Intranasal Submucosal Bevacizumab for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)

Study Overview
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Brief Summary
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In a case series intranasal submucosal bevacizumab has been shown to reduce epistaxis in patients suffering from Hereditary Haemorrhagic Telangiectasia together with KTP Laser therapy. The aim of this study is to evaluate the effectiveness of submucosal intranasal bevacizumab compared to placebo in a randomized double blind trial setting.

Official Title
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A Randomized Double Blind Placebo Controlled Trial of Intranasal Submucosal Bevacizumab in Hereditary Hemorrhagic Telangiectasia

Conditions
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HHT, Morbus Osler, Epistaxis

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: NaCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed and staged HHT (Shovlin et al 2000) Age 18-80 Minimum of 2 episodes of epistaxis/ week Ability and willingness to complete diary and comply with study requirements. Exclusion Criteria: Uncontrolled hypertension (systolic blood pressure > 150mmHg, diastolic blood pressure > 90mmHg) History of a thromboembolic event, including myocardial infarction or cerebral vascular accident Malignancy of the upper respiratory tract within the last year Recent (<3 months) or planned surgery Proteinuria Nasal intervention (Laser or Cautery) in pretreatment phase Allergy to local anesthetic

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bevacizumab<br>submucosal intranasal bevacizumab on day 0 | Drug: Bevacizumab<br>* 100mg intranasal submucosal bevacizumab in 10ml<br>|
| Placebo Comparator: placebo<br>0.9% NaCl intranasal submucosal on day 0 | Drug: NaCl<br>* 10ml of 0.9% NaCl intranasal submucosal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| relative change in average daily Epistaxis VAS scores compared to baseline | Daily epistaxis VAS scores are recorded in a diary. The baseline score is the average daily epistaxis VAS score 4 weeks before treatment (day -28 to 0). This score is compared to the average daily VAS score day 10-84 posttreatment. The relative change of this average score compared to baseline is the primary outcome. | day 10 - 84 posttreatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Epistaxis Severity Score HHT-ESS compared to baseline |  | 3 months post treatment | 
| Epistaxis frequency, duration and severity compared to baseline |  | day 10 - 84 posttreatment | 
| Number of emergency department visits due to epistaxis compared to baseline |  | day 10 - 84 posttreatment | 
| lab results (ferritin values, Hb, Hct) compared to baseline |  | day 84 posttreatment | 
| Number of transfusions needed compared to baseline |  | day 10-84 posttreatment | 
| Average daily epistaxis VAS scores compared to baseline among age groups and among groups with different epistaxis severity |  | day 10-84 posttreatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HHT, Epistaxis, Osler, Weber, Rendu, Hereditary haemorrhagic telangiectasia