Telangiectasia, Hereditary HemorrhagicPhase 2NOSENCT01408030

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

A Phase 2 study testing Sterile saline, Bevacizumab and Estriol in people with Telangiectasia, Hereditary Hemorrhagic and Epistaxis, run by James Gossage at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Telangiectasia, Hereditary Hemorrhagic, Epistaxis
What is being tested?: Sterile saline, Bevacizumab and Estriol
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 123 participants
Where: 6 sitesUnited States
Study dates: Aug 2011to Sep 2014
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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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.

Who cannot join

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.
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.

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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.

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

Georgia Regents University
Augusta, Georgia, 30912
Johns Hopkins University
Baltimore, Maryland, 21205
University of California Los Angeles
Los Angeles, California, 90095
Oregon Health Sciences University
Portland, Oregon, 97239
University of Utah
Salt Lake City, Utah, 84132
Washington University School of Medicine
St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: North American Study of Epistaxis in HHT (NOSE)

Read the 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.

Conditions: Telangiectasia, Hereditary Hemorrhagic, Epistaxis
Being tested: Sterile saline, Bevacizumab, Estriol, Tranexamic Acid
Keywords: epistaxis, HHT, bevacizumab, tranexamic acid, nosebleed, estrogen
Medical subject headings: Telangiectasia, Hereditary Hemorrhagic, Epistaxis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Sterile salineDrug
Also called Saline
0.9%, 0.1 ml spray in each nostril bid
BevacizumabDrug
Also called Avastin, Vascular endothelial growth factor (VEGF) inhibitor
1% solution in saline, 0.1 ml spray in each nostril bid
EstriolDrug
Also called Estrogen
0.1% suspension in methylcellulose, 0.1 ml spray in each nostril bid
Tranexamic AcidDrug
Also called Lysteda
10% solution in saline, 0.1 ml spray in each nostril bid

Study groups in NCT01408030
Study group	Role	What they receive
Placebo spray	Placebo comparator	sterile saline Receives: Drug: Sterile saline
Bevacizumab spray	Active comparator	bevacizumab 1% Receives: Drug: Bevacizumab
Estriol spray	Active comparator	Estriol 0.1% Receives: Drug: Estriol
Tranexamic acid spray	Active comparator	tranexamic acid 10% Receives: Drug: Tranexamic Acid

What is being measured

The primary outcome is the main question the study is designed to answer.

Frequency of Epistaxis
Bleeding episodes per week
Measured: Weeks 5-12 of active treatment phase

Secondary outcomes (5)

Duration of Epistaxis
Total minutes of bleeding per week
Measured: 5-12 weeks of active treatment
Hoag Epistaxis Severity Score
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.
Measured: 12 weeks
Hemoglobin Level
grams/100 ml, assessed at week 12
Measured: 12 weeks
Number of Participants Requiring Red Blood Cell (RBC) Transfusion
Number of participants requiring RBC transfusion during weeks 1-12
Measured: 12 weeks
Number of Participants With Treatment Failure
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
Measured: Baseline through 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2011Sep 2014

First posted2 Aug 2011 (estimated)
Study startAug 2011
Primary completionSep 2014
Study completionSep 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Telangiectasia, Hereditary HemorrhagicStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 123 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01408030
Sponsor's protocol ID: GHSU 1008041
Acronym: NOSE
Status last verified: Oct 2018
First submitted: 1 Aug 2011
Last updated: 19 Oct 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

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.
PubMed 27599329

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 1
Topical TOR-582 Treatment of Epistaxis in HHT
Hereditary Hemorrhagic Telangiectasia (HHT), Epistaxis
RecruitingPhase 1/2
Harmony-HHT: ATV-1601 in Participants With Hereditary Hemorrhagic Telangiectasia (HHT)
Hereditary Hemorrhagic Telangiectasia (HHT), Osler Weber Rendu Disease
RecruitingObservational study
Quality of Life in Pediatric Participants With HHT
Hereditary Haemorrhagic Telangiectasia (HHT)
Not yet recruitingObservational study
Prevalence of Obstructive Sleep Apnea in HHT and HHT-specific Challenges in OSA-therapy - a Retrospective Cohort Study
Hereditary Hemorrhagic Telangiectasia (HHT), Obstructive Sleep Apnea (OSA)
Active, not recruitingPhase 1/2
A Study to Evaluate ALN-6400 in Healthy Volunteers and Patients With Hereditary Hemorrhagic Telangiectasia (HHT)
Hereditary Hemorrhagic Telangiectasia

All Telangiectasia, Hereditary Hemorrhagic trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: North American Study of Epistaxis in HHT (NOSE)
ClinicalTrials.gov ID: NCT01408030
Acronym / sponsor ID: NOSE / GHSU 1008041
Conditions: Telangiectasia, Hereditary Hemorrhagic, Epistaxis
Keywords: epistaxis, HHT, bevacizumab, tranexamic acid, nosebleed, estrogen
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 123 participants (actual)
Lead sponsor: James GossageUniversity, hospital or other
Collaborators: HHT Foundation International
Study start: Aug 2011
Primary completion: Sep 2014 (actual)
Study completion: Sep 2014 (actual)
First posted: 2 Aug 2011 (estimated)
Results: Posted 19 Oct 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Placebo spray	Placebo comparator	Drug: Sterile salinesterile saline
Bevacizumab spray	Active comparator	Drug: Bevacizumabbevacizumab 1%
Estriol spray	Active comparator	Drug: EstriolEstriol 0.1%
Tranexamic acid spray	Active comparator	Drug: Tranexamic Acidtranexamic acid 10%

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

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:
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.

Key exclusion criteria (9 listed)

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.
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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Sterile salineAlso: Saline0.9%, 0.1 ml spray in each nostril bid	Drug	Placebo spray
BevacizumabAlso: Avastin, Vascular endothelial growth factor (VEGF) inhibitor1% solution in saline, 0.1 ml spray in each nostril bid	Drug	Bevacizumab spray
EstriolAlso: Estrogen0.1% suspension in methylcellulose, 0.1 ml spray in each nostril bid	Drug	Estriol spray
Tranexamic AcidAlso: Lysteda10% solution in saline, 0.1 ml spray in each nostril bid	Drug	Tranexamic acid spray

Primary outcome

Frequency of Epistaxis
Time frame: Weeks 5-12 of active treatment phase
Bleeding episodes per week

5 secondary outcomes

Duration of Epistaxis
Time frame: 5-12 weeks of active treatment
Hoag Epistaxis Severity Score
Time frame: 12 weeks
Hemoglobin Level
Time frame: 12 weeks
Number of Participants Requiring Red Blood Cell (RBC) Transfusion
Time frame: 12 weeks
Number of Participants With Treatment Failure
Time frame: Baseline through 12 weeks

Results and safety

Results posted to the registry on 19 Oct 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Bevacizumab Spray	29	26
Estriol Spray	31	24
Tranexamic Acid Spray	33	32
Placebo Spray	28	25

Primary outcome: Frequency of Epistaxis

Time frame: Weeks 5-12 of active treatment phase. Median (Inter-Quartile Range). Unit: Bleeding episodes per week

Measure	Bevacizumab Spray n = 24	Estriol Spray n = 25	Tranexamic Acid Spray n = 30	Placebo Spray n = 27
Value	7.0 (4.5 to 10.5)	8.0 (4.0 to 12.0)	7.5 (3.0 to 11.0)	8.0 (3.0 to 14.0)

Bevacizumab Spray vs Estriol Spray vs Tranexamic Acid Spray vs Placebo Spray: p = 0.97, ANOVA

Population analysed: Participants were included in this analysis (106) if they had at least 3 weeks of data during weeks 5-12; therefore the number of participants analyzed do not equal the number who finished the active treatment phase (120). 2 patients were lost to follow up, 5 dropped out before week 5, 6 filled out diaries incorrectly, and 1 had no diary.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Weeks 1-24. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Bevacizumab Spray	0 of 29 (0%)	24 of 29 (82.8%)	0 of 29
Estriol Spray	0 of 30 (0%)	25 of 30 (83.3%)	0 of 30
Tranexamic Acid Spray	0 of 33 (0%)	26 of 33 (78.8%)	0 of 33
Placebo Spray	0 of 28 (0%)	23 of 28 (82.1%)	0 of 28

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 27599329Whitehead 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.
HHT Foundation websiteLink provided by the sponsor.
Individual participant dataSharing planned: No

Related trials for Telangiectasia, Hereditary Hemorrhagic

Not yet recruitingPhase 1
Topical TOR-582 Treatment of Epistaxis in HHT
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RecruitingPhase 1/2
Harmony-HHT: ATV-1601 in Participants With Hereditary Hemorrhagic Telangiectasia (HHT)
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Quality of Life in Pediatric Participants With HHT
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Prevalence of Obstructive Sleep Apnea in HHT and HHT-specific Challenges in OSA-therapy - a Retrospective Cohort Study
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

James R Gossage, MD principal investigator

Augusta University

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sterile saline, Bevacizumab and Estriol in people with Telangiectasia, Hereditary Hemorrhagic and Epistaxis, run by James Gossage at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency of Epistaxis (time frame: Weeks 5-12 of active treatment phase). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01408030, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2018.