexate
• Treatment which are contraindicated with methotrexate
• Pregnancy, possibility of getting pregnant (no effective contraception), breastfeeding
• Anomalies in liver function (transaminases or liver failure at a rate 1.5 X normal)
• Severe renal impairment (creatinine clearance calculated by the cockcroft formula <50 ml / min)
• Chronic respiratory failure
• Active infectious chronic diseases (viral hepatitis, HIV)
• History of neoplasia
• Mental deficiency
• Involvement in another drug clinical trial

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Tours

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Annabel MARUANI, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Tours, France

Locations

CHRU BREST Morvan

Brest, , France

Chu Mondor

Créteil, , France

Ch Le Mans

Le Mans, , France

CHRU LILLE Huriez

Lille, , France

CHRU NANCY Brabois

Nancy, , France

Chru Nantes

Nantes, , France

Hopital TENON

Paris, , France

CHRU POITIERS La Miléterie

Poitiers, , France

Chru Reims

Reims, , France

CHRU RENNES Pontchaillou

Rennes, , France

Chru Tours

Tours, , France

Countries

France

Other Identifiers

PHRN09-AM/MUCIS

Identifier Type: -

Identifier Source: org_study_id