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Telangiectasia, Hereditary HemorrhagicPhase 2EPICURENCT03954782

Efficacy of Nintedanib Per os as a Treatment for Epistaxis in HHT Disease.

A Phase 2 study testing Nintedanib 150 mg and 100 mg soft capsules in people with Telangiectasia, Hereditary Hemorrhagic and Rendu Osler Disease, run by Hospices Civils de Lyon at 8 sites in France.

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 recognized manifestations of HHT are all due to abnormalities in vascular structure. Epistaxis are spontaneous, very variable, may occur as often as several times every day, and are recurrent in 90% of patients and associated with chronic and severe anemia in 2-10%. They also significantly reduce quality of life. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nintedanib 150 mg and 100 mg soft capsules
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
61 participants
Where
8 sitesFrance
Study dates
22 Jun 2020to 24 Feb 2023
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Age > 18 years old
  • Patients who have given their free informed and signed consent
  • Patients affiliated to a social security scheme or similar
  • Patients monitored for clinically confirmed HHT and/or with molecular biology confirmation
  • Patient with an Epistaxis Severity Score (ESS) > 4

Who cannot join

  • Pregnant woman or woman of child bearing potential
  • Woman who are breast feeding.
  • Patient who is protected adults under the terms of the law (French Public Health Code).
  • Participation in another interventional clinical trial which may interfere with the proposed trial
  • Active infection.
  • (AST, ALT > 1,5 fold upper limit of normal (ULN) and/or Bilirubin > 1,5 fold upper limit of normal (ULN).
Show all 22Show fewer
  • Severe renal impairment
  • Presence of non-treated pulmonary arteriovenous malformations accessible to a treatment on CT scan within 5 years.
  • Patients with hemoptysis or hematuria within 12 weeks prior to inclusion.
  • Patients with active gastro-intestinal (GI) bleeding or GI ulcers within 12 months prior to inclusion.
  • Presence of cerebral arteriovenous malformation.
  • Patients who require full-dose therapeutic anticoagulation (e.g. vitamin K antagonist or heparin, dabigatran) or high dose antiplatelet therapy, , patients under anticoagulation with rivaroxaban, apixaban and epixaban.
  • Patients with P-glycoprotein (P-gp) substrates/inducers/inhibitors (e.g.: ketoconazole, erythromycin, cyclosporine, rifampicin, carbamazepine, phenytoin, and St. John's Wort).
  • Patients with known coronary artery disease or recent history of myocardial infarction (within 1 year).
  • Known inherited predisposition to thrombosis or thrombotic events( including stroke and transient ischemic attack, excluded superficial venous thrombosis) within 12 months prior to inclusion.
  • Patients with QTc prolongation
  • Hypersensitivity to nintedanib, peanut or soya, or to any of the excipients.
  • Patient who incompletely filled in epistaxis grids within 8 weeks prior to inclusion.
  • Patient who have received intravenous bevacizumab within 6 months prior to inclusion.
  • Patient who had surgery (including ENT (Ear, Nose and Throat Specialist) surgery) within 12 weeks prior to inclusion.
  • Unhealed wound.
  • Planned major surgery within the next 3 months, including liver transplantation, major abdominal or intestinal surgery.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

France8 sites

  • CHU d'Angers

    Angers

  • Hôpital Femme-Mère-Enfant-Centre de Référence pour la maladie de Rendu-Osler

    Bron

  • CHU Clermont Ferrand

    Clermont-Ferrand

  • CHU de Marseille-Hôpital la conception

    Marseille

  • CHU de Montpellier-Hôpital St Eloi

    Montpellier

  • Hôpital Tenon

    Paris

  • CHRU - Hôpital J.Bernard

    Poitiers

  • CHU de Rennes-Hôpital Pontchaillou

    Rennes

Other trials in France

About this study

Official title: Efficacy of Nintedanib Per os as a Treatment for Epistaxis in HHT Disease. A National, Randomized, Multicentre Phase II Study

The recognized manifestations of HHT are all due to abnormalities in vascular structure. Epistaxis are spontaneous, very variable, may occur as often as several times every day, and are recurrent in 90% of patients and associated with chronic and severe anemia in 2-10%. They also significantly reduce quality of life.

Blood transfusions are sometimes required in 10-30% of patients. Previous studies showed that antiangiogenic treatments such as anti-VEGF treatment (bevacizumab) administered intravenously was efficient on epistaxis and dramatically reduced nosebleeds.

Read more

Tyrosine kinase inhibitors are anti-angiogenic molecules which are available orally and could therefore overcome the difficulties encountered with bevacizumab. The investigator hypothesized that nintedanib, acting by indirect inhibition of the VEGF receptor should allow a reduction of epistaxis in HHT patient.

Nintedanib has been used in one HHT patient following the diagnosis of Insterstitial Pulmonary Fibrosis (published case report in 2017, Kovacs et al) with encouraging results.

The aim is to evaluate efficacy of nintedanib for the treatment of epistaxis in HHT patients

Being tested
Nintedanib 150 mg and 100 mg soft capsules, Oral treatment of placebo soft capsule
Keywords
Hereditary Hemorrhagic Telangiectasia (HHT), antiangiogenic therapy, Tyrosine Kinase Inhibitor, Nintedanib
Medical subject headings
Telangiectasia, Hereditary Hemorrhagic

What participants receive

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

  • Nintedanib 150 mg and 100 mg soft capsulesDrug

    Nintedanib 150 mg soft capsules twice daily approximately 12 hours apart (i.e. 300 mg/day) for 12 weeks. In case of adverse reaction a dose reduction at 200 mg/day (100 mg twice daily) can be prescribe.

  • Oral treatment of placebo soft capsuleDrug

    Placebo soft capsules (identical to 150 mg and 100 mg soft capsules)

Study groups in NCT03954782
Study groupRoleWhat they receive
NintedanibExperimentalOral treatment of Nintedanib 150 mg soft capsule
Receives: Drug: Nintedanib 150 mg and 100 mg soft capsules
PlaceboPlacebo comparatorOral treatment of placebo soft capsule
Receives: Drug: Oral treatment of placebo soft capsule

What is being measured

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

  1. Epistaxis duration assessed on epistaxis grids completed by the patients.

    Measured: 12 weeks

Secondary outcomes (19)

  1. number of adverse events

    Measured: 6 months

  2. number of adverse events

    Measured: 12 weeks

  3. number of adverse events

    Measured: 24 weeks

  4. Efficacy or nintedanib assessed by ESS (Epistaxis Severity Score) questionnaire

    This score assess the severity of epistaxis (minimum 0 corresponds to "none" and maximum 10 corresponds to"severe")

    Measured: 12 weeks

  5. Efficacy or nintedanib assessed by ESS questionnaire

    This score assess the severity of epistaxis (minimum 0 corresponds to "none" and maximum 10 corresponds to"severe")

    Measured: 24 weeks

  6. duration of epistaxis all over the study. Assessment on epistaxis grids completed by the patients.

    Measured: 12 weeks

  7. duration of epistaxis assessed on epistaxis grids completed by the patients.

    Measured: 24 weeks

  8. duration of epistaxis assessed on epistaxis grids completed by the patients.

    Measured: 12 weeks

  9. frequency of epistaxis assessed on epistaxis grids completed by the patients.

    Measured: 24 weeks

  10. Quality of life assessed by SF36 (Short Form 36) questionnaire

    Measured: 12 weeks

  11. Quality of life assessed by SF36 questionnaire

    Measured: 24 weeks

  12. number of red blood cell transfusions

    Measured: 12 weeks

  13. number of red blood cell transfusions

    Measured: 24 weeks

  14. number of iron infusions

    Measured: 12 weeks

  15. number of iron infusions

    Measured: 24 weeks

  16. hemoglobin level

    Measured: 12 weeks

  17. hemoglobin level

    Measured: 24 weeks

  18. ferritin level

    Measured: 12 weeks

  19. ferritin level

    Measured: 24 weeks

Timeline

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

  1. First posted17 May 2019
  2. Study start22 Jun 2020
  3. Primary completion24 Feb 2023
  4. Study completion24 Feb 2023

Resources

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
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03954782
Sponsor's protocol ID
69HCL19_0003
Other IDs
2019-002593-31, 2019
Acronym
EPICURE
Status last verified
Aug 2023
First submitted
15 May 2019
Last updated
1 Aug 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Hermann R, Grobost V, Le-Guillou X, Lavigne C, Parrot A, Riviere S, Seguier J, Fargeton AE, de-Montigny A, Huot M, Decullier E, Roux A, Gervaise C, Cartier C, Dufour X, Grall M, Jegoux F, Laccourreye L, Michel J, Saroul N, Wagner I, Kerjouan M, Dupuis-Girod S. Effect of oral nintedanib vs placebo on epistaxis in hereditary hemorrhagic telangiectasia: the EPICURE multicenter randomized double-blind trial. Angiogenesis. 2024 Dec 24;28(1):9. doi: 10.1007/s10456-024-09962-4.

    PubMed 39718659

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nintedanib 150 mg and 100 mg soft capsules in people with Telangiectasia, Hereditary Hemorrhagic and Rendu Osler Disease, run by Hospices Civils de Lyon at 8 sites in France.

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 5 inclusion and 22 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 1 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in France. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Epistaxis duration assessed on epistaxis grids completed by the patients. (time frame: 12 weeks). 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 NCT03954782, 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 1 Aug 2025.

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