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

May 23, 2019 updated by: Hospices Civils de Lyon

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

170

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Lyon, France, 69002
        • Henri PLAUCHU

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Repeated, spontaneous epistaxis in a known Rendu Osler patient who wants global caring, these must be daily epistaxis (> 28 a month) or a total amount of 60 minutes of bleeding a month (50 % Rendu-Osler patients bleed before 20 and 99 % at 50 when penetrance is complete).
  • Good completion of the grid of control by recording the number and duration of epistaxis over a period of three month.

Exclusion Criteria:

  • Rendu Osler syndrome with specific phenotype : absence of epistaxis or occasional epistaxis, no need for particular care.
  • Maintained expectations of an ENT treatment of epistaxis in a delay of three months.
  • Incapacity of detailing the number of epistaxis, especially, at least, within three months before entering the study.
  • No informed consent obtained after informing the patient on his participation to the study.
  • Expected lack of observance because of an incapacity to compel to the daily treatment.
  • Formal indication to Tranexamic Acid (angioneurotic oedema as a disease modifying treatment of 3 to 4 g/ day).
  • Contra-indications to Tranexamic acid: history of convulsion, arterial or veinous thrombosis, , positivity of veinous echo doppler of the inferior limbs; Serum creatinine > 250 µmol/l.

N.B. Cases of bad observance are not frequent, patients being highly concerned with a treatment to reduce their discomfort and anaemia. They are more likely ready to move to a centre insuring this handling. Nevertheless, lack of observance will be detected over a period of 15 days of placebo in simple blind, before randomization.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary efficacy criterion is the average monthly duration of epistaxis.
Time Frame: after first 3 month period treatment or placebo and after second 3 month period treatment or placebo
after first 3 month period treatment or placebo and after second 3 month period treatment or placebo

Secondary Outcome Measures

Outcome Measure
Time Frame
the average monthly number of epistaxis,
Time Frame: after first 3 month period treatment or placebo and after second 3 month period treatment or placebo
after first 3 month period treatment or placebo and after second 3 month period treatment or placebo
the average duration of one episode of epistaxis measured over a month,
Time Frame: after first 3 month period treatment or placebo and after second 3 month period treatment or placebo
after first 3 month period treatment or placebo and after second 3 month period treatment or placebo
the Haemoglobin level
Time Frame: after first 3 month period treatment or placebo and after second 3 month period treatment or placebo
after first 3 month period treatment or placebo and after second 3 month period treatment or placebo
estimation of Quality of life.
Time Frame: over first 3 month period treatment or placebo and over second 3 month period treatment or placebo
over first 3 month period treatment or placebo and over second 3 month period treatment or placebo
Outcome of following Adverse Event: arterial or veinous thrombosis, allergic accident
Time Frame: during first 3 month period treatment or placebo and over second 3 month period treatment or placebo
during first 3 month period treatment or placebo and over second 3 month period treatment or placebo

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospices Civils de Lyon

Investigators

  • Principal Investigator: Henri PLAUCHU, MD, Hospices Civils de Lyon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion (Actual)

May 1, 2010

Study Completion (Actual)

May 1, 2010

Study Registration Dates

First Submitted

July 20, 2006

First Submitted That Met QC Criteria

July 20, 2006

First Posted (Estimate)

July 21, 2006

Study Record Updates

Last Update Posted (Actual)

May 28, 2019

Last Update Submitted That Met QC Criteria

May 23, 2019

Last Verified

December 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2005.405

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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