Randomized Trial for Pazopanib in HHT-Related Bleeding
Abstract
Hereditary hemorrhagic telangiectasia (HHT) is a rare disease that causes abnormal blood vessels. Typically, arteries carrying blood from the heart will connect to smaller vessels called capillaries, which carry the blood throughout tissues for nutrient and oxygen exchange. The capillaries then carry the blood back to the heart through veins. In HHT, patients form abnormal connections between the blood vessels, skipping the capillary networks. These connections are at risk for rupture and bleeding. These malformations are known as arteriovenous malformations (AVMs), with the small mucosal ones often called telangiectasias. Almost all HHT patients experience nosebleeds from telangiectasias inside the nose. These can be frequent, sudden, and severe. Chronic nose bleeding can lead to anemia, fatigue, loss of sleep, and poor quality of life. In addition, HHT patients often require iron infusion or blood transfusions to maintain their health due to excess blood loss. Currently, there are no FDA-approved medications to help alleviate bleeding for HHT patients. The Department of Defense Peer Reviewed Medical Research Program generously provides funding for clinical trials in various topic areas, one of which is vascular malformations. The vascular malformations in HHT patients are caused by a genetic defect related to the growth and maturation of these vessels, but greatly amplified by enhanced vessel construction driven from overproduction of a vascular endothelial growth factor (VEGF). This is similar to the mechanism by which arteries develop to nourish and support growth of some cancerous tumors. Though HHT is not a type of cancer, cancer drugs that target vascular growth factors may help HHT patients have fewer blood vessel malformations and less bleeding. A few research studies in HHT patients have looked at a cancer therapeutic called Pazopanib that inhibits VEGF. The results are very promising; HHT patients treated with a very low dose of Pazopanib experience less bleeding and their anemia improves. However, these studies have been small and not well controlled. To move forward to see if Pazopanib could become an FDA-approved treatment for HHT patients, a randomized, placebo-controlled clinical trial must be executed. Patients with HHT who experience anemia and demonstrate relatively severe chronic nose bleeding will be enrolled in the proposed study. Forty (40) patients will receive a small, daily dose of Pazopanib, while 20 patients will receive a placebo pill. No one will know if they are receiving the actual drug or the placebo treatment. During the 24 weeks of the study, patients will be monitored very closely through blood work, doctor’s visits, and other tests. For those whose treatment offered benefit, the patient will have the option to continue the drug for another 6 months, which allows us to monitor for both safety and maintenance of effect. Our placebo population will be offered the chance to go onto drug in a similar fashion to those who started the study treatment at the beginning of the trial. The goal of this study is to see if this drug improves anemia and reduces bleeding in HHT patients, while avoiding complications. As a cancer therapy, this drug is given in a high dose and has some adverse side effects, particularly affecting the liver and measures of blood pressure. During the previous studies, a small dose did not cause significant adverse effects, but a larger and longer clinical trial is necessary to be sure Pazopanib is safe at a low dose. The United States alone has between 30 and 60 thousand HHT patients. Many HHT patients are living with such severe nosebleeds that it affects their personal and social lives. There is hesitation to participate in daily activities for fear of heavy bleeding. Chronic bleeding disrupts quality of life in addition to being costly to their health. A daily pill that can be taken at home with little to no side effects that could reduce bleeding and impr
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110827
Entities
People
- James Gossage
Organizations
- Augusta University
- United States Army