Clinical trial NCT02638012
Conditions: Hereditary Hemorrhagic Telangiectasia (HHT) Epistaxis
Sponsor: Unity Health Toronto
Start date: 2015-12-01; Completion date: 2019-12-01
Enrollment: 8 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: Once the bleeding has stopped following application of the Floseal® a 50 cc syringe with sterile saline will be used to irrigate the treated nasal cavity to remove any excess Floseal® product as per manufacturer recommendations. This is done with the patient's head tilted downwards at a 30 degree angle so that the irrigation and excess product is removed from the nasal cavity.

If bleeding is not controlled after up to two Floseal applications, the gel and clots will be removed with suction, and the patient will be treated with a standard packing treatment (standard of care).
Interventions: intervention 1: Floseal intervention 2: Packing
Intervention descriptions: intervention 1: Topical lidocaine spray (2%) is then administered using 1-2 sprays in the affected nasal cavity via the nostril that is to have Floseal® applied. Once the bleeding has stopped following application of the Floseal® a 50 cc syringe with sterile saline will be used to irrigate the treated nasal cavity to remove any excess Floseal® product as per manufacturer recommendations. This is done with the patient's head tilted downwards at a 30 degree angle so that the irrigation and excess product is removed from the nasal cavity. Once the irrigation is complete, the nasal cavity is inspected for evidence of continued bleeding. intervention 2: If bleeding is not controlled after up to two Floseal applications, the gel and clots will be removed with suction, and the patient will be treated with a standard packing treatment (standard of care).

Protocol documents:
Prot_SAP_000.pdf: 
Prospective pilot study of Floseal® for the treatment of anterior epistaxis in patients with 
hereditary hemorrhagic telangiectasia (HHT) – Protocol and Statistical Analysis 
 
NCT02638012 
Date: April 30, 2020 
 
 


Patients afflicted with hereditary hemorrhagic telangiectasia (HHT) can suffer from frequent and 
heavy epistaxis, often requiring hospitalization for transfusions and surgical or endovascular 
procedures. As HHT patients represent a distinct group of individuals who are at increased risk 
of epistaxis, which has significant negative impact on QoL, evaluation within this specific group 
was warranted. Herein, we performed a pilot prospective clinical trial evaluating the efficacy of 
Floseal ® in managing acute epistaxis in HHT patients. 
 
Methods 
This multi-centered prospective clinical trial was registered with ClinicalTrials.gov 
(NCT02638012). Research ethics approval was received from both St. Michael’s Hospital and 
The Ottawa Hospital. 
 
Study population 
We aimed to recruit 10 patients, which is the sample size that is deemed appropriate for pilot 
studies. Patients 
age 18 and above with a documented diagnosis of HHT, and who were experiencing active 
anterior epistaxis were approached to voluntarily participate in this study. Patients were recruited 
after the Otolaryngology –Head and Neck Surgery service was consulted, eithe rthrough the 
Emergency Department, or from another in-patient service. Patients were excluded if they i) had 
aknown sensitivity to Floseal®, ii) had a known sensitivity to the topical medications 
administered as part of the evaluation and treatment of epistaxis (lidocaine, xylometazoline 
hydrochloride) or iii) were pregnant and/or breast feeding (the safety of Floseal® has not been 
established in pregnant women). 
 
Floseal® treatment 
The nasal cavity was suctioned, and the bleeding was visualized with anterior rhinoscopy. A total 
of 5 mL of Floseal ® (one standard preparation) was applied under direct visualization into the 
affected nasal cavity using the provided application catheter by a senior study investigator (JML 
or SK). Anterior nasal pressure was then applied for 5 min, and the nasal cavity was then 
reinspected 15 min after the initial application. In the event that bleeding was not controlled, an 
additional Floseal® application was to be applied. With failure to control bleeding with 2 
applications of Floseal® the protocol was to remove gel and clots with suction, and the patient 
was to be treated with a standard packing treatment (absorbable or non-absorbable) as standard 
of care. 
 
Outcome measures 
A patient-reported epistaxis questionnaire was administered as part of the study, and included the 
Epistaxis Severity 
Score (ESS). The survey is attached as part of Additional file 1. Modification to the ESS 
questionnaire included changes with regards to the timing (1 month, as compared to 3 months in 
the original ESS questionnaire). The patient-reported questionnaire was administered to all 
patients at the time of the Floseal® application (baseline), and at 1 month following treatment. 
Patients were also asked to report pain associated with application of Floseal®, rated on a visual-
analogue scale from 0 to 10, with 0 being “no pain”, and 10 being “worst pain in your life”. 
 


The primary outcome measures were achievement of hemostasis and changes in the ESS score 
between baseline and one-month follow up. Secondary outcome measures assessed subjective 
changes in epistaxis symptoms between baseline and follow up. Additionally, patients were 
reassessed clinically at 1 month follow up, capturing changes in telangiectasias, crusting, 
scarring, and active bleeding sites in the nasal cavity. Both sides of the nose were scored 
separately in each of these domains from 0 to 10, with 0 being “none” and 10 being “severe”. 
Clinical assessments were only performed by senior study investigators (JML and SK). The 
clinical assessment form is included as part of Additional file. 
 
Statistical analysis 
Descriptive statistics were used to summarize the frequency and percentage of categorical 
variables. Continuous variables were reported as mean and standard deviation. Paired t-test was 
performed to compare baseline and one month follow up differences in ESS, frequency of nose 
bleeds, and severity of nose bleeds. All statistical analyses were performed using Prism (v.7, 
GraphPad, USA), with significance set to α = 0.05.