Submucosal Bevacizumab for the Management of Recurrent Epistaxis in Patients With Hereditary Hemorrhagic Telangiectasia (HHT)

The treatment, regardless of participation in the proposed research, is to bring the
patients to the operating room where under general anesthesia the nose is suctioned clean of
blood clot, crust and secretion. The mucosa is then injected with a local anesthetic with
adrenaline to reduce discomfort and to reduce bleeding. The nasal mucosa is treated with a
KTP laser in our standard fashion. A 100mg of Avastin delivered in 4cc is then diluted with
4cc of normal saline to a total volume of 8cc. The dilution is made not for any known
difference in treatment but rather it normally takes a minimum of 8cc to properly inject the
nasal mucosa. The 1% Bevacizumab is then injected submucosally throughout the nasal cavity
sparing the mucosa of the cartilage and the septum. The nasal cavity is then sprayed with
2cc of a fibrin sealant (EVICEL) this reduces postoperative bleeding and facilitates healing
from the laser therapy. It has nothing to do with the Bevacizumab injection. The patient is
then awakened and returned to the recovery room and discharged home. Beginning in
approximately one week the patient is instructed to begin their hypertonic pulsatile nasal
irrigations. They will follow-up in the clinic at 1 month. The data collection form is
attached. Prior to treatment patient completes the HHT epistaxis severity score, blood is
drawn for hematocrit, hemoglobin and serum feritin levels. Women of childbearing age all
have a urine pregnancy test, required both by anesthesia and for the Bevacizumab study as
well. Patients are followed monthly for the first 6 months. At 3 and 6 months the blood
tests are repeated. For those living in San Diego they can be performed at UCSD. For those
living outside the San Diego area they can be repeated by their primary care physician. For
the ensuing 18 months patients are followed monthly either electronically or by telephone.
ESS scores are calculated. Laboratory tests are not repeated. Patients are followed-up until
such time as they begin re-bleeding and their ESS scores increase either above 2 or by 1
point above their 1 month post-op evaluation. Experience to date with 20 or 30 patients is
that bleeding ceases within 1 to 2 weeks. Hence the 1 month score should be their optimum
result. Adverse events will be recorded and appropriately reported to the IRB.

A new epistaxis severity score (ESS) has been developed and tested by the HHT Foundation. We
have used this for the past several months and found it to be an excellent measure of HHT
epistaxis. A copy is attached.

The minimum sample size is 10 patients. Study duration is planned for 24 months and if more
patients are recruited they will be included. If fewer patients are recruited the study may
be extended. Data will be reported by means and standard deviations. Patients will be
compared individually and collectively to their pretreatment data specifically hematocrit,
hemoglobin, serum ferritin and epistaxis severity score.

Inclusion Criteria:

- Adults over the age of 18, both male and non-pregnant females capable of making
informed consent who have HHT by Curacao criteria and whose nasal bleeding due to HHT
is of such a magnitude that it requires medical care.

- Females of childbearing age will be given a pregnancy test as a preliminary measure
to ensure that those who become involved are not at risk.

- Generally these patients will have an ESS score of 5 or greater. However on occasion
an individual with a score between 2 and 5 but not capable of cleansing their nose
adequately to be involved in a Bevacizumab spray treatment may be included.