ATERO : A Randomised Study With Tranexamic Acid in Epistaxis of Rendu Osler Syndrome

Telangiectasia, Hereditary Hemorrhagic Clinical Trial

Official title: ATERO : A Randomised Study With Tranexamic Acid in Epistaxis of Rendu Osler Syndrome. Beneficial or Iatrogenic Effects.

Status Completed

Clinical Trial Summary

Scientific Objectives Primary objective : Demonstrate that oral intake of tranexamic acid significantly reduces the risk of epistaxis occurrence, estimated by the average monthly duration of episodes of epistaxis.

Secondary objectives :

• Document the benefit of tranexamic acid on the amount of haemoglobine and quality of life of patients.

• Identify scalable and genetic factors of response to the treatment by tranexamic acid.

• Describe compliance and tolerance of the treatment. Method Experimental Design We suggest the realisation of a randomised comparative clinical trial versus placebo, with a crossover of random alternated periods of three months over a total of six months.

Study Population 213 affected patients, displaying sufficiently invalidating epistaxis to require a basal treatment, will be recruited and followed every 3 months. Recruitment will lean on teams who are part of the national French network in close collaboration with the reference centre for the Rendu-Osler disorder, appointed to Lyon on the 19th of November 2004. Follow up of the study will be carried out by the Clinical Investigational Centre of the related towns.

Outcome measures The main criterion of efficacy is the average duration of epistaxis, the secondary criterion of efficacy is the average number of epistaxis measured per month. Tolerance will be analysed according to the occurrence of venal or arterial thrombosis and allergic accidents. Venal thrombosis will systematically be sought by an inferior limbs echodoppler. Response markers will be sought through modelisation incorporating environmental, phenotypic and genetic factors.

Clinical Trial Description

Argumentation Rendu-Osler syndrome, rare but ubiquitary, affects at least 8000 persons in France. This genetic disorder is characterised by a dominant autosomal hereditary transmission of telangiectasis and arteriovenous fistulae. The most apparent expression of the disorder, often the cause of chronic anaemia, is the occurrence of spontaneous, repeated, frequent and sometimes abundant epistaxis to the extent that continuous martial treatment and multiple transfusions are necessary. The handling of this major symptom of the disorder is badly coded and often demands local ENT treatments or medication whose efficacy is not sufficiently documented. Among them, an anti-fibrinolytic, tranexamic acid, has been evaluated several times with a low level of proof, so that it is regularly prescribed with a good impression of efficacy for certain patients. It therefore seems essential that these prescriptions should be based on more reliable data thereby providing clearer information to patients regarding the expected benefits. The recent report of a high frequency of thrombophlebitis in RO patients and the ancient concept of coagulation disorders or thrombosis (Bick 1981) have lead to a restriction of the inclusion criteria and a systematic search for a possible iatrogenic effect (inferior limbs venous echodoppler).

Scientific Objectives Primary objective : Demonstrate that oral intake of tranexamic acid significantly reduces the risk of epistaxis occurrence, estimated by the average monthly duration of episodes of epistaxis.

Secondary objectives :

• Document the benefit of tranexamic acid on the amount of haemoglobine and quality of life of patients.

• Identify scalable and genetic factors of response to the treatment by tranexamic acid.

• Describe compliance and tolerance of the treatment. Method Experimental Design We suggest the realisation of a randomised comparative clinical trial versus placebo, with a crossover of random alternated periods of three months over a total of six months.

Study Population 213 affected patients, displaying sufficiently invalidating epistaxis to require a basal treatment, will be recruited and followed every 3 months. Recruitment will lean on teams who are part of the national French network in close collaboration with the reference centre for the Rendu-Osler disorder, appointed to Lyon on the 19th of November 2004. Follow up of the study will be carried out by the Clinical Investigational Centre of the related towns.

Outcome measures The main criterion of efficacy is the average duration of epistaxis, the secondary criterion of efficacy is the average number of epistaxis measured per month. Tolerance will be analysed according to the occurrence of venal or arterial thrombosis and allergic accidents. Venal thrombosis will systematically be sought by an inferior limbs echodoppler. Response markers will be sought through modelisation incorporating environmental, phenotypic and genetic factors.

Expected benefits From an individual point of view, the knowledge of the response to tranexamic acid measured the most precisely possible, represents a benefit for each study participant, who will be able to continue the treatment knowingly if it proves efficient. From a general point of view, the ATERO study will aid in the decision whether to continue this course of action which despite its lack of proof is justified by its efficacy as well as its cost and absence of adverse effects. The precise documentation of its innocuousness may be necessary by the means of a specific study depending on the results on the ATERO study. ;

Related Conditions & MeSH terms

• Epistaxis
• Osler-Rendu Disease
• Telangiectasia, Hereditary Hemorrhagic
• Telangiectasis

• NCT number: NCT00355108
• Study type: Interventional
• Source: Hospices Civils de Lyon
• Status: Completed
• Phase: Phase 3
• Start date: September 2006
• Completion date: May 2010