Clinical trial NCT02638012: Prospective Pilot Study of Floseal for the Treatment of Anterior Epistaxis in Patients With (HHT)
Official title: Prospective Pilot Study of Floseal for the Treatment of Anterior Epistaxis in Patients With Hereditary Hemorrhagic Telangiectasia (HHT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hereditary Hemorrhagic Telangiectasia (HHT)
Epistaxis
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
Collaborators: name: The Ottawa Hospital
First posted: 2015-12-22
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Current management strategies for severe and recurrent epistaxis secondary to Hereditary hemorrhagic telangiectasia (HHT) include surgical procedures, and uncomfortable nasal packing, both of which are often only short-term solutions. Floseal® may provide a non-invasive and less painful treatment option for epistaxis in HHT patients. This hemostatic agent has been shown to be an effective intraoperative hemostatic agent in a number of surgical procedures including endoscopic sinus surgery. It has also been shown to be favorable over nasal packing at controlling acute anterior epistaxis. Though the efficacy of using Floseal® for epistaxis in HHT patients has been proven anecdotally in the literature it has yet to be proven in a prospective clinical trial. The results of this pilot study will provide insight into the efficacy of using Floseal® in the management of severe epistaxis in HHT patients and to assist in the development of a full-scale prospective clinical trial.

Detailed description: Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is an autosomal dominant disorder that is characterized by abnormal blood vessel development. This dysplasia manifests as mucocutaneous telangiectases and visceral arteriovenous malformations (AVM).

The most common symptom is epistaxis occurring secondary to telangiectases in the nasal mucosa in more than 90% of HHT patients. Heterogeneity exists in the severity of epistaxis experienced by HHT patients; therefore, treatments and management strategies can vary. For minor bleeding, conservative management may include preventing drying of the nasal mucosa with the use of ointments and humidification. In some cases, topical or systemic estrogen may also be used to improve the stability of the nasal mucosa, thereby reducing bleeding. Commonly, anterior nasal packing is used as a non-surgical management strategy to control major bleeding. When medical management strategies have failed, laser coagulation of the telangiectases or septodermoplasty may be considered however, these solutions are temporary as telangiectasia are known to recur. In the acute setting, embolization may be used to occlude the abnormal vasculature while maintaining blood flow to the surrounding tissue; however, this is also not an effective long-term solution. Severe and difficult to manage epistaxis has been effectively treated using the modified Young's procedure where closure of the nostril is achieved by suturing together circumferential skin and mucosa flaps.

Floseal hemostatic matrix (Floseal®) is a hemostatic agent that consists of two major components. The first are gelatin granules that swell when they come into contact with blood or other wet surfaces creating a tamponade effect. The second is a high concentration of human thrombin that promotes natural clot formation by converting fibrinogen to fibrin. Floseal® is hydrophilic and therefore adheres well to wet tissues. It is indicated for use as an adjunct surgical hemostat and it has recently been demonstrated to be an effective treatment for epistaxis. A prospective, randomized, controlled trial compared Floseal® to nasal packing in the treatment of acute anterior epistaxis. The results showed Floseal® to be better at initially controlling epistaxis and resulted in fewer rebleed events within a seven day follow-up period. Patients also reported less pain and greater overall satisfaction with Floseal® as compared with nasal packing. Similarly, two prospective studies have evaluated the use of Floseal® for the treatment of posterior epistaxis. These trials also showed Floseal® treatment to be an effective treatment for posterior epistaxis. Furthermore, the use of Floseal® was associated with substantial institutional cost savings.

In summary, Floseal® has been demonstrated to be an effective treatment for posterior epistaxis, regardless of origin within the nose. Recently, Floseal® has been used in patients with HHT. This case series showed that patients with anterior epistaxis due to HHT could self-administer Floseal® to treat recurrent anterior epistaxis at their home without a contact with the medical system, as would customarily occur. This directly leads to an improvement in the quality of life of the patients in this study. Impairment of the quality of life for patients with HHT is a significant concern. Compared to the normative population, all subscales of SF36, but bodily pain, have been shown to be significantly poorer in the HHT patients. Studies of HHT substantiate that disease severity is associated with poorer QoL in these patients. Treatments for epistaxis that can improve the quality of life for patients with HHT are needed.

Eligibility criteria: Inclusion Criteria:

* Documented diagnosis of HHT
* Active anterior epistaxis

Exclusion Criteria:

* A known sensitivity to any of the materials of Floseal® or the topical medications administered as part of the evaluation and treatment of epistaxis (lidocaine, xylometazoline hydrochloride)
* Pregnant and/or breast feeding woman

Primary outcomes:
measure: Epistaxis Severity Score (ESS)
timeFrame: Baseline and 1 month
Secondary outcomes:
measure: Change in Number of Nose Bleeds During One Month Period Following Treatment
timeFrame: Baseline and 1 month
measure: Change in Severity Rating of Nose Bleeds During One Month Period Following Treatment
timeFrame: Baseline and 1 month
measure: Change in Need for Additional Interventions to Control Epistaxis During One Month Following Floseal® Application
timeFrame: Baseline and 1 month
measure: Change in Clinical Assessment of Telangiectases, Crusting, Scarring, and Active Bleeding Sites in the Nasal Cavity Before and One Month Following Treatment
timeFrame: Baseline and 1 month
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
Study officials:
affiliation: Unity Health Toronto
name: John Lee, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sharathkumar AA, Shapiro A. Hereditary haemorrhagic telangiectasia. Haemophilia. 2008 Nov;14(6):1269-80. doi: 10.1111/j.1365-2516.2008.01774.x.
citation: Olitsky SE. Hereditary hemorrhagic telangiectasia: diagnosis and management. Am Fam Physician. 2010 Oct 1;82(7):785-90.
citation: Pau H, Carney AS, Murty GE. Hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): otorhinolaryngological manifestations. Clin Otolaryngol Allied Sci. 2001 Apr;26(2):93-8. doi: 10.1046/j.1365-2273.2001.00442.x.
citation: Mathiasen RA, Cruz RM. Prospective, randomized, controlled clinical trial of a novel matrix hemostatic sealant in patients with acute anterior epistaxis. Laryngoscope. 2005 May;115(5):899-902. doi: 10.1097/01.MLG.0000160528.50017.3C.
citation: 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.
citation: Kilty SJ, Al-Hajry M, Al-Mutairi D, Bonaparte JP, Duval M, Hwang E, Tse D. Prospective clinical trial of gelatin-thrombin matrix as first line treatment of posterior epistaxis. Laryngoscope. 2014 Jan;124(1):38-42. doi: 10.1002/lary.24240. Epub 2013 Jun 28.
citation: Warner L, Halliday J, James K, de Carpentier J. Domiciliary floseal prevents admission for epistaxis in hereditary hemorrhagic telangiectasia. Laryngoscope. 2014 Oct;124(10):2238-40. doi: 10.1002/lary.24701. Epub 2014 May 2. No abstract available.
citation: Geirdal AO, Dheyauldeen S, Bachmann-Harildstad G, Heimdal K. Quality of life in patients with hereditary hemorrhagic telangiectasia in Norway: a population based study. Am J Med Genet A. 2012 Jun;158A(6):1269-78. doi: 10.1002/ajmg.a.35309. Epub 2012 Apr 23.
citation: Geisthoff UW, Heckmann K, D'Amelio R, Grunewald S, Knobber D, Falkai P, Konig J. Health-related quality of life in hereditary hemorrhagic telangiectasia. Otolaryngol Head Neck Surg. 2007 May;136(5):726-33; discussion 734-5. doi: 10.1016/j.otohns.2006.12.019.
citation: Jameson M, Gross CW, Kountakis SE. FloSeal use in endoscopic sinus surgery: effect on postoperative bleeding and synechiae formation. Am J Otolaryngol. 2006 Mar-Apr;27(2):86-90. doi: 10.1016/j.amjoto.2005.07.011.
citation: Lee JM, Wu V, Faughnan ME, Lasso A, Figol A, Kilty SJ. Prospective pilot study of Floseal(R) for the treatment of anterior epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT). J Otolaryngol Head Neck Surg. 2019 Oct 15;48(1):48. doi: 10.1186/s40463-019-0379-y.