1. Intranasal bevacizumab failed to reduce mean monthly epistaxis duration in patients with hereditary hemorrhagic telangiectasia in the three consecutive months following treatment
2. Intranasal bevacizumab does not provide significant improvements in nosebleed frequency, quality of life, number of red blood cell transfusions, or hemoglobin and ferritin levels
Evidence Rating Level: 1 (Excellent)
Study Rundown: Hereditary hemorrhagic telangiectasia (HHT) is a genetically inherited vascular disorder that is characterized by recurrent nosebleeds. These can often result in chronic anemia requiring iron supplementation or blood transfusions. While there are currently no definite medical or surgical treatments for the disorder, limited published reports have shown the benefit of IV bevacizumab, an anti-VEGF antibody, in patients with hepatic forms of HHT. Other cases have reported a potential role of intranasal bevacizumab with a phase I trial concluding its safety irrespective of the dose.
The current study is a phase 2, double-blinded, multicenter, randomized and placebo-controlled clinical trial that evaluated the efficacy of intranasal bevacizumab in controlling epistaxis in HHT patients. Eighty patients were randomized to either a placebo or one of three doses of bevacizumab over a 4-week treatment period. No significant improvements in mean epistaxis time were found across the groups. Further, no statistical differences were observed in the frequency of nosebleeds, quality of life, number of red blood cell transfusions, and hemoglobin and serum ferritin levels. Overall, the study showed no improvements in epistaxis in patients with HHT that were treated with intranasal bevacizumab. Originally, designed as a phase 2/3 clinical trial, the trial was stopped prior to phase 3 for treatment futility based on an interim analysis by an independent review committee.
Click to read the study in JAMA
Relevant Reading: Bevacizumab in Patients With Hereditary Hemorrhagic Telangiectasia and Severe Hepatic Vascular Malformations and High Cardiac Output
In-Depth [randomized clinical trial]: Patients were enrolled into this study if they were age 18 or older with clinically confirmed HHT and a history of epistaxis (mean total duration of more than 20 minutes per month for at least 3 months) with no nasal surgery during the trial period. These patients self-reported their baseline condition by completing nosebleed reporting grids. During the first stage of the study (phase 2 clinical trial), a placebo and three interim doses of nasal bevacizumab (25, 50, and 75 mg) were chosen. In the second stage of study (phase 3 clinical trial), the most optimal dose would be chosen and compared to placebo. Data were collected at each treatment visit and during a 6-month follow up period. Treatment consisted of 3 single-day intranasal treatments of bevacizumab or placebo across 14-day intervals. The primary outcome was the mean duration of epistaxis per month starting at the end of the treatment period. Secondary outcomes included mean monthly frequency pf nosebleeds, quality of life, number of red blood cell transfusions, and hemoglobin and serum ferritin levels. Mean monthly epistaxis duration levels were: 259.2 minutes in the 25 mg group, 244.0 minutes in the 50-mg group, 215.0 minutes in the 75 mg group, and 200.4 minutes in the placebo group. No adverse events were reported. Overall, no significant effects of intranasal bevacizumab on reducing primary or secondary outcome measures were found.
Image: PD
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