North American Study of Epistaxis (NOSE Study)
Sponsored and Conducted by Cure HHT
PUBLICATION: Journal of American Medical Association; JAMA. 2016;316(9):943-951. doi:10.1001/jama.2016.11724
Important Update on the NOSE Study Funded by Cure HHT
The North American Study of Epistaxis in HHT completed enrollment with the last patient having been evaluated in July 2014. Between August 2011 and March 2014, Cure HHT enrolled 121 patients at six of the US HHT Centers of Excellence.
Interest in the treatment was actually so high that enrollment was slowed because patients were concerned about being placed on placebo. If it hadn't been apparent before, this observation further confirmed how important research is to finding treatments and a cure for our community.
While the preliminary results of the study were presented at the HHT scientific conference in June 2015, the study must be officially published before results can be shared with the public. The focus is now on featuring the study in a major medical journal so HHT experts around the world can critically review and draw their own conclusions.
The article was submitted to a renowned medical journal this week, and if accepted will hopefully be published in the next four months. Though we cannot release specific results at this time, we can say the study was well conducted and there were no significant side effects from the drugs. The majority of patients also noted some degree of symptom improvement!
At it's core, this study has taught us which drugs work and which don’t. Hopefully, we can build on this with even greater and quicker research participation in future studies. The more that patients get involved, the sooner we get results that impact the treatment of HHT.
Overview: The HHT Foundation has been listening to its members and over the last two years, the largest clinical study to date involving several North American HHT Centers of Excellence has been carefully designed. The North American Therapeutics Group (NATG), led by Dr. James Gossage, conducted a systematic review of published research published on different nosebleed therapies. The group had a list of agents that was honed down to a study of three and a placebo. The U.S. Federal Drug Administration (FDA) reviewed the application and asked for testing to ensure the agents were safe and stable in the spray bottles. The agents were tested and we received approval from the FDA.
This will be the largest multi-centered study of nosebleed treatment ever conducted and will be funded by members who have donated through the years to a special Epistaxis Fund.
Summary: The purpose of the NOSE Study is to carefully examine the benefit and safety of 3 nasal sprays for patients with HHT related epistaxis and definitively determine which of these are overall beneficial. Each of these sprays will approach the problem from a different mechanism of action. 140 patients with moderate to severe nosebleeds secondary to HHT, will be randomized to receive one of four intranasal sprays for a period of 12 weeks and then followed for an additional 12 weeks off therapy. A placebo arm has been included to allow an accurate estimate of both benefit and safety. The primary measure of effectiveness will be the frequency of epistaxis. Other measures of effectiveness will include the Hoag Epistaxis Severity Score (ESS), a quality of life survey, satisfaction with treatment, hemoglobin level, and transfusion requirements.
The spray agents are:
- Saline spray (Placebo);
- Estriol (a low dose estrogen);
- Tranexamic acid (a drug that promotes clotting), and
- Bevacizumab (also known as Avastin, a drug that might actually reverse abnormal blood vessel growth). The dose that will be used in the NOSE Study is 4mg per day, about 1% as potent as the intravenous dose. We expect that side effects will be minimal.
The HHT Foundation International is very grateful to the members who have contributed and continue to support this research. While it may appear that this clinical trial has taken a long time to develop, it is important to recognize that it needs to be done with scientific rigor so that the results provide the important treatment information that is so needed in HHT. One key element of our mission is to ad- vance therapeutic treatments for HHT patients. We take this commitment seriously and look forward to updating you on the progress!
The NATG Groups consists of the following members: James Gossage MD, Georgia Health Sciences University; Marie Faughnan MD, University of Toronto; Reed Pyeritz MD PhD, University of Pennsylvania; Paul Oh PhD, University of Florida; Michelle Letarte PhD, Toronto Hospital for Sick Children; Dennis Sprecher, MD, Cure HHT Board Member; Scott Olitsky, MD, Cure HHT Board Member; Marianne Clancy, Cure HHT Executive Director