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North American Study of Epistaxis in HHT (NOSE)

This study has been completed.
Sponsor:
Collaborator:
Hereditary Hemorrhagic Telangiectasia Foundation International
Information provided by (Responsible Party):
James Gossage, Georgia Regents University
ClinicalTrials.gov Identifier:
NCT01408030
First received: August 1, 2011
Last updated: November 5, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Telangiectasia, Hereditary Hemorrhagic
Epistaxis
Drug: Sterile saline
Drug: Bevacizumab
Drug: Estriol
Drug: Tranexamic Acid
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: North American Study of Epistaxis in HHT (NOSE)

Resource links provided by NLM:


Further study details as provided by Georgia Regents University:

Primary Outcome Measures:
  • Frequency of epistaxis [ Time Frame: Weeks 5-12 of active treatment phase ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of epistaxis [ Time Frame: 5-12 weeks of active treatment ] [ Designated as safety issue: No ]
  • Hoag Epistaxis Severity Score [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
  • Short Form-36 Health Survey [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
  • Supplemental Epistaxis Questionnaire [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
  • Hemoglobin level and ferritin levels [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
  • Units of RBC transfused [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
  • Treatment failure [ Time Frame: Baseline through 24 weeks ] [ Designated as safety issue: Yes ]
    Need for nasal surgery or severe complications such as acute MI, venous thromboembolism, or CNS hemorrhage


Enrollment: 121
Study Start Date: August 2011
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo spray Drug: Sterile saline
0.9%, 0.1 ml spray in each nostril bid
Other Name: Saline
Active Comparator: Bevacizumab spray Drug: Bevacizumab
1% solution in saline, 0.1 ml spray in each nostril bid
Other Names:
  • Avastin
  • VEGF inhibitor
Active Comparator: Estriol spray Drug: Estriol
0.1% suspension in methylcellulose, 0.1 ml spray in each nostril bid
Other Name: Estrogen
Active Comparator: Tranexamic acid spray Drug: Tranexamic Acid
10% solution in saline, 0.1 ml spray in each nostril bid
Other Name: Lysteda

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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, ALK-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.
  5. History of estrogen receptor positive breast cancer.
  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 epistaxis.
  8. Presence of active disseminated intravascular coagulation.
  9. Uncontrolled hypertension (SBP >160 and/or DBP >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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01408030

Locations
United States, California
University of California Los Angeles
Los Angeles, California, United States, 90095
United States, Georgia
Georgia Regents University
Augusta, Georgia, United States, 30912
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21205
United States, Missouri
Washington University School of Medicine
St Louis, Missouri, United States, 63110
United States, Oregon
Oregon Health Sciences University
Portland, Oregon, United States, 97239
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
James Gossage
Hereditary Hemorrhagic Telangiectasia Foundation International
Investigators
Principal Investigator: James R Gossage, MD Georgia Regents University
  More Information

Additional Information:
No publications provided

Responsible Party: James Gossage, Director of Pulmonary Vascular Diseases and HHT, Georgia Regents University
ClinicalTrials.gov Identifier: NCT01408030     History of Changes
Other Study ID Numbers: GHSU 1008041
Study First Received: August 1, 2011
Last Updated: November 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Georgia Regents University:
epistaxis
HHT
bevacizumab
tranexamic acid
nosebleed
estrogen

Additional relevant MeSH terms:
Epistaxis
Telangiectasia, Hereditary Hemorrhagic
Telangiectasis
Cardiovascular Abnormalities
Cardiovascular Diseases
Congenital Abnormalities
Hematologic Diseases
Hemorrhage
Hemorrhagic Disorders
Hemostatic Disorders
Nose Diseases
Otorhinolaryngologic Diseases
Pathologic Processes
Respiratory Tract Diseases
Vascular Diseases
Vascular Malformations
Bevacizumab
Estrogens
Tranexamic Acid
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antifibrinolytic Agents
Antineoplastic Agents
Coagulants
Fibrin Modulating Agents
Growth Inhibitors
Growth Substances
Hematologic Agents
Hemostatics
Hormones

ClinicalTrials.gov processed this record on November 20, 2014