North American Study of Epistaxis in HHT (NOSE)
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- James Gossage
- Enrollment
- 123
- Locations
- 6
- Primary Endpoint
- Frequency of Epistaxis
Overview
Brief 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.
Detailed Description
140 patients with moderate to severe epistaxis secondary to HHT will be randomized to receive one of four intranasal sprays for a period of 12 weeks and then followed for an additional 12 weeks off therapy. Enrollment will occur over a period of 18-36 months. The primary endpoint will be the frequency of epistaxis. Secondary endpoints will include duration of epistaxis, the Hoag Epistaxis Severity Score (ESS), a quality of life survey, satisfaction with treatment, hemoglobin and ferritin levels, transfusion requirements, and treatment failure. The sprays will be: saline spray (Placebo); estriol 0.1% in methylcellulose suspension (EST); tranexamic acid 10% in saline (TA), and bevacizumab 1% in saline (BEV). All sprays will be applied to the nasal mucosa by an identical spray bottle at a dose of 0.1 ml per nostril twice daily (total dose of 0.4 ml daily). Thus, the delivered doses will be: EST, 0.4 mg/day; TA, 40 mg/day; BEV, 4 mg/day.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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:
- •Spontaneous and recurrent epistaxis.
- •Multiple telangiectasias at characteristic sites (lips, oral cavity, fingers, nose).
- •Visceral lesions such as gastrointestinal telangiectasias and arteriovenous malformations (AVM) in lung, brain, spine and liver.
- •A history of definite HHT in a first degree relative using these same criteria.
- •Epistaxis of at least 1 minute (on average) and which occurs at least once weekly when averaged during the preceding 8 weeks.
- •Epistaxis severity score (ESS) of at least 3.
- •Age of at least 18 years.
- •Written and informed consent obtained prior to study entry.
- •Subject is able and willing to return for outpatient visits.
Exclusion Criteria
- •Allergy to any of the active treatment agents or their spray additives.
- •Estimated life expectancy less than 1 year.
- •A psychiatric or substance abuse problem that is expected to interfere with study compliance.
- •History of deep venous thrombosis (DVT), pulmonary embolism (PE), acute myocardial infarction (MI), arterial thromboembolism, or ischemic stroke in the past 6 months.
- •History of receiving more than 12 units of red blood cells in the past 12 weeks.
- •Presence of an untreated coagulopathy that is felt to be contributing to the
- •History of estrogen receptor positive breast cancer. epistaxis.
- •Presence of active disseminated intravascular coagulation.
- •Uncontrolled hypertension (systolic BP \>160 and/or diastolic BP \>100).
- •Presence of untreated brain AVM.
Arms & Interventions
Placebo spray
sterile saline
Intervention: Sterile saline (Drug)
Bevacizumab spray
bevacizumab 1%
Intervention: Bevacizumab (Drug)
Estriol spray
Estriol 0.1%
Intervention: Estriol (Drug)
Tranexamic acid spray
tranexamic acid 10%
Intervention: Tranexamic Acid (Drug)
Outcomes
Primary Outcomes
Frequency of Epistaxis
Time Frame: Weeks 5-12 of active treatment phase
Bleeding episodes per week
Secondary Outcomes
- Hoag Epistaxis Severity Score(12 weeks)
- Duration of Epistaxis(5-12 weeks of active treatment)
- Hemoglobin Level(12 weeks)
- Number of Participants Requiring Red Blood Cell (RBC) Transfusion(12 weeks)
- Number of Participants With Treatment Failure(Baseline through 12 weeks)
Investigators
James Gossage
Director of Pulmonary Vascular Diseases and HHT
Augusta University