search
Back to results

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

Primary Purpose

Telangiectasia, Hereditary Hemorrhagic, Osler-Rendu Disease

Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
tranexamic acid
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Telangiectasia, Hereditary Hemorrhagic focused on measuring Rendu Osler syndrome, Epistaxis, Tranexamic acid, clinical trial

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Henri PLAUCHU

Outcomes

Primary Outcome Measures

The primary efficacy criterion is the average monthly duration of epistaxis.

Secondary Outcome Measures

the average monthly number of epistaxis,
the average duration of one episode of epistaxis measured over a month,
the Haemoglobin level
estimation of Quality of life.
Outcome of following Adverse Event: arterial or veinous thrombosis, allergic accident

Full Information

First Posted
July 20, 2006
Last Updated
May 23, 2019
Sponsor
Hospices Civils de Lyon
search

1. Study Identification

Unique Protocol Identification Number
NCT00355108
Brief Title
ATERO : A Randomised Study With Tranexamic Acid in Epistaxis of Rendu Osler Syndrome
Official Title
ATERO : A Randomised Study With Tranexamic Acid in Epistaxis of Rendu Osler Syndrome. Beneficial or Iatrogenic Effects.
Study Type
Interventional

2. Study Status

Record Verification Date
December 2010
Overall Recruitment Status
Completed
Study Start Date
September 2006 (undefined)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
May 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Hospices Civils de Lyon

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Telangiectasia, Hereditary Hemorrhagic, Osler-Rendu Disease
Keywords
Rendu Osler syndrome, Epistaxis, Tranexamic acid, clinical trial

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
170 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
tranexamic acid
Intervention Description
2 3-month-periods in cross-over: placebo or 3g/day of tranexamic acid
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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
Title
the Haemoglobin level
Time Frame
after first 3 month period treatment or placebo and after second 3 month period treatment or placebo
Title
estimation of Quality of life.
Time Frame
over first 3 month period treatment or placebo and over second 3 month period treatment or placebo
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Henri PLAUCHU, MD
Organizational Affiliation
Hospices Civils de Lyon
Official's Role
Principal Investigator
Facility Information:
Facility Name
Henri PLAUCHU
City
Lyon
ZIP/Postal Code
69002
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
25040799
Citation
Gaillard S, Dupuis-Girod S, Boutitie F, Riviere S, Moriniere S, Hatron PY, Manfredi G, Kaminsky P, Capitaine AL, Roy P, Gueyffier F, Plauchu H; ATERO Study Group. Tranexamic acid for epistaxis in hereditary hemorrhagic telangiectasia patients: a European cross-over controlled trial in a rare disease. J Thromb Haemost. 2014 Sep;12(9):1494-502. doi: 10.1111/jth.12654. Epub 2014 Jul 29.
Results Reference
result

Learn more about this trial

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

We'll reach out to this number within 24 hrs