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Trial record 56 of 466 for:    Inherited Bleeding Disorder

Propranolol for Epistaxis in Hereditary Hemorrhagic Telangiectasia Patients (EPERO)

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ClinicalTrials.gov Identifier: NCT04113187
Recruitment Status : Not yet recruiting
First Posted : October 2, 2019
Last Update Posted : October 2, 2019
Sponsor:
Collaborator:
AMRO-HHT-France - Association Maladie de Rendu-Osler
Information provided by (Responsible Party):
University Hospital, Bordeaux

Brief Summary:
Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder of angiogenesis associated with disabling epistaxis. Management of these nose bleedings requires more effective treatment. Propranolol, a beta-blocker, is a potentially useful therapeutic considering its anti-angiogenic properties. Our objective is to explore the efficacy of propranolol, three months after its introduction, on the cumulative duration of epistaxis in HHT patients.

Condition or disease Intervention/treatment Phase
Hereditary Hemorrhagic Telangiectasia Osler Weber Rendu Disease Drug: Propranolol treatment Drug: Placebo Phase 3

Detailed Description:

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare systemic autosomal dominantly inherited disorder of angiogenesis. Its major feature is the occurrence in 90% of patients of spontaneous and recurrent epistaxis responsible for iron deficiency and chronic anemia. Various conservative and interventional treatments have been described for these conditions, but no optimal therapy exists. Inhibiting angiogenesis process is an interesting therapeutic option. Propranolol, a non-cardio-selective beta-blocker, could represent a new candidate for the therapy of HHT telangiectasia as it suppresses angiogenesis in vitro. This anti-angiogenic property is well-known in pediatric dermatology, since C. Léauté-Labrèze and al. have demonstrated a great improvement of infantile hemangioma undergoing propranolol treatment. At the University Hospital Center of Bordeaux, the investigators assessed in a preliminary study the efficacy of propranolol for HHT epistaxis. Nine of ten patients receiving propranolol for cardiologic or neurologic indications, retrospectively analyzed, significantly improved their Epistaxis Severity Score. Ten patients were then prospectively included and after 3 months of propranolol treatment, the median duration of epistaxis per month significantly decreased (p=0,007) as well as the number of epistaxis episodes per month (p=0,015).

To confirm these results, the investigators would like to study the efficacy of propranolol given per os at the dose of 40 mg twice a day for a three-months period, in comparison to a placebo. Throughout the study, patients will complete specific grids recording the number of epistaxis episodes per month and the cumulative duration of nose bleedings. A follow-up of 6 months will be done (4 visits after inclusion), recording clinical and biological data and monitoring the tolerance of treatment.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 38 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Study of the Efficacy of Propranolol for the Management of Epistaxis in Hereditary Hemorrhagic Telangiectasia Patients
Estimated Study Start Date : December 2019
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
Experimental: Propranolol arm Drug: Propranolol treatment
40 mg twice a day (morning and evening), per os, during three months

Placebo Comparator: Placebo arm Drug: Placebo
per os, twice a day (morning and evening) during three months




Primary Outcome Measures :
  1. Cumulative duration of epistaxis (in minutes) [ Time Frame: 6 months after baseline (Day 0) ]

Secondary Outcome Measures :
  1. Frequency of epistaxis (number of episodes) per month [ Time Frame: At baseline (Day 0), 3 months and 6 months after baseline ]
  2. Number of cutaneous telangiectasia on hands and face [ Time Frame: At baseline (Day 0), 3 months and 6 months after baseline. ]
  3. Levels of hemoglobin [ Time Frame: At baseline (Day 0), 3 months and 6 months after baseline. ]
  4. Levels of ferritin [ Time Frame: At baseline (Day 0), 3 months and 6 months after baseline. ]
  5. Number of red blood cells transfusions [ Time Frame: At baseline (Day 0), 3 months and 6 months after baseline. ]
  6. Short Form (SF) 36 Health Survey [ Time Frame: At baseline (Day 0), 3 months and 6 months after baseline. ]
  7. Number of adverse events [ Time Frame: 3 months and 6 months after baseline (Day 0). ]
  8. Measurement of blood pressure [ Time Frame: At baseline (Day 0), 1 month, 3 months and 6 months after baseline. ]
  9. Measurement of heart rate [ Time Frame: At baseline (Day 0), 1 month, 3 months and 6 months after baseline. ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years
  • Confirmed diagnosis of HHT : 3 or more Curaçao criteria (spontaneous and recurrent epistaxis; multiple telangiectasia at characteristic sites; visceral lesions such as gastrointestinal telangiectasia or arteriovenous malformations; family history: a first degree relative with HHT according to these criteria ) or mutations of genes encoding for ALK1, ENG or SMAD4
  • Patient suffering from recurrent epistaxis (more than a mean of 10 episodes/month) and/or with a cumulative mean duration per month more than 20 minutes, according to specific grids completed at least three months before inclusion.
  • Patient insured under the French social security system
  • Free and informed consent signed by investigator and patient

Exclusion Criteria:

  • Pregnancy or breast-feeding
  • Incomplete epistaxis grids in the month prior inclusion
  • Current beta-blocker treatment
  • Hypersensitivity to the active substance or excipient
  • Patients with type I or type II diabetes, treated with insulin, sulphonylureas or meglitinides
  • Patients with heart failure
  • Patients with liver failure
  • Patients with hepatic arteriovenous malformations responsible for high-output cardiac failure or severe hepatic dysfunction
  • Patients with severe psoriasis (PASI>10)
  • Contra-indication to beta-blocker treatment : asthma, chronic obstructive bronchopneumopathy, atrioventricular block of second or third degrees without pacemaker, Prinzmetal's angina, bradycardia < 50bpm, Raynaud's phenomenon, oblitering arteriopathy of the lower limbs, low blood pressure, non-treated pheochromocytoma
  • Participation in another clinical therapeutic trial less than 3 months before inclusion
  • Protected adult according to french law

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04113187


Contacts
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Contact: Anne CONTIS, MD (0)556795828 ext +33 anne.contis@chu-bordeaux.fr
Contact: Valérie AURILLAC (0)556795720 ext +33 valerie.aurillac@chu-bordeaux.fr

Locations
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France
CHU de Bordeaux - service de médecine interne Not yet recruiting
Bordeaux, France
Contact: Anne CONTIS, MD         
Principal Investigator: Anne CONTIS, MD         
Sub-Investigator: Pierre DUFFAU, Prof         
Sponsors and Collaborators
University Hospital, Bordeaux
AMRO-HHT-France - Association Maladie de Rendu-Osler
Investigators
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Principal Investigator: Anne CONTIS, MD University Hospital, Bordeaux
Study Chair: Antoine BENARD, MD, PhD University Hospital, Bordeaux

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Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT04113187     History of Changes
Other Study ID Numbers: CHUBX 2015/32
First Posted: October 2, 2019    Key Record Dates
Last Update Posted: October 2, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Bordeaux:
angiogenesis
epistaxis
propranolol
Additional relevant MeSH terms:
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Telangiectasia, Hereditary Hemorrhagic
Vascular Diseases
Cardiovascular Diseases
Nose Diseases
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Hemorrhage
Hemostatic Disorders
Hemorrhagic Disorders
Hematologic Diseases
Epistaxis
Telangiectasis
Pathologic Processes
Signs and Symptoms, Respiratory
Signs and Symptoms
Vascular Malformations
Cardiovascular Abnormalities
Congenital Abnormalities
Propranolol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents