PMID- 27599329 OWN - NLM STAT- MEDLINE DCOM- 20161031 LR - 20170913 IS - 1538-3598 (Electronic) IS - 0098-7484 (Linking) VI - 316 IP - 9 DP - 2016 Sep 6 TI - Effect of Topical Intranasal Therapy on Epistaxis Frequency in Patients With Hereditary Hemorrhagic Telangiectasia: A Randomized Clinical Trial. PG - 943-51 LID - 10.1001/jama.2016.11724 [doi] AB - IMPORTANCE: Epistaxis is a major factor negatively affecting quality of life in patients with hereditary hemorrhagic telangiectasia (HHT; also known as Osler-Weber-Rendu disease). Optimal treatment for HHT-related epistaxis is uncertain. OBJECTIVE: To determine whether topical therapy with any of 3 drugs with differing mechanisms of action is effective in reducing HHT-related epistaxis. DESIGN, SETTING, AND PARTICIPANTS: The North American Study of Epistaxis in HHT was a double-blind, placebo-controlled randomized clinical trial performed at 6 HHT centers of excellence. From August 2011 through March 2014, there were 121 adult patients who met the clinical criteria for HHT and had experienced HHT-related epistaxis with an Epistaxis Severity Score of at least 3.0. Follow-up was completed in September 2014. INTERVENTIONS: Patients received twice-daily nose sprays for 12 weeks with either bevacizumab 1% (4 mg/d), estriol 0.1% (0.4 mg/d), tranexamic acid 10% (40 mg/d), or placebo (0.9% saline). MAIN OUTCOMES AND MEASURES: The primary outcome was median weekly epistaxis frequency during weeks 5 through 12. Secondary outcomes included median duration of epistaxis during weeks 5 through 12, Epistaxis Severity Score, level of hemoglobin, level of ferritin, need for transfusion, emergency department visits, and treatment failure. RESULTS: Among the 121 patients who were randomized (mean age, 52.8 years [SD, 12.9 years]; 44% women with a median of 7.0 weekly episodes of epistaxis [interquartile range IQR, 3.0-14.0]), 106 patients completed the study duration for the primary outcome measure (43 were women [41%]). Drug therapy did not significantly reduce epistaxis frequency (P = .97). After 12 weeks of treatment, the median weekly number of bleeding episodes was 7.0 (IQR, 4.5-10.5) for patients in the bevacizumab group, 8.0 (IQR, 4.0-12.0) for the estriol group, 7.5 (IQR, 3.0-11.0) for the tranexamic acid group, and 8.0 (IQR, 3.0-14.0) for the placebo group. No drug treatment was significantly different from placebo for epistaxis duration. All groups had a significant improvement in Epistaxis Severity Score at weeks 12 and 24. There were no significant differences between groups for hemoglobin level, ferritin level, treatment failure, need for transfusion, or emergency department visits. CONCLUSIONS AND RELEVANCE: Among patients with HHT, there were no significant between-group differences in the use of topical intranasal treatment with bevacizumab vs estriol vs tranexamic acid vs placebo and epistaxis frequency. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01408030. FAU - Whitehead, Kevin J AU - Whitehead KJ AD - Division of Cardiovascular Medicine and Pediatric Cardiology, Utah HHT Center of Excellence, University of Utah, Salt Lake City2George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, Utah. FAU - Sautter, Nathan B AU - Sautter NB AD - Oregon Sinus Center, Department of Otolaryngology-Head and Neck Surgery, Oregon Health & Science University, Portland. FAU - McWilliams, Justin P AU - McWilliams JP AD - Division of Interventional Radiology, Department of Radiology, UCLA HHT Center of Excellence, David Geffen School of Medicine at UCLA, Los Angeles, California. FAU - Chakinala, Murali M AU - Chakinala MM AD - Division of Pulmonary and Critical Care, Washington University School of Medicine, St Louis, Missouri. FAU - Merlo, Christian A AU - Merlo CA AD - Division of Pulmonary and Critical Care, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Johnson, Maribeth H AU - Johnson MH AD - Department of Biostatistics and Epidemiology, Augusta University, Augusta, Georgia. FAU - James, Melissa AU - James M AD - Division of Pulmonary and Critical Care Medicine, Augusta University, Augusta, Georgia. FAU - Everett, Eric M AU - Everett EM AD - O'Brien Pharmacy, Mission, Kansas. FAU - Clancy, Marianne S AU - Clancy MS AD - Cure HHT, Monkton, Maryland. FAU - Faughnan, Marie E AU - Faughnan ME AD - Toronto HHT Program, Division of Respirology, Department of Medicine, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada12Keenan Research Centre and Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada. FAU - Oh, S Paul AU - Oh SP AD - Department of Physiology and Functional Genomics, University of Florida, Gainesville. FAU - Olitsky, Scott E AU - Olitsky SE AD - Department of Ophthalmology, Children's Mercy Hospital, Kansas City, Missouri. FAU - Pyeritz, Reed E AU - Pyeritz RE AD - Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia. FAU - Gossage, James R AU - Gossage JR AD - Division of Pulmonary and Critical Care Medicine, Augusta University, Augusta, Georgia. LA - eng SI - ClinicalTrials.gov/NCT01408030 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Antifibrinolytic Agents) RN - 2S9ZZM9Q9V (Bevacizumab) RN - 6T84R30KC1 (Tranexamic Acid) SB - IM MH - Administration, Intranasal MH - Administration, Topical MH - Adult MH - Aged MH - Angiogenesis Inhibitors/*administration & dosage MH - Antifibrinolytic Agents/administration & dosage MH - Bevacizumab/*administration & dosage MH - Blood Transfusion MH - Double-Blind Method MH - Epistaxis/*drug therapy/etiology MH - Female MH - Humans MH - Male MH - Middle Aged MH - Quality of Life MH - Severity of Illness Index MH - Telangiectasia, Hereditary Hemorrhagic/*complications MH - Tranexamic Acid/administration & dosage MH - Treatment Outcome EDAT- 2016/09/07 06:00 MHDA- 2016/11/01 06:00 CRDT- 2016/09/07 06:00 PHST- 2016/09/07 06:00 [entrez] PHST- 2016/09/07 06:00 [pubmed] PHST- 2016/11/01 06:00 [medline] AID - 2547755 [pii] AID - 10.1001/jama.2016.11724 [doi] PST - ppublish SO - JAMA. 2016 Sep 6;316(9):943-51. doi: 10.1001/jama.2016.11724.