North American Study of Epistaxis in HHT (NOSE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Georgia Regents University
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: April 17, 2013
Last verified: April 2013
  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


Estimated Enrollment: 140
Study Start Date: August 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: July 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

Contacts
Contact: james r gossage, MD 706-721-6789 jgossage@gru.edu
Contact: melissa james, RN 706-721-8391 mejames@gru.edu

Locations
United States, California
University of California Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Polly Kay, RN    310-794-0376    pkay@mednet.ucla.edu   
Contact: Barbara Quinn         
Principal Investigator: Justin McWilliams, MD         
United States, Georgia
Georgia Regents University Recruiting
Augusta, Georgia, United States, 30912
Contact: Melissa James, RN    706-721-8391    mjames@gru.edu   
Contact: Janie Sims, RN    706-721-0470    jansims@gru.edu   
Principal Investigator: James Gossage, MD         
United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21205
Contact: Gina M Robinson, RN    410-502-3628    grobin11@jhmi.edu   
Contact: Christian Merlo, MD    410-502-7044    cmerlo@jhmi.edu   
Principal Investigator: Christian Merlo, MD         
United States, Missouri
Washington University School of Medicine Recruiting
St Louis, Missouri, United States, 63110
Contact: Sharon Heurman, RN    314-747-8174    sheuerman@dom.wustl.edu   
Principal Investigator: Murali Chakinala, MD         
United States, Oregon
Oregon Health Sciences University Recruiting
Portland, Oregon, United States, 97239
Contact: Farrar Carrie    503-494-4233    farrarc@ohsu.edu   
Contact: Matthew French    503-494-7004    frenchm@ohsu.edu   
Principal Investigator: Nathan Sautter, MD         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Renee Neuharth, BS    801-587-4877    Renee.Neuharth@hsc.utah.edu   
Principal Investigator: Kevin Whitehead, MD         
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: April 17, 2013
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:
Telangiectasia, Hereditary Hemorrhagic
Telangiectasis
Epistaxis
Nose Diseases
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Hemorrhage
Pathologic Processes
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders
Hematologic Diseases
Vascular Malformations
Cardiovascular Abnormalities
Congenital Abnormalities
Estrogens
Tranexamic Acid
Bevacizumab
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 14, 2014