North American Study of Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)
Condition: Telangiectasia, Hereditary Hemorrhagic; Epistaxis
MeSH terms: Epistaxis; Telangiectasis; Telangiectasia, Hereditary Hemorrhagic
Intervention: Sterile saline; Bevacizumab; Estriol; Tranexamic Acid
Intervention description: 0.9%, 0.1 ml spray in each nostril bid; 1% solution in saline, 0.1 ml spray in each nostril bid; 0.1% suspension in methylcellulose, 0.1 ml spray in each nostril bid; 10% solution in saline, 0.1 ml spray in each nostril bid
Intervention MeSH terms: Bevacizumab; Tranexamic Acid; Endothelial Growth Factors; Estrogens
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 123.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: epistaxis; HHT; bevacizumab; tranexamic acid; nosebleed; estrogen

Summary:

      The purpose of the NOSE Study is to carefully examine the efficacy and safety of 3 nasal
      sprays (bevacizumab, estriol, and tranexamic acid), compared to placebo, for the treatment of
      HHT related nosebleeds.
    

Eligibility criteria:

        Inclusion Criteria:

          1. A diagnosis of definite or possible HHT by the Curacao criteria (Shovlin 2000) or a
             positive DNA test for HHT (as characterized by a disease causing mutation in the gene
             coding for endoglin, activin like kinase 1, or SMAD-4). According to the Curacao
             criteria, a definite diagnosis of HHT is defined as having at least 3 of the following
             criteria while a possible diagnosis is defined as 2 criteria:

               1. Spontaneous and recurrent epistaxis.

               2. Multiple telangiectasias at characteristic sites (lips, oral cavity, fingers,
                  nose).

               3. Visceral lesions such as gastrointestinal telangiectasias and arteriovenous
                  malformations (AVM) in lung, brain, spine and liver.

               4. A history of definite HHT in a first degree relative using these same criteria.

          2. Epistaxis of at least 1 minute (on average) and which occurs at least once weekly when
             averaged during the preceding 8 weeks.

          3. Epistaxis severity score (ESS) of at least 3.0.

          4. Age of at least 18 years.

          5. Written and informed consent obtained prior to study entry.

          6. Subject is able and willing to return for outpatient visits.

          7. The epistaxis is considered to be clinically stable during the past 8 weeks in the
             clinical judgment of the investigator (i.e. no major changes in frequency or duration
             of epistaxis or in transfusion requirements).

          8. Negative pregnancy test at enrollment.

        Exclusion Criteria:

          1. Allergy to any of the active treatment agents or their spray additives.

          2. Estimated life expectancy less than 1 year.

          3. A psychiatric or substance abuse problem that is expected to interfere with study
             compliance.

          4. History of deep venous thrombosis (DVT), pulmonary embolism (PE), acute myocardial
             infarction (MI), arterial thromboembolism, or ischemic stroke in the past 6 months.6.
             History of receiving more than 12 units of red blood cells in the past 12 weeks.

        7. Presence of an untreated coagulopathy that is felt to be contributing to the 5. History
        of estrogen receptor positive breast cancer. epistaxis. 8. Presence of active disseminated
        intravascular coagulation. 9. Uncontrolled hypertension (systolic BP >160 and/or diastolic
        BP >100). 10. Presence of untreated brain AVM. 11. Presence of active malignancy in the
        brain, lung, or colon. 12. Presence of symptomatic heart failure. 13. Use of estrogens,
        epsilon aminocaproic acid, tranexamic acid, or thalidomide by any route for more than 1
        week in the past 12 weeks. Any use of a VEGF inhibitor by any route in the past 24 weeks.

        14. Baseline use of the following anticoagulants is not allowed: warfarin or other vitamin
        K antagonists at any dose; unfractionated or low molecular weight heparins at standard
        doses for treatment of venous thromboembolism (VTE); or aspirin at >325 mg/day. Baseline
        use of the following anticoagulants is allowed: heparins at standard doses for VTE
        prophylaxis; clopidogrel; or aspirin at ≤325 mg/day.

        15. Addition of new treatments for epistaxis in the past 12 weeks (including laser ablation
        of nasal telangiectasias and over the counter medications).

        16. Presence of another overt cause (e.g. overt gastrointestinal bleeding) that is felt to
        be significantly contributing to anemia.

        17. Lactating women.