Clinical trial NCT01960283: Methotrexate in the Treatment of Chronic Idiopathic Urticaria
Official title: Randomized Clinical Trial Evaluating the Efficacy of Methotrexate in Addition to Anti-H1 Versus Placebo and Anti-H1 in the Treatment of Severe Chronic Idiopathic Urticaria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Urticaria
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
First posted: 2013-10-10
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of patients with complete remission of urticaria at 18 weeks
timeFrame: at 18 weeks of treatment
Secondary outcomes:
measure: Tolerance : clinical and biological safety
timeFrame: 18 weeks
measure: Efficacy of the treatment in improving symptoms : pruritus
timeFrame: 18 weeks and 26 weeks
measure: Persistency of the complete remission at 26 weeks
timeFrame: 26 weeks
measure: Efficacy of the treatment in improving symptoms : outbreaks by week
timeFrame: 18 weeks and 26 weeks
measure: Efficacy of the treatment in improving symptoms : duration of lesions
timeFrame: 18 weeks and 26 weeks
measure: Efficacy of the treatment in improving quality of life
timeFrame: 18 weeks and 26 weeks
measure: Efficacy of the treatment in improving quality of sleep
timeFrame: 18 weeks and 26 weeks
measure: Efficacy of the treatment in improving facial/cervical urticarial lesions
timeFrame: 18 weeks and 26 weeks
Other outcomes:
Locations:
city: Brest
country: France
facility: CHRU BREST Morvan
city: Créteil
country: France
facility: Chu Mondor
city: Le Mans
country: France
facility: Ch Le Mans
city: Lille
country: France
facility: CHRU LILLE Huriez
city: Nancy
country: France
facility: CHRU NANCY Brabois
city: Nantes
country: France
facility: Chru Nantes
city: Paris
country: France
facility: Hopital TENON
city: Poitiers
country: France
facility: CHRU POITIERS La Miléterie
city: Reims
country: France
facility: Chru Reims
city: Rennes
country: France
facility: CHRU RENNES Pontchaillou
city: Tours
country: France
facility: Chru Tours
Study officials:
affiliation: University Hospital of Tours, France
name: Annabel MARUANI, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: