Intranasal Bevacizumab for HHT-Related Epistaxis

NCT02389959 | Completed Phase 4 Results DMC

• 1 other identifier: 29501
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, controlled, double-blind, placebo-controlled trial of intranasal Avastin (bevacizumab) injection versus saline control for control of HHT-related epistaxis when used in conjunction with bipolar electrocautery.

Conditions

HHT; Hereditary Hemorrhagic Telangiectasia; Epistaxis; Nose Bleeds; Nasal Bleeding

Keywords

HHT; Hereditary Hemorrhagic Telangiectasia; epistaxis; nose bleeds; nasal bleeding; Avastin; bevacizumab

Outcome Measures

Primary Outcomes (1)

• Change in Epistaxis Severity Score (ESS)

  ESS is a standardized and reproducible outcome measure for the control of epistaxis. It is composed of six factors that are independent predictors of self-described epistaxis severity. The range is 0 to 13. The higher the score worse is epistaxis severity.

  Baseline and month 1, month 2, month 4, month 6

Secondary Outcomes (3)

• Short Form-12 (SF-12) Physical Component Summary (PCS) Score

  Baseline and month 1, month 2, month 4, month 6

• Short Form-12 (SF-12) Mental Component Summary (MCS) Score

  Baseline and month 1, month 2, month 4, month 6

• Reduction in Epistaxis-related Costs (Direct and Indirect)

  Baseline, Month 2, Month 6

Study Arms (2)

Bevacizumab

EXPERIMENTAL

The Stanford Hospital Investigational Pharmacy will perform all randomization, drug storage and management, as well as mixing and packaging for double-blinded injection of bevacizumab or saline control. Patients will undergo standard-of-care bipolar electrocautery of nasal telangiectasias in the Stanford Surgery Center operating room. At the time of electrocautery, patients will receive intranasal injection of either study drug or saline control. The surgeon performing the injection will be blinded to whether injection is composed of bevacizumab or saline control. Bevacizumab will be mixed by the Stanford Hospital Pharmacy to a total dose of 100mg in 4mL, and 50mg (2mL) will be injected into each side of the nose. Injections will be performed according to the standardized four-point injection protocol (0.5mL/site) based on the vascular anatomy of the nose published in 2012 by Dheyauldeen et al.

Drug: Bevacizumab

Saline Control

PLACEBO COMPARATOR

The Stanford Hospital Investigational Pharmacy will perform all randomization, drug storage and management, as well as mixing and packaging for double-blinded injection of bevacizumab or saline control. Patients will undergo standard-of-care bipolar electrocautery of nasal telangiectasias in the Stanford Surgery Center operating room. At the time of electrocautery, patients will receive intranasal injection of either study drug or saline control. The surgeon performing the injection will be blinded to whether injection is composed of bevacizumab or saline control. The saline control placebo will be mixed by the Stanford Hospital Pharmacy to a total dose of 4mL in order to be identical in quantity and appearance to the mixed doses of bevacizumab, and 2mL will be injected into each side of the nose. Injections will be performed according to the standardized four-point injection protocol (0.5mL/site) based on the vascular anatomy of the nose published in 2012 by Dheyauldeen et al.

Drug: Placebo (Saline)

Interventions

Bevacizumab DRUG

Bevacizumab will be mixed by the Stanford Hospital Pharmacy to a total dose of 100mg in 4mL, and 50mg (2mL) will be injected into each side of the nose

Also known as: Avastin

Bevacizumab

Placebo (Saline) DRUG

4mL of saline will be mixed by the Stanford Hospital Pharmacy as a control

Also known as: Salt water

Saline Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient carries a diagnosis of hereditary hemorrhagic telangiectasia (HHT)
• The patient is to undergo treatment with electrocautery in the operating room under endoscopic visualization
• The patient is able to give informed consent
• The patient is at least 18 years old

You may not qualify if:

• The patient has had prior treatment with systemic or nasal bevacizumab within the past year
• The patient has undergone electrocautery for epistaxis within the 6 months prior to study enrollment
• The patient is a minor
• The patient is pregnant
• The patient is incapable of understanding the consent process
• The patient has a history of HIV or another known cause of immunosuppression, or is actively taking immunosuppressive medications due to organ transplantation, rheumatoid disease, or other medical conditions.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University Department of Otolaryngology- Head and Neck Surgery

Stanford, California, 94305, United States

Location

Related Publications (18)

• Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, Kjeldsen AD, Plauchu H. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet. 2000 Mar 6;91(1):66-7. doi: 10.1002/(sici)1096-8628(20000306)91:13.0.co;2-p.

  PMID: 10751092 BACKGROUND

• Lund VJ, Howard DJ. A treatment algorithm for the management of epistaxis in hereditary hemorrhagic telangiectasia. Am J Rhinol. 1999 Jul-Aug;13(4):319-22. doi: 10.2500/105065899782102890.

  PMID: 10485021 BACKGROUND

• Sadick H, Riedel F, Naim R, Goessler U, Hormann K, Hafner M, Lux A. Patients with hereditary hemorrhagic telangiectasia have increased plasma levels of vascular endothelial growth factor and transforming growth factor-beta1 as well as high ALK1 tissue expression. Haematologica. 2005 Jun;90(6):818-28.

  PMID: 15951295 BACKGROUND

• Simonds J, Miller F, Mandel J, Davidson TM. The effect of bevacizumab (Avastin) treatment on epistaxis in hereditary hemorrhagic telangiectasia. Laryngoscope. 2009 May;119(5):988-92. doi: 10.1002/lary.20159.

  PMID: 19194865 BACKGROUND

• Karnezis TT, Davidson TM. Efficacy of intranasal Bevacizumab (Avastin) treatment in patients with hereditary hemorrhagic telangiectasia-associated epistaxis. Laryngoscope. 2011 Mar;121(3):636-8. doi: 10.1002/lary.21415. Epub 2010 Dec 16.

  PMID: 21344445 BACKGROUND

• Rohrmeier C, Sachs HG, Kuehnel TS. A retrospective analysis of low dose, intranasal injected bevacizumab (Avastin) in hereditary haemorrhagic telangiectasia. Eur Arch Otorhinolaryngol. 2012 Feb;269(2):531-6. doi: 10.1007/s00405-011-1721-9. Epub 2011 Jul 31.

  PMID: 21805356 BACKGROUND

• Chen S 4th, Karnezis T, Davidson TM. Safety of intranasal Bevacizumab (Avastin) treatment in patients with hereditary hemorrhagic telangiectasia-associated epistaxis. Laryngoscope. 2011 Mar;121(3):644-6. doi: 10.1002/lary.21345. Epub 2010 Nov 11.

  PMID: 21344447 BACKGROUND

• Dheyauldeen S, Ostertun Geirdal A, Osnes T, Vartdal LS, Dollner R. Bevacizumab in hereditary hemorrhagic telangiectasia-associated epistaxis: effectiveness of an injection protocol based on the vascular anatomy of the nose. Laryngoscope. 2012 Jun;122(6):1210-4. doi: 10.1002/lary.23303. Epub 2012 May 7.

  PMID: 22565282 BACKGROUND

• Karnezis TT, Davidson TM. Treatment of hereditary hemorrhagic telangiectasia with submucosal and topical bevacizumab therapy. Laryngoscope. 2012 Mar;122(3):495-7. doi: 10.1002/lary.22501. Epub 2011 Dec 6.

  PMID: 22147664 BACKGROUND

• Hoag JB, Terry P, Mitchell S, Reh D, Merlo CA. An epistaxis severity score for hereditary hemorrhagic telangiectasia. Laryngoscope. 2010 Apr;120(4):838-43. doi: 10.1002/lary.20818.

  PMID: 20087969 BACKGROUND

• Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992 Jun;30(6):473-83.

  PMID: 1593914 BACKGROUND

• Lennox PA, Hitchings AE, Lund VJ, Howard DJ. The SF-36 health status questionnaire in assessing patients with epistaxis secondary to hereditary hemorrhagic telangiectasia. Am J Rhinol. 2005 Jan-Feb;19(1):71-4.

  PMID: 15794078 BACKGROUND

• Ingrand I, Ingrand P, Gilbert-Dussardier B, Defossez G, Jouhet V, Migeot V, Dufour X, Klossek JM. Altered quality of life in Rendu-Osler-Weber disease related to recurrent epistaxis. Rhinology. 2011 Jun;49(2):155-62. doi: 10.4193/Rhino09.138.

  PMID: 21743869 BACKGROUND

• Steinbrook R. The price of sight--ranibizumab, bevacizumab, and the treatment of macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1409-12. doi: 10.1056/NEJMp068185. No abstract available.

  PMID: 17021315 BACKGROUND

• Smith KA, Rudmik L. Cost collection and analysis for health economic evaluation. Otolaryngol Head Neck Surg. 2013 Aug;149(2):192-9. doi: 10.1177/0194599813487850. Epub 2013 May 2.

  PMID: 23641023 BACKGROUND

• Koopmanschap MA. PRODISQ: a modular questionnaire on productivity and disease for economic evaluation studies. Expert Rev Pharmacoecon Outcomes Res. 2005 Feb;5(1):23-8. doi: 10.1586/14737167.5.1.23.

  PMID: 19807557 BACKGROUND

• Brazier J, Roberts J, Deverill M. The estimation of a preference-based measure of health from the SF-36. J Health Econ. 2002 Mar;21(2):271-92. doi: 10.1016/s0167-6296(01)00130-8.

  PMID: 11939242 BACKGROUND

• Brazier JE, Roberts J. The estimation of a preference-based measure of health from the SF-12. Med Care. 2004 Sep;42(9):851-9. doi: 10.1097/01.mlr.0000135827.18610.0d.

  PMID: 15319610 BACKGROUND

MeSH Terms

Conditions

Telangiectasia, Hereditary Hemorrhagic; Epistaxis

Interventions

Bevacizumab; Sodium Chloride; Fluoridation

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Telangiectasis; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Vascular Malformations; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Respiratory; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Preventive Dentistry; Dentistry; Public Health Dentistry; Environment and Public Health

Results Point of Contact

• Title: Peter H. Hwang, MD
• Organization: Stanford University

hwangph@stanford.edu

(650) 723-5281

Study Officials

• Peter H Hwang, MD

  Stanford University, Department of Otolaryngology- Head and Neck Surgery

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 11, 2015
• First Posted: March 17, 2015
• Study Start: August 4, 2014
• Primary Completion: January 23, 2020
• Study Completion: January 23, 2020
• Last Updated: September 1, 2021
• Results First Posted: February 15, 2021

Record last verified: 2021-08

Locations

US (1)