Clinical trial NCT03789422: Tranexamic Acid and Spontaneous Chronic Urticaria
Official title: Efficacy and Safety of Levocetirizine Alone or in Combination With Tranexamic Acid in the Treatment of Spontaneous Chronic Urticaria. Multicentric Controlled Randomized Study in Cross-over, Double-blind
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Spontaneous Urticaria
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
First posted: 2018-12-28
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Multicentric controlled randomized crossover study, double-blind
Primary purpose: TREATMENT

Brief summary: Spontaneous chronic urticaria (UCS) is a disease that affects 1% of the general population with a potentially severe impact on quality of life. Most patients respond favorably to long-term antihistamine treatment, but sometimes it is necessary to give a high dose (4 times the formal dose, Berlin consensus 2016). These high doses are often accompanied by side effects requiring cessation of treatment. The therapeutic alternative is then omalizumab, an expensive biotherapy. UCS is secondary to non-specific mast cell activation. It has been shown to be associated with activation of fibrinolysis that correlates with the severity of symptoms. Patients with UCS resistant to levocetirizine were shown to have higher D-dimer levels than patients who responded to antihistamines. Tranexamic acid is a molecule with antifibrinolytic propertiesSeveral cases of severe chronic urticaria responding favorably to treatment with tranexamic acid have been reported. In our department, Investigators also noticed the improvement of some of their patients on tranexamic acid. The combination of these two treatments appears to be synergistic: action on histamine receptors and control of fibrinolysis.

The investigators propose to evaluate the association of tranexamic acid and levocetirizine for the treatment of chronic spontaneous urticaria.

Detailed description: Multicentric controlled randomized crossover study, double-blind To evaluate the efficacy and safety of levocetirizine 10mg / day + tranexamic acid (AT) 2g / day versus levocetirizine 20mg / day alone in the chronic treatment of chronic urticaria evaluated at 4 weeks.

A hierarchical analysis will be implemented in the following order:

1. Non-inferiority of the combination levocetirizine 10 mg / day + tranexamic acid (TA) 2 g / day versus levocetirizine alone 20 mg / day in terms of effectiveness
2. Superiority of the combination levocetirizine 10 mg / day + tranexamic acid (AT) 2 g / day versus levocetirizine alone 20 mg / day in terms of tolerance
3. Superiority of levocetirizine 10mg / day + tranexamic acid (AT) 2g / day versus levocetirizine alone 20mg / day in terms of effectiveness Each objective will be tested sequentially if and only if the previous objective is validated.

Eligibility criteria: Inclusion Criteria:

* Patients with spontaneous chronic urticaria, according to the criteria of the European Academy of Allergology and Clinical Immunology (EAACI) in agreement with the European Dermatology Forum (EDF), and the World Allergy Organization (WAO), corresponding to an association of the following symptoms : urticarial eruptions and / or recurrent angioedema for at least 6 weeks

Exclusion Criteria:

* Urticaria associated with a specific systemic disease including cutaneous and systemic mastocytosis, urticarial vasculitis, autoinflammatory diseases associated with cryopyrin
* Bradykinin angioedema and isolated angioedema whose origin is not clearly attributable to spontaneous chronic urticaria.
* Presence of a contraindication to tranexamic acid and to levocetirizine

Primary outcomes:
measure: Evolution of the Urticaria Activity Score 7 (UAS7)
timeFrame: 28 days
measure: Tolerance of the association tranexamic acid and levocetirizine
timeFrame: 28 days
Secondary outcomes:
measure: To demonstrate the non-inferiority of levocetirizine 10mg / day + tranexamic acid (AT) 2g / day versus levocetirizine alone 20mg / day in terms of efficacy on the Angioedema Activity Score (AAS)
timeFrame: 28 days
measure: Clinical characteristics of responders
timeFrame: 28 days
Other outcomes:
Locations:
city: Grenoble
country: France
facility: CHU Grenoble-Alpes
Study officials:
affiliation: Internal Medicine - University Hospital Grenoble-Alpes
name: Laurence BOUILLET, PhD
role: PRINCIPAL_INVESTIGATOR
References: