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

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ClinicalTrials.gov Identifier: NCT01408030
Recruitment Status : Completed
First Posted : August 2, 2011
Results First Posted : October 19, 2018
Last Update Posted : October 19, 2018
Sponsor:
Collaborator:
HHT Foundation International
Information provided by (Responsible Party):
James Gossage, Augusta University

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.

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

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 123 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: North American Study of Epistaxis in HHT (NOSE)
Study Start Date : August 2011
Actual Primary Completion Date : September 2014
Actual Study Completion Date : September 2014


Arm Intervention/treatment
Placebo Comparator: Placebo spray
sterile saline
Drug: Sterile saline
0.9%, 0.1 ml spray in each nostril bid
Other Name: Saline

Active Comparator: Bevacizumab spray
bevacizumab 1%
Drug: Bevacizumab
1% solution in saline, 0.1 ml spray in each nostril bid
Other Names:
  • Avastin
  • Vascular endothelial growth factor (VEGF) inhibitor

Active Comparator: Estriol spray
Estriol 0.1%
Drug: Estriol
0.1% suspension in methylcellulose, 0.1 ml spray in each nostril bid
Other Name: Estrogen

Active Comparator: Tranexamic acid spray
tranexamic acid 10%
Drug: Tranexamic Acid
10% solution in saline, 0.1 ml spray in each nostril bid
Other Name: Lysteda




Primary Outcome Measures :
  1. Frequency of Epistaxis [ Time Frame: Weeks 5-12 of active treatment phase ]
    Bleeding episodes per week


Secondary Outcome Measures :
  1. Duration of Epistaxis [ Time Frame: 5-12 weeks of active treatment ]
    Total minutes of bleeding per week

  2. Hoag Epistaxis Severity Score [ Time Frame: 12 weeks ]
    Hoag Epistaxis Severity Score (ESS) is based on 6 nosebleed variables such as frequency and duration which are entered by patients. The ESS has a minimum value of 0 and maximum value of 10, with 10 representing more severe epistaxis.

  3. Hemoglobin Level [ Time Frame: 12 weeks ]
    grams/100 ml, assessed at week 12

  4. Number of Participants Requiring Red Blood Cell (RBC) Transfusion [ Time Frame: 12 weeks ]
    Number of participants requiring RBC transfusion during weeks 1-12

  5. Number of Participants With Treatment Failure [ Time Frame: Baseline through 12 weeks ]
    Treatment failure is defined as the occurrence of one or more of the following during the study: need for nasal surgery or chemical cautery or other new treatment modality to control epistaxis; transfusion of more than 12 units of RBC; severe complications such as acute myocardial infarction, venous thromboembolism, brain hemorrhage; or death



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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, 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
Saint 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
HHT Foundation International
Investigators
Principal Investigator: James R Gossage, MD Augusta University

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: James Gossage, Director of Pulmonary Vascular Diseases and HHT, Augusta University
ClinicalTrials.gov Identifier: NCT01408030     History of Changes
Other Study ID Numbers: GHSU 1008041
First Posted: August 2, 2011    Key Record Dates
Results First Posted: October 19, 2018
Last Update Posted: October 19, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by James Gossage, Augusta University:
epistaxis
HHT
bevacizumab
tranexamic acid
nosebleed
estrogen

Additional relevant MeSH terms:
Telangiectasis
Epistaxis
Telangiectasia, Hereditary Hemorrhagic
Vascular Diseases
Cardiovascular Diseases
Nose Diseases
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Hemorrhage
Pathologic Processes
Hemostatic Disorders
Hemorrhagic Disorders
Hematologic Diseases
Vascular Malformations
Cardiovascular Abnormalities
Congenital Abnormalities
Bevacizumab
Endothelial Growth Factors
Tranexamic Acid
Estrogens
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics