Methotrexate in the Treatment of Chronic Idiopathic Urticaria

Phase 3

Completed

• Conditions: Chronic Urticaria
• Interventions: Drug: Methotrexate (Novatrex ®) + anti-H1; Drug: Placebo + anti-H1

• Registration Number: NCT01960283
• Lead Sponsor: University Hospital, Tours

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.

Study Timeline

• Study Start: 2011-11
• Study First Submitted: 2013-01-15
• Study First Submitted QC: 2013-10-08
• Study First Posted: 2013-10-10
• Primary Completion: 2016-03
• Study Completion: 2016-05
• Status Verified: 2017-09
• Last Update Submitted: 2017-09-19
• Last Update Posted: 2017-09-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 83

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group I	Methotrexate (Novatrex ®) + anti-H1	The group I will receive the intervention : Methotrexate + anti-H1
Group II	Placebo + anti-H1	The intervention in group II will include : placebo + anti-H1

Primary Outcome Measures

Name	Time	Method
Number of patients with complete remission of urticaria at 18 weeks	at 18 weeks of treatment	Number of patients with complete remission of urticaria at 18 weeks, defined as no urticarial lesion 30 days before W18

Secondary Outcome Measures

Name	Time	Method
Efficacy of the treatment in improving symptoms : pruritus	18 weeks and 26 weeks	Number of patients with : - pruritus At 18 weeks and 26 weeks
Persistency of the complete remission at 26 weeks	26 weeks	Number of patients with persistency of the complete remission, defined as no urticarial lesion from the withdrawal of treatment until W26
Efficacy of the treatment in improving symptoms : duration of lesions	18 weeks and 26 weeks	- mean +/- standard deviation duration of lesions At 18 weeks and 26 weeks
Efficacy of the treatment in improving quality of sleep	18 weeks and 26 weeks	Mean score of quality of sleep (from 0 to 100) At 18 weeks and 26 weeks
Efficacy of the treatment in improving symptoms : outbreaks by week	18 weeks and 26 weeks	- number of outbreaks by week/patient At 18 weeks and 26 weeks
Efficacy of the treatment in improving quality of life	18 weeks and 26 weeks	Mean DLQI (quality of life) score : At 18 weeks and 26 weeks
Efficacy of the treatment in improving facial/cervical urticarial lesions	18 weeks and 26 weeks	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
Tolerance : clinical and biological safety	18 weeks	Number of patients with clinical adverse effects Number of patients with biological adverse effects

Trial Locations

Locations (11)

CHRU NANCY Brabois; 🇫🇷 Nancy, France

Chru Reims; 🇫🇷 Reims, France

CHRU BREST Morvan; 🇫🇷 Brest, France

Hopital TENON; 🇫🇷 Paris, France

Chru Nantes; 🇫🇷 Nantes, France

CHRU POITIERS La Miléterie; 🇫🇷 Poitiers, France

Chu Mondor; 🇫🇷 Créteil, France

Ch Le Mans; 🇫🇷 Le Mans, France

CHRU LILLE Huriez; 🇫🇷 Lille, France

CHRU RENNES Pontchaillou; 🇫🇷 Rennes, France

Chru Tours; 🇫🇷 Tours, France