Tranexamic Acid and Spontaneous Chronic Urticaria (TACUS)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Spontaneous Urticaria
• Intervention / Treatment: Drug: association of levocetirizine and tranexamic acid; Drug: Levocetirizine only

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.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Raouf ZOUGLECH, MDS; Phone Number: 0033 4 76 76 78 38; Email: rzouglech@chu-grenoble.fr
• Study Contact Backup: Name: Tiphaine Montagnon; Phone Number: 0033 4 76 76 68 14; Email: tmontagnon@chu-grenoble.fr

Study Locations

• France
  • Grenoble, France, 38043
    • Recruiting
    • CHU Grenoble-Alpes
    • Contact: Mélanie Arnaud; Phone Number: 0033 4 76 76 78 38
    • Principal Investigator: Laurence BOUILLET, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Association drugs; levocetirizine 10mg/day + tranexamic acid (AT) 2g/day for a month	Drug: association of levocetirizine and tranexamic acid; levocetirizine 10 mg/day + tranexamic acid 2 g/day
Active Comparator: one drug; Levocetirizine 20 mg/day for a month	Drug: Levocetirizine only; levocetirizine 20 mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evolution of the Urticaria Activity Score 7 (UAS7)	Evolution of the UAS7 score between the beginning (J0) and the end (J28) of the treatment period. To calculate the score, the patient rates the number of papules and itching intensity from 0 to 3 daily for 7 days. 0 corresponds to no papules and no itching, 3 corresponds to more than 50 papules per 24h and intense itching that can cause daily life. This makes a score of 0 to 6 per day accumulated over 7 days, ranging from 0 to 42.	28 days
Tolerance of the association tranexamic acid and levocetirizine	Number of adverse events	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Evolution of the AAS score between the beginning (J0) and the end (J28) of the end of treatment. The AAS score is a The AAS consists of 5 questions as well as an opening question. A score between 0 and 3 is assigned to every answer field. The question scores are summed up to an AAS day sum score, 7 AAS day sum scores to an AAS week sum score (AAS7). Accordingly, the minimum and maximum possible AAS scores are 0-15 (AAS day sum score), 0-105 (AAS7).	28 days
Clinical characteristics of responders	Identify the clinical characteristics of responders to the combination rather than antihistamines alone.	28 days

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Investigators: Principal Investigator: Laurence BOUILLET, PhD, Internal Medicine - University Hospital Grenoble-Alpes

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2019
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): September 1, 2022

Study Registration Dates

• First Submitted: October 17, 2018
• First Submitted That Met QC Criteria: December 26, 2018
• First Posted (Actual): December 28, 2018

Study Record Updates

• Last Update Posted (Actual): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 27, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Chronic Urticaria; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Histamine H1 Antagonists, Non-Sedating; Tranexamic Acid; Cetirizine; Levocetirizine
• Other Study ID Numbers: TACUS- 38RC18.103

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No