Methotrexate in the Treatment of Chronic Idiopathic Urticaria

Chronic Urticaria Clinical Trial

— MUCIS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01960283
• Other study ID #: PHRN09-AM/MUCIS
• Status: Completed
• Phase: Phase 3
• First received: January 15, 2013
• Last updated: September 19, 2017
• Start date: November 2011
• Est. completion date: May 2016

Study information

• Verified date: September 2017
• Source: University Hospital, Tours
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: May 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Urticaria
• Urticaria

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
France	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

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Tours

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with complete remission of urticaria at 18 weeks	Number of patients with complete remission of urticaria at 18 weeks, defined as no urticarial lesion 30 days before W18	at 18 weeks of treatment
Secondary	Tolerance : clinical and biological safety	Number of patients with clinical adverse effects Number of patients with biological adverse effects	18 weeks
Secondary	Efficacy of the treatment in improving symptoms : pruritus	Number of patients with : - pruritus At 18 weeks and 26 weeks	18 weeks and 26 weeks
Secondary	Persistency of the complete remission at 26 weeks	Number of patients with persistency of the complete remission, defined as no urticarial lesion from the withdrawal of treatment until W26	26 weeks
Secondary	Efficacy of the treatment in improving symptoms : outbreaks by week	- number of outbreaks by week/patient At 18 weeks and 26 weeks	18 weeks and 26 weeks
Secondary	Efficacy of the treatment in improving symptoms : duration of lesions	- mean +/- standard deviation duration of lesions At 18 weeks and 26 weeks	18 weeks and 26 weeks
Secondary	Efficacy of the treatment in improving quality of life	Mean DLQI (quality of life) score : At 18 weeks and 26 weeks	18 weeks and 26 weeks
Secondary	Efficacy of the treatment in improving quality of sleep	Mean score of quality of sleep (from 0 to 100) At 18 weeks and 26 weeks	18 weeks and 26 weeks
Secondary	Efficacy of the treatment in improving facial/cervical urticarial lesions	Number of patients with, either : facial/cervical urticarial lesions; urticarial lesions on the body only; facial/cervical + body lesions Indeed, facial or cervical urticarial lesions are considered more disturbing. At W18 and W26	18 weeks and 26 weeks