EpistaxisPhase 4NOSTRILNCT04167085
NOrth American Study for the Treatment of Recurrent epIstaxis With DoxycycLine: The NOSTRIL Trial
A Phase 4 study testing Doxycycline in people with Epistaxis, run by University of California, Los Angeles at 1 site in United States.
Trial summary
The purpose of this research study is to determine whether Doxycycline can be used to control nosebleeds (epistaxis) for patients with Hereditary Hemorrhagic Telangiectasia (HHT). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Epistaxis
- What is being tested?
- Doxycycline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Dec 2017to 1 Jun 2021
- Phase
- Phase 4
- 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
- Diagnosis of definite HHT by the Curacao criteria or genetic diagnosis of HHT
- Epistaxis severity during observation month at least moderate by Epistaxis Severity Score (ESS) evaluation
- For female participants, a negative pregnancy test at Day -1 and agree to use birth control during treatment and for 28 days following cessation of Doxycycline
Who cannot join
- Use of medication(s) contraindicated with doxycycline use within 14 days prior to the study (including barbiturates, tegretol, dilantin, warfarin, isotretinoin)
Trial locations and contacts
1 site in 1 country.
United States1 site
100 UCLA Medical Plaza
Los Angeles, California, 90095
About this study
The purpose of this research study is to determine whether Doxycycline can be used to control nosebleeds (epistaxis) for patients with Hereditary Hemorrhagic Telangiectasia (HHT). Patients with HHT will be randomized to one of 2 study arms: Doxycycline or Placebo for a period of 2 months followed by a 1-month washout period before switching treatments for a further 2 months period. Observation and evaluation will continue for a period of one month after treatment is completed.
Read the detailed description
This study will analyze the effect of doxycycline on nosebleeds in hereditary hemorrhagic telangiectasia (HHT), a rare and debilitating medical condition. Patients with HHT have a variety of vascular abnormalities, including changes in their nasal vasculature that result in chronic, severe nosebleeds. These nosebleeds have been shown to significantly reduce the quality of life in HHT and can be severe enough to require emergent blood transfusion. Current therapies to control nosebleeds in HHT, which include both medications and surgical treatments, are inconsistently effective and associated with a variety of problematic side effects and complications.
Doxycycline is a common, FDA-approved antibiotic medication that has been used by physicians for decades. It is a safe medication that can be used on an outpatient basis for extended periods of time with minimal side effects. Recent research has shown that doxycycline is a potent inhibitor of angiogenesis, the process of new blood vessel development. Since the vascular abnormalities in HHT form due to uncontrolled angiogenesis, it follows that doxycycline may have potential in treating HHT. A growing body of research demonstrates the efficacy of doxycycline in treating a variety of vascular conditions, including cancer of the breast, duodenum, liver prostate, and lung. Our trial will be the first to analyze the efficacy of doxycycline in treating HHT epistaxis.
This a randomized, double-blind, crossover study design. Each patient will take both placebo and doxycycline. Since this is a cross-over study, half the participants will start out with taking placebo and half start with doxycyline and then switch halfway through. After a baseline observation period, participants will be given doxycycline at 100 mg twice a day, or an identical-appearing placebo, for a period of three months. Each month they will be seen be a physician, who will take a detailed clinical history and perform a physical examination. Further, each month the patient will have blood testing to assess blood loss, and fill out scientifically validated surveys to assess quality of life and the severity of bleeding. Following this three month treatment period, participants will be observed for one additional month, with one additional blood test and clinical assessment performed after this month.
- Conditions
- Epistaxis
- Being tested
- Doxycycline, Placebo
- Keywords
- Epistaxis, Hereditary Hemorrhagic Telangiectasia, HHT, Doxycycline, Nosebleed
- Medical subject headings
- Epistaxis, Telangiectasia, Hereditary Hemorrhagic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxycyclineDrug
Doxycycline, 100 mg twice a day for 2 months
PlaceboOther
Matching placebo, twice a day for 2 months
| Study group | Role | What they receive |
|---|---|---|
| Doxycycline, then Placebo | Experimental | Doxycycline for a period of 2 months followed by a 1-month washout period, and then placebo for a further 2 months period followed by a 1-month washout period. Receives: Drug: Doxycycline; Other: Placebo |
| Placebo, then Doxycycline | Experimental | Placebo for a period of 2 months followed by a 1-month washout period, and then Doxycycline for a further 2 months period followed by a 1-month washout period. Receives: Drug: Doxycycline; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Epistaxis
Change in number of bleeding episodes per week by participant self-report via nosebleed diary
Measured: Baseline, post-washout - approximately 6 months
Duration of Epistaxis
Change in duration of bleeding per week by patient self-report via nosebleed diary
Measured: Baseline, post-washout - approximately 6 months
Change in Severity of Epistaxis
Epistaxis Severity Scale (ESS) for Hereditary Hemorrhagic Telangiectasia, is based on 6 nosebleed variables such as frequency and duration which are reported by patients.The ESS has a minimum value of 0 and maximum value of 10, with 10 representing more severe epistaxis.
Measured: Baseline, post-washout - approximately 6-months
Secondary outcomes (5)
Change in Quality of Life
The 12-item Short Form (SF-12) is a survey designed for use with patients with multiple chronic conditions. This 12-item scale can be used to assess the physical and mental health of respondents. 10 of the 12 questions are answered on a 5-point Likert scale and 2 are answered on a 3-point Likert scale. The questions are then scored and weighted into 2 subscales, physical health and mental health. Respondents can have a score that ranges from 0-100 with 100 being the best score and indicating high physical or mental health.
Measured: Baseline, post-washout - approximately 6 months
Change in Ferritin Level
Measured: Baseline, post-washout - approximately 6 months
Change in Hemoglobin Level
Measured: Baseline, post-washout (approximately 6 months)
Change in Monthly Units of Packed Red Blood Cells (PRBCs) Transfused
Measured: Baseline, post-washout (approximately 6 months)
Incidence of Treatment Failure
Treatment failure, defined as need for nasal surgery or other epistaxis treatments
Measured: Baseline, post-washout (approximately 6 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2019
- Study start18 Dec 2017
- Primary completion1 Jun 2021
- Study completion1 Jun 2021
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.
- Other trials for EpistaxisStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Justin McWilliams, MD, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04167085
- Sponsor's protocol ID
- 16-001827
- Acronym
- NOSTRIL
- Status last verified
- Jun 2022
- First submitted
- 14 Nov 2019
- Last updated
- 20 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NOrth American Study for the Treatment of Recurrent epIstaxis With DoxycycLine: The NOSTRIL Trial
- ClinicalTrials.gov ID
- NCT04167085
- Acronym / sponsor ID
- NOSTRIL / 16-001827
- Conditions
- Epistaxis
- Keywords
- Epistaxis, Hereditary Hemorrhagic Telangiectasia, HHT, Doxycycline, Nosebleed
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Study start
- 18 Dec 2017 (actual)
- Primary completion
- 1 Jun 2021 (actual)
- Study completion
- 1 Jun 2021 (actual)
- First posted
- 18 Nov 2019 (actual)
- Results
- Posted 20 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to determine whether Doxycycline can be used to control nosebleeds (epistaxis) for patients with Hereditary Hemorrhagic Telangiectasia (HHT). Patients with HHT will be randomized to one of 2 study arms: Doxycycline or Placebo for a period of 2 months followed by a 1-month washout period before switching treatments for a further 2 months period. Observation and evaluation will continue for a period of one month after treatment is completed.
Detailed description
This study will analyze the effect of doxycycline on nosebleeds in hereditary hemorrhagic telangiectasia (HHT), a rare and debilitating medical condition. Patients with HHT have a variety of vascular abnormalities, including changes in their nasal vasculature that result in chronic, severe nosebleeds. These nosebleeds have been shown to significantly reduce the quality of life in HHT and can be severe enough to require emergent blood transfusion. Current therapies to control nosebleeds in HHT, which include both medications and surgical treatments, are inconsistently effective and associated with a variety of problematic side effects and complications.
Doxycycline is a common, FDA-approved antibiotic medication that has been used by physicians for decades. It is a safe medication that can be used on an outpatient basis for extended periods of time with minimal side effects. Recent research has shown that doxycycline is a potent inhibitor of angiogenesis, the process of new blood vessel development. Since the vascular abnormalities in HHT form due to uncontrolled angiogenesis, it follows that doxycycline may have potential in treating HHT. A growing body of research demonstrates the efficacy of doxycycline in treating a variety of vascular conditions, including cancer of the breast, duodenum, liver prostate, and lung. Our trial will be the first to analyze the efficacy of doxycycline in treating HHT epistaxis.
This a randomized, double-blind, crossover study design. Each patient will take both placebo and doxycycline. Since this is a cross-over study, half the participants will start out with taking placebo and half start with doxycyline and then switch halfway through. After a baseline observation period, participants will be given doxycycline at 100 mg twice a day, or an identical-appearing placebo, for a period of three months. Each month they will be seen be a physician, who will take a detailed clinical history and perform a physical examination. Further, each month the patient will have blood testing to assess blood loss, and fill out scientifically validated surveys to assess quality of life and the severity of bleeding. Following this three month treatment period, participants will be observed for one additional month, with one additional blood test and clinical assessment performed after this month.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Doxycycline, then Placebo | Experimental | Drug: Doxycycline, Other: PlaceboDoxycycline for a period of 2 months followed by a 1-month washout period, and then placebo for a further 2 months period followed by a 1-month washout period. |
| Placebo, then Doxycycline | Experimental | Drug: Doxycycline, Other: PlaceboPlacebo for a period of 2 months followed by a 1-month washout period, and then Doxycycline for a further 2 months period followed by a 1-month washout period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of definite HHT by the Curacao criteria or genetic diagnosis of HHT
- Epistaxis severity during observation month at least moderate by Epistaxis Severity Score (ESS) evaluation
- For female participants, a negative pregnancy test at Day -1 and agree to use birth control during treatment and for 28 days following cessation of Doxycycline
Key exclusion criteria (1 listed)
- Use of medication(s) contraindicated with doxycycline use within 14 days prior to the study (including barbiturates, tegretol, dilantin, warfarin, isotretinoin)
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 |
|---|---|---|
| DoxycyclineDoxycycline, 100 mg twice a day for 2 months | Drug | Doxycycline, then Placebo, Placebo, then Doxycycline |
| PlaceboMatching placebo, twice a day for 2 months | Other | Doxycycline, then Placebo, Placebo, then Doxycycline |
Primary outcome
Frequency of Epistaxis
Time frame: Baseline, post-washout - approximately 6 months
Change in number of bleeding episodes per week by participant self-report via nosebleed diary
Duration of Epistaxis
Time frame: Baseline, post-washout - approximately 6 months
Change in duration of bleeding per week by patient self-report via nosebleed diary
Change in Severity of Epistaxis
Time frame: Baseline, post-washout - approximately 6-months
Epistaxis Severity Scale (ESS) for Hereditary Hemorrhagic Telangiectasia, is based on 6 nosebleed variables such as frequency and duration which are reported by patients.The ESS has a minimum value of 0 and maximum value of 10, with 10 representing more severe epistaxis.
5 secondary outcomes
Change in Quality of Life
Time frame: Baseline, post-washout - approximately 6 months
Change in Ferritin Level
Time frame: Baseline, post-washout - approximately 6 months
Change in Hemoglobin Level
Time frame: Baseline, post-washout (approximately 6 months)
Change in Monthly Units of Packed Red Blood Cells (PRBCs) Transfused
Time frame: Baseline, post-washout (approximately 6 months)
Incidence of Treatment Failure
Time frame: Baseline, post-washout (approximately 6 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Doxycycline in people with Epistaxis, run by University of California, Los Angeles at 1 site 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 3 inclusion and 1 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 20 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 20 Jul 2022). 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: Baseline, post-washout - approximately 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Jul 2022.