ATERO : A Randomised Study With Tranexamic Acid in Epistaxis of Rendu Osler Syndrome
Condition: Telangiectasia, Hereditary Hemorrhagic; Osler-Rendu Disease
MeSH terms: Epistaxis; Telangiectasis; Telangiectasia, Hereditary Hemorrhagic
Study type: Interventional
Phase: Phase 3

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.
    

Detailed 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.
    

Intervention name(s): tranexamic acid
Intervention type(s): Drug
Intervention description(s): 2 3-month-periods in cross-over: placebo or 3g/day of tranexamic acid
Intervention MeSH terms: Tranexamic Acid
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Rendu Osler syndrome; Epistaxis; Tranexamic acid; clinical trial