Effects of Pazopanib on Hereditary Hemorrhagic Telangiectasia Related Epistaxis and Anemia (Paz)


About this study

The objective of Part A of this study is to assess the pharmacokinetics (PK) of pazopanib in Hereditary Hemorrhagic Telangiectasia (HHT) participants.  The objective of Parts B and C of this study is to assess the effects of up to 24 weeks of pazopanib treatment on duration of epistaxis or level of serum hemoglobin in the Severe Cohort.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • A definite diagnosis of hereditary hemorrhagic telangiectasia is defined as having at  least 3 of the following criteria:  
    • Spontaneous and recurrent epistaxis;
    • Multiple telangiectasias at characteristic sites: lips, oral cavity, fingers, nose;
    • Visceral lesions: GI telangiectasia, pulmonary, hepatic, cerebral or spinal AVMs.  
  • A first degree relative with hereditary hemorrhagic telangiectasia according to these criteria OR a definite diagnosis of hereditary hemorrhagic telangiectasia is defined as having a gene sequencing diagnosis of hereditary hemorrhagic telangiectasia:
    • Epistaxis due to hereditary hemorrhagic telangiectasia at least 2 x per week, for a  cumulative duration of at least 25 minutes per week;
    • Epistaxis is clinically stable during the 12 weeks prior to screening in the clinical  judgment of the investigator (i.e., no major changes in frequency or duration of  epistaxis);
    • Participant agrees not to undergo cautery of nasal telangiectasias or take any experimental therapies for hereditary hemorrhagic telangiectasia other than the study drug while participating in the study.
  • Male or female [non-child bearing potential].

Exclusion Criteria:  

  • Participant has known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib that in the opinion of the investigator contradicts their participation.
  • Currently has untreated cerebral arterio-venous malformations (AVMs), cerebral  arteriovenous fistulae, or cerebral cavernous malformations (CCMs) (Note: MRI scan does not need to be repeated at screening if AVMs, arterio-venous fistulas and CCMs were absent on a scan at age ≥ 18 years).  
  • Currently has perfused pulmonary AVMs with feeding artery diameter > 3mm.  
  • Known significant bleeding sources other than nasal or gastrointestinal.
  • Systemic use of a vascular endothelial growth factor inhibitor in the past 3 months or  previous enrollment in this study.
  • Active and recent onset of clinically significant diarrhea.
  • Current or recent (in the last 5 years) malignancies (except non-melanoma skin cancers).
  • Participant has had major surgery (e.g., surgical ligation of an AVM) or trauma within 28 days or had minor surgical procedures (e.g., central venous access line removal)  within 7 days prior to dosing, the latter representing a recent wound, fracture or ulcer.
  • Participant has a planned surgery during the period to include active treatment and 6 weeks of follow up.  
  • Participant has clinically significant gastrointestinal abnormalities (other than  hereditary hemorrhagic telangiectasia related vascular lesions).
  • Participant during the 6 months prior to first dose of study drug has a history of cerebrovascular accident (including transient ischemic attacks), pulmonary embolism, untreated deep vein thrombosis (DVT), myocardial infarction, or any other thrombotic event.
  • QT corrected interval ≥ 450 msec, based on averaged QT corrected interval values of triplicate ECGs obtained over a brief recording period.
  • Hemoglobin < 6 g/dL.
  • Platelets < 100 x 10^9/L.  
  • International normalized ratio (INR) >1.2 x upper limit of normal and activated partial  thromboplastin time (aPTT) > 1.2 x upper limit of normal.  
  • Alanine Transaminase > 2 x upper limit of normal.
  • Bilirubin > 1.5 x upper limit of normal (isolated bilirubin > 1.5 x upper limit of normal  is acceptable if bilirubin is fractionated and direct bilirubin < 35%).  
  • Participant has poorly controlled hypertension [defined as systolic blood pressure  (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg.  
  • Substantive renal disease (eGFR < 30 mL/min/1.73m^2 calculated using the Cockcroft-Gault  formula).
  • Echo derived left ventricular ejection fraction < 30%.
  • Thyroid stimulating hormone > upper limit of normal.  
  • Urine protein to creatinine ratio > 0.3.
  • Neutrophil count < 1500/mm^3.

Eligibility last updated 10/5/21. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Vivek Iyer, M.D., M.P.H.

Contact us for the latest status

Contact information:

Pulmonary Clinical Research Unit

(800) 753-1606


More information


  • Hereditary hemorrhagic telangiectasia (HHT) is a rare angiogenic disorder causing chronic gastrointestinal bleeding, epistaxis, and severe anemia. Pazopanib is an oral multi-kinase angiogenesis inhibitor with promise to treat bleeding in HHT. We analyzed outcomes of HHT patients with the most severe bleeding causing RBC transfusion dependence treated on a predefined institutional pazopanib treatment pathway (with data collected retrospectively). The primary endpoint was achievement of transfusion independence. Secondary endpoints included hemoglobin, epistaxis severity score, RBC transfusion and iron infusion requirements, number of local hemostatic procedures, ferritin and transferrin saturation, compared using paired and repeated measures mean tests. Thirteen transfusion-dependent HHT patients received pazopanib [median (range) dose 150 (25-300) mg daily)] for a median of 22 months. All patients achieved transfusion independence. Compared with pretreatment, pazopanib increased mean hemoglobin by 4.8 (95% CI, 3.6-5.9) g/dL (7.8 vs. 12.7 g/dL, P < 0.0001) and decreased mean epistaxis severity score by 4.77 (3.11-6.44) points (7.20 vs. 2.43 points, P < 0.0001) after 12 months of treatment. Compared with 3 months of pretreatment, RBC transfusions decreased by 93% (median of 16.0 vs. 0.0 units, P < 0.0001) and elemental iron infusion decreased by 92% (median of 4500 vs. 0 mg, P = 0.005) during the first 3 months of treatment; improvements were maintained over time. Pazopanib was well-tolerated: hypertension, lymphocytopenia, and fatigue were the most common TEAEs. In conclusion, pazopanib was safe and effective to manage severe bleeding in HHT, liberating all patients from transfusion dependence and normalizing hematologic parameters at doses lower than used to treat malignancies. These findings require confirmation in a randomized trial. Read More on PubMed
  • A prospective, qualitative study was conducted to develop a patient-reported outcome measure (PROM) for daily administration via electronic diary (eDiary) to assess the severity of nosebleeds in patients with hereditary hemorrhagic telangiectasia (HHT), in accordance with Food and Drug Administration (FDA) PROM guidance criteria. Read More on PubMed

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