E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronique Spontaneous urticaria |
Urticaire chronique spontanée |
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E.1.1.1 | Medical condition in easily understood language |
Chronique Spontaneous urticaria |
Urticaire chronique spontanée |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate the efficacy and safety of levocetirizine 10mg / day + tranexamic acid 2g / day versus levocetirizine 20mg / day alone in the chronic treatment of chronic urticaria evaluated at 4 weeks. |
Evaluer l’efficacité et la tolérance de l’association lévocétirizine 10mg/j + acide tranexamique 2g/j versus lévocetirizine seule 20mg/j en traitement de fond de l’urticaire chronique évaluées à 4 semaines. |
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E.2.2 | Secondary objectives of the trial |
657/5000
1 Demonstrate non-inferiority of levocetirizine 10mg / day + tranexamic acid (AT) 2g versus levocetirizine alone 20mg / day in terms of efficacy on Angioedema activity score (AAS).
2. Demonstrate the superiority of the association in terms of efficacy evaluated by a combined AAS + UAS7 (Urticaria activity score ) criterion
3.Identify the clinical features of responders to the combination rather than antihistamines alone.
4. Estimate the prognostic value, in terms of discrimination and calibration, of D-dimer for preaching the UCS response to tranexamic acid / antihistamine association.
5.Compare the quality of life associated with each therapy. |
1 Démontrer la non infériorité de l’association lévocétirizine 10mg/j + acide tranexamique (AT) 2g versus lévocetirizine seule 20mg/j en terme d’efficacité sur l’AAS.
2.Démontrer la supériorité de l’association en termes d’efficacité évaluée par un critère combiné AAS + UAS7
3.Identifier les caractéristiques cliniques des patients répondeurs à l’association plutôt qu’aux anti-histaminiques seuls.
4.Estimer la valeur pronostique, en termes de discrimination et de calibration, des D-dimères pour la prédication de la réponse de l’UCS à l’association acide tranexamique/anti-histaminique.
5.Comparer la qualité de vie associée à chaque thérapeutique.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patient over 18 years old
- having 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 symptoms urticarial eruptions and / or recurrent angioedema for at least 6 weeks.
- having given his written consent
- affiliated to a social security scheme or beneficiary of such a scheme |
- Patient âgé de plus de 18 ans
- ayant une urticaire chronique spontanée, selon les critères de l’European Academy of Allergology and Clinical Immunology (EAACI) en accord avec l’European Dermatology Forum (EDF), et la World Allergy Organization (WAO), correspondant à une association des symptômes suivants: éruptions urticariennes et/ou angioedèmes récidivants depuis au moins 6 semaines.
- ayant donné son consentement écrit
- affilié(e) à un régime de sécurité sociale ou bénéficiaire d’un tel régime
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E.4 | Principal exclusion criteria |
- Urticaria associated with a specific systemic disease including cutaneous and systemic mastocytosis, urticarial vasculitis, autoinflammatory diseases associated with cryopyrin
- Bradykinetic angioedema and isolated angioedema whose origin is not clearly attributable to spontaneous chronic urticaria.
- Presence of a contraindication to tranexamic acid: history of venous thromboembolic accident (deep vein thrombosis, pulmonary embolism) or arterial thromboembolic stroke (angina, myocardial infarction, stroke); fibrinolytic states reactive to consumption coagulopathy; severe renal failure; antecedent of convulsions.
- Presence of a contraindication to levocetirizine: known hypersensitivity to any of the components of the product, or to piperazine derivatives; severe renal insufficiency with creatinine clearance less than 10 ml / min. History of congenital galactosemia, glucose-galactose malabsorption syndrome or lactase deficiency (presence of lactose in the tablet).
- Subject treated or having been treated with oral corticosteroids in the month preceding the selection
- Topic treated or treated by Montelukast in the week before the selection
- Subject treated or having been treated with H2 blockers in the week preceding the selection
- Subject receiving anticoagulant or antiaggregant.
- Subject treated or having been treated with immunosuppressants (eg methotrexate, ciclosporin, azathioprine, mycophenolate mofetil ...) in the month preceding the selection
- Persons referred to in Articles L1121-5 to L1121-8 of the CSP (pregnant woman, parturient, mother who is breastfeeding, person deprived of liberty by judicial or administrative decision, person subject to a measure of legal protection, can not to be included in clinical trials)
- Subject in exclusion period of another study
- Subject can not be contacted in case of emergency |
- Urticaires associées à une maladie de système spécifique incluant les mastocytoses cutanées et systémiques, les vascularites urticariennes, les maladies autoinflammatoires associées à la cryopyrine
- Angioedèmes bradykiniques et angioedèmes isolés dont l’origine n’est pas clairement attribuable à une urticaire chronique spontanée.
- Présence d’une contre-indication à l’acide tranexamique : antécédents d'accident thrombo-embolique veineux (thrombose veineuse profonde, embolie pulmonaire) ou d'accident thrombo-embolique artériel (angor, infarctus du myocarde, accident vasculaire cérébral); états fibrinolytiques réactionnels à une coagulopathie de consommation; insuffisance rénale grave ; antécédent de convulsions.
- Présence d’une contre-indication à la lévocétirizine : hypersensibilité connue à l'un des composants du produit, ou aux dérivés de la pipérazine ; insuffisance rénale sévère avec clairance de la créatinine inférieure à 10 ml/min. Antécédent de galactosémie congénitale, de syndrome de malabsorption du glucose et du galactose ou de déficit en lactase (présence de lactose dans le comprimé).
- Sujet traité ou ayant été traité par corticoïdes oraux dans le mois précédant la sélection
- Sujet traité ou ayant été traité par Montelukast dans la semaine précédant la sélection
- Sujet traité ou ayant été traité par anti-H2 dans la semaine précédant la sélection
- Sujet recevant un anticoagulant ou un antiagrégant.
- Sujet traité ou ayant été traité par immunosuppresseurs (ex : methotrexate, ciclosporine, azathioprine, mycophenolate mofetil…) dans le mois précédant la sélection
- Personnes visées aux articles L1121-5 à L1121-8 du CSP (femme enceinte, parturiente, mère qui allaite, personne privée de liberté par décision judiciaire ou administrative, personne faisant l’objet d’une mesure de protection légale, ne peuvent pas être inclues dans les essais cliniques)
- Sujet en période d’exclusion d’une autre étude
- Sujet ne pouvant être contacté en cas d’urgence |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Evolution of the UAS7 score between the beginning (J0) and the end (J28) of the treatment period. The analysis will be conducted per protocol and intention to treat and non-inferiority will be retained if both analyzes are convergent (Le Henanff, A. et al., JAMA 2006; 295: 1147-1151). Then, a hierarchical analysis on the intention-to-treat population will be carried out with a superiority test only if non-inferiority is retained in per protocol analysis.
2. Collection of adverse effects
3. Evolution of the UAS7 score between the beginning (D0) and the end (D28) of the treatment period
1. Evolution of the UAS7 score between the beginning (J0) and the end (J28) of the treatment period. The analysis will be conducted per protocol and intention to treat and non-inferiority will be retained if both analyzes are convergent (Le Henanff, A. et al., JAMA 2006; 295: 1147-1151). Then, a hierarchical analysis on the intention-to-treat population will be carried out with a superiority test only if non-inferiority is retained in per protocol analysis.
2. Collection of adverse effects
3. Evolution of the UAS7 score between the beginning (D0) and the end (D28) of the treatment period
1. Evolution of the UAS7 score between the beginning (J0) and the end (J28) of the treatment period. The analysis will be conducted per protocol and intention to treat and non-inferiority will be retained if both analyzes are convergent (Le Henanff, A. et al., JAMA 2006; 295: 1147-1151). Then, a hierarchical analysis on the intention-to-treat population will be carried out with a superiority test only if non-inferiority is retained in per protocol analysis.
2. Collection of adverse effects
3. Evolution of the UAS7 score between the beginning (D0) and the end (D28) of the treatment period
1. Evolution of the UAS7 score between the beginning (J0) and the end (J28) of the treatment period. The analysis will be convergent (Henanff, A. et al., JAMA 2006; 295: 1147-1151). Then, a hierarchical analysis on the intention-to-treat population will be carried out with a superiority test.
2. Collection of adverse effects
3. Evolution of the UAS7 score between the beginning (D0) and the end (D28) of the treatment period
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1. Evolution du score UAS7 entre le début (J0) et la fin (J28) de la période de traitement. L’analyse sera menée en per protocole et intention de traiter et la non infériorité sera retenue si les deux analyses sont convergentes (Le Henanff, A. et al. JAMA 2006;295:1147-1151). Ensuite, une analyse hiérarchique sur la population en intention de traiter sera réalisée avec un test de supériorité uniquement si la non infériorité est retenue en analyse per protocole.
2. Recueil des effets indésirables
3. Evolution du score UAS7 entre le début (J0) et la fin (J28) de la période de traitement
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1.Evolution of the AAS score between the beginning (J0) and the end (J28) of the treatment period.
2. Combined improvement criterion of at least 50% of the UAS7 clinical score and the AAS score. These are 2 activity scores validated by the latest EAACI consensus:
- UAS7 score: score assessing pruritus and number of urticaria plaques
- AAS score: score evaluating the activity of seizures
3. Differences in the clinical profiles of the responders to each of the therapies.
4. Area under the ROC curve and D-dimer calibration for the prediction of therapeutic response to tranexamic acid.
5. Improvement of the quality of life, evaluated by the 2 scores validated during the last international consensus:
- CU-Q2oL score: assessing the impact of urticaria attacks
- AE-QoL score: assessing the impact of episodes of angioedema associated with chronic urticaria
1.Evolution of the AAS score between the beginning (J0) and the end (J28) of the treatment period.
2. Combined improvement criterion of at least 50% of the UAS7 clinical score and the AAS score. These are 2 activity scores validated by the latest EAACI consensus:
- UAS7 score: score assessing pruritus and number of urticaria plaques
- AAS score: score evaluating the activity of seizures
3. Differences in the clinical profiles of the responders to each of the therapies.
4. Area under the ROC curve and D-dimer calibration for the prediction of therapeutic response to tranexamic acid.
5. Improvement of the quality of life, evaluated by the 2 scores validated during the last international consensus:
- CU-Q2oL score: assessing the impact of urticaria attacks
- AE-QoL score: assessing the impact of episodes of angioedema associated with chronic urticaria
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1.Evolution du score AAS entre le début (J0) et la fin (J28) de la période de traitement.
2.Critère combiné d’amélioration d’au moins 50% du score clinique UAS7 et du score AAS. Il s’agit de 2 scores d’activité validés par le dernier consensus de l’EAACI :
- score UAS7 : score évaluant le prurit et le nombre de plaques d’urticaire
- score AAS : score évaluant l’activité des crises
3. Différences dans les profils cliniques des patients répondeurs à chacune des thérapeutiques.
4. Aire sous la courbe ROC et calibration des D-dimères pour la prédiction de la réponse thérapeutique à l’acide tranexamique.
5. Amélioration de la qualité de vie, évaluée par les 2 scores validés lors du dernier consensus international :
- score CU-Q2oL : évaluant le retentissement lié aux crises d’urticaire
- score AE-QoL : évaluant le retentissement lié au aux épisodes d’angioedème associés à l’urticaire chronique
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of study is the last visit of last patient, 15 days after the end of his treatment. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |