North American Study of Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)

NCT01408030 | Completed Phase 2 Results DMC

• 1 other identifier: GHSU 1008041
• Study Type: interventional
• Target: 123
• Locations: 1 country
• Sites: 6

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.

Conditions

Telangiectasia, Hereditary Hemorrhagic; Epistaxis

Keywords

epistaxis; HHT; bevacizumab; tranexamic acid; nosebleed; estrogen

Outcome Measures

Primary Outcomes (1)

• Frequency of Epistaxis

  Bleeding episodes per week

  Weeks 5-12 of active treatment phase

Secondary Outcomes (5)

• Duration of Epistaxis

  5-12 weeks of active treatment

• Hoag Epistaxis Severity Score

  12 weeks

• 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

Study Arms (4)

Placebo spray

PLACEBO COMPARATOR

sterile saline

Drug: Sterile saline

Bevacizumab spray

ACTIVE COMPARATOR

bevacizumab 1%

Drug: Bevacizumab

Estriol spray

ACTIVE COMPARATOR

Estriol 0.1%

Drug: Estriol

Tranexamic acid spray

ACTIVE COMPARATOR

tranexamic acid 10%

Drug: Tranexamic Acid

Interventions

Sterile saline DRUG

0.9%, 0.1 ml spray in each nostril bid

Also known as: Saline

Placebo spray

Bevacizumab DRUG

1% solution in saline, 0.1 ml spray in each nostril bid

Also known as: Avastin, Vascular endothelial growth factor (VEGF) inhibitor

Bevacizumab spray

Estriol DRUG

0.1% suspension in methylcellulose, 0.1 ml spray in each nostril bid

Also known as: Estrogen

Estriol spray

Tranexamic Acid DRUG

10% solution in saline, 0.1 ml spray in each nostril bid

Also known as: Lysteda

Tranexamic acid spray

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 3.0.
• 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.
• 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).
• Negative pregnancy test at enrollment.

You may not qualify if:

• 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.6. 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 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.
• \. 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.
• \. Addition of new treatments for epistaxis in the past 12 weeks (including laser ablation of nasal telangiectasias and over the counter medications).
• \. Presence of another overt cause (e.g. overt gastrointestinal bleeding) that is felt to be significantly contributing to anemia.
• \. Lactating women.

Sponsors & Collaborators

• James Gossage: lead
• HHT Foundation International: collaborator

Study Sites (6)

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Georgia Regents University

Augusta, Georgia, 30912, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (1)

• Whitehead KJ, Sautter NB, McWilliams JP, Chakinala MM, Merlo CA, Johnson MH, James M, Everett EM, Clancy MS, Faughnan ME, Oh SP, Olitsky SE, Pyeritz RE, Gossage JR. Effect of Topical Intranasal Therapy on Epistaxis Frequency in Patients With Hereditary Hemorrhagic Telangiectasia: A Randomized Clinical Trial. JAMA. 2016 Sep 6;316(9):943-51. doi: 10.1001/jama.2016.11724.

  PMID: 27599329 DERIVED

Related Links

• HHT Foundation website

MeSH Terms

Conditions

Telangiectasia, Hereditary Hemorrhagic; Epistaxis

Interventions

Sodium Chloride; Bevacizumab; Vascular Endothelial Growth Factor A; Estriol; Estrogens; Tranexamic Acid

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Telangiectasis; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Vascular Malformations; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Respiratory; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Vascular Endothelial Growth Factors; Angiogenic Proteins; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Limitations and Caveats

1\. One key limitation is the lack of a baseline epistaxis diary. 2. Drug absorption may have been hampered because of local scab and crust formation causing a barrier to drug penetration. 3. Saline may not be a true placebo due to hydration effects.

Results Point of Contact

• Title: James R. Gossage, MD, Medical Director of Cure HHT
• Organization: Cure HHT

jgossage@augusta.edu

706-721-6789

Study Officials

• James R Gossage, MD

  Augusta University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Pulmonary Vascular Diseases and HHT

Study Record Dates

• First Submitted: August 1, 2011
• First Posted: August 2, 2011
• Study Start: August 1, 2011
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: October 19, 2018
• Results First Posted: October 19, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)