Effect of topical intranasal therapy on epistaxis frequency in patients with hereditary hemorrhagic telangiectasia: A randomized clinical trial

Kevin J. Whitehead, Nathan B. Sautter, Justin P. McWilliams, Murali M. Chakinala, Christian A. Merlo, Maribeth H Johnson, Melissa James, Eric M. Everett, Marianne S. Clancy, Marie E. Faughnan, S. Paul Oh, Scott E. Olitsky, Reed E. Pyeritz, James R Gossage

Research output: Contribution to journalArticle

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Abstract

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 HHTwas 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% (4mg/d), estriol 0.1% (0.4mg/d), tranexamic acid 10% (40mg/d), or placebo (0.9%saline). MAIN OUTCOMES AND MEASURES The primary outcomewas medianweekly 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.

Original languageEnglish (US)
Pages (from-to)943-951
Number of pages9
JournalJAMA - Journal of the American Medical Association
Volume316
Issue number9
DOIs
StatePublished - Jan 1 2016

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Hereditary Hemorrhagic Telangiectasia
Epistaxis
Randomized Controlled Trials
Tranexamic Acid
Estriol
Placebos
Therapeutics
Ferritins
Treatment Failure
Hospital Emergency Service
Hemoglobins
Emergency Treatment
Nose
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

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Effect of topical intranasal therapy on epistaxis frequency in patients with hereditary hemorrhagic telangiectasia : A randomized clinical trial. / Whitehead, Kevin J.; Sautter, Nathan B.; McWilliams, Justin P.; Chakinala, Murali M.; Merlo, Christian A.; Johnson, Maribeth H; James, Melissa; Everett, Eric M.; Clancy, Marianne S.; Faughnan, Marie E.; Oh, S. Paul; Olitsky, Scott E.; Pyeritz, Reed E.; Gossage, James R.

In: JAMA - Journal of the American Medical Association, Vol. 316, No. 9, 01.01.2016, p. 943-951.

Research output: Contribution to journalArticle

Whitehead, KJ, Sautter, NB, McWilliams, JP, Chakinala, MM, Merlo, CA, Johnson, MH, James, M, Everett, EM, Clancy, MS, Faughnan, ME, Oh, SP, Olitsky, SE, Pyeritz, RE & Gossage, JR 2016, 'Effect of topical intranasal therapy on epistaxis frequency in patients with hereditary hemorrhagic telangiectasia: A randomized clinical trial', JAMA - Journal of the American Medical Association, vol. 316, no. 9, pp. 943-951. https://doi.org/10.1001/jama.2016.11724
Whitehead, Kevin J. ; Sautter, Nathan B. ; McWilliams, Justin P. ; Chakinala, Murali M. ; Merlo, Christian A. ; Johnson, Maribeth H ; James, Melissa ; Everett, Eric M. ; Clancy, Marianne S. ; Faughnan, Marie E. ; Oh, S. Paul ; Olitsky, Scott E. ; Pyeritz, Reed E. ; Gossage, James R. / Effect of topical intranasal therapy on epistaxis frequency in patients with hereditary hemorrhagic telangiectasia : A randomized clinical trial. In: JAMA - Journal of the American Medical Association. 2016 ; Vol. 316, No. 9. pp. 943-951.
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abstract = "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 HHTwas 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{\%} (4mg/d), estriol 0.1{\%} (0.4mg/d), tranexamic acid 10{\%} (40mg/d), or placebo (0.9{\%}saline). MAIN OUTCOMES AND MEASURES The primary outcomewas medianweekly 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.",
author = "Whitehead, {Kevin J.} and Sautter, {Nathan B.} and McWilliams, {Justin P.} and Chakinala, {Murali M.} and Merlo, {Christian A.} and Johnson, {Maribeth H} and Melissa James and Everett, {Eric M.} and Clancy, {Marianne S.} and Faughnan, {Marie E.} and Oh, {S. Paul} and Olitsky, {Scott E.} and Pyeritz, {Reed E.} and Gossage, {James R}",
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TY - JOUR

T1 - Effect of topical intranasal therapy on epistaxis frequency in patients with hereditary hemorrhagic telangiectasia

T2 - A randomized clinical trial

AU - Whitehead, Kevin J.

AU - Sautter, Nathan B.

AU - McWilliams, Justin P.

AU - Chakinala, Murali M.

AU - Merlo, Christian A.

AU - Johnson, Maribeth H

AU - James, Melissa

AU - Everett, Eric M.

AU - Clancy, Marianne S.

AU - Faughnan, Marie E.

AU - Oh, S. Paul

AU - Olitsky, Scott E.

AU - Pyeritz, Reed E.

AU - Gossage, James R

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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 HHTwas 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% (4mg/d), estriol 0.1% (0.4mg/d), tranexamic acid 10% (40mg/d), or placebo (0.9%saline). MAIN OUTCOMES AND MEASURES The primary outcomewas medianweekly 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.

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 HHTwas 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% (4mg/d), estriol 0.1% (0.4mg/d), tranexamic acid 10% (40mg/d), or placebo (0.9%saline). MAIN OUTCOMES AND MEASURES The primary outcomewas medianweekly 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.

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