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6214: Sirolimus for Nosebleeds in HHT: A Phase II Pilot Study


Hereditary hemorrhagic telangiectasia (HHT) is a hereditary vascular condition characterized by the development of abnormal connections between arteries and veins throughout the body, called vascular malformations (abnormally formed veins). The abnormally formed veins in HHT lead to chronic recurrent hemorrhage (heavy bleeding), for which there are currently no proven medical therapies to control the heavy bleeding in HHT patients. The most common symptom of the hereditary hemorrhagic telangiectasia (HHT) disease is epistaxis, which affects 90% of adults with HHT, negatively affects quality of life and often causes anemia.

Sirolimus has been identified as a potential pathway-based therapy for HHT. Pre-clinical research has suggested that the way HHT develops includes an overactive protein pathway. Sirolimus has been found to work to prevent the effects of the overactive protein that results in vascular malformations in a HHT. There is considerable experience using sirolimus in post-transplant patients and growing experience using routine sirolimus in patients with vascular anomalies. However, there is very limited data of use of this drug in HHT. This pilot study will look at the safety and effectiveness sirolimus, for epistaxis in patients with HHT.

The research aims are:

  1. To determine the safety of oral sirolimus in patients with HHT, with moderate or severe epistaxis
  2. To measure the effect of oral sirolimus on epistaxis, compared to baseline epistaxis
  3. To explore biomarkers variability over time, on/off therapy and association with epistaxis

About This Study

This is a Phase II clinical trial and will include 10 participants who are seen in the St. Michael’s HHT clinic. Participant involvement will last for approximately 9 months (36 weeks). The first 3 months is the baseline period, where participants will keep a daily diary to assess baseline epistaxis. This will be followed by 3 months of study drug intake. For the final 3 months, participants will be in a follow-up period, where they stop taking study drug.

Participants will need to visit the clinic at screening visit (study start) and 3, 4.5, 6, 9 months and any required unscheduled visit for safety assessment. Follow-up phone call will also occur during week one and every two weeks when there is no clinic visits for the duration of the study.

Throughout the study, participants will be asked to:

  • Keep a daily diary of nose bleeds (epistaxis)
  • Completed the Epistaxis Severity Score questionnaire at clinic visits
  • Complete medical history and physical examination at clinic visits
  • Provide a blood sample for research to monitor changes in laboratory values

Targeted Enrollment

To be eligible to participate, participants must fulfill the following eligibility criteria:

  • Definite clinical HHT diagnosis (at least 3 clinical Curacao criteria) or genetic diagnosis of HHT.
  • Over 18 years of age
  • Epistaxis at least 15 min per week
  • COVID-19 Vaccine (2 doses minimum)
  • Ability to give informed consent, including compliance with requirements of the study

Individuals are NOT eligible to participate if:

  • HHT is not diagnosed in that individual
  • The individual cannot provide consent
  • Have an allergy/intolerance to study drug or related agents
  • Have an unstable medical illness
  • Have an acute infection
  • Females are pregnant or breastfeeding or plan to become pregnant during the duration of study
  • Women of childbearing potential are not on effective contraception
  • Individuals are immunocompromised
  • Have a history of malignancies
  • Have known untreated dyslipidemia

How to Join This Study

Contact the St. Michael’s Hospital HHT clinic.