Topical Intranasal Tranexamic Acid for Epistaxis in the Emergency Department

• Sponsor: University of California, Davis (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02930941
• Collaborator: (none)
• Enrollment: 35
• Location: 1
• Arms: 2
• Duration (Months): 59
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

It is estimated that epistaxis results in 4.5 million emergency department visits per year throughout the United States. Due to the adverse effects of standard treatment options for epistaxis, tranexamic acid (TXA) may be considered an attractive option. In previous studies, when used with nasal packing, TXA showed faster time to control of bleeding. The goal of this study is to determine the efficacy and safety of topical intranasal TXA applied via atomizer for patients with epistaxis who present to the emergency department.

Condition or Disease	Intervention/Treatment	Phase
Epistaxis	Drug: Tranexamic Acid; Drug: 0.9% Sodium Chloride	Phase 4

Detailed Description

This is a prospective, randomized, single-center, double-blinded, placebo controlled study comparing efficacy and safety of topical intranasal tranexamic acid for epistaxis. The primary outcome was time to control of bleeding and secondary outcomes were length of stay in the emergency department, re-bleeding within the first 24 hours, and re-bleeding at one week. Safety outcomes were the incidence of thromboembolic events and other drug-related adverse events.

Patients aged 18 years of age or older and diagnosed with anterior epistaxis were included. Patients were excluded if they were unable to consent, do not have a valid telephone number, pregnant women, prisoners, cognitively impaired individuals, diagnosis of posterior epistaxis, major trauma, bleeding disorder (such as thrombocytopenia or hemophilia), hemodynamically unstable, or had a known hypersensitivity to study medication.

Patients were randomly assigned to tranexamic acid treatment group or placebo group. After consenting, patients received TXA (100 mg/1mL) or 0.9% sodium chloride (1 mL) in to the affected nostril(s) via intranasal atomization device. If bleeding did not cease, two repeat doses were allowed and after twenty minutes of continued bleeding the study physician could treat with any additional treatment options. Patients were contacted via telephone within one week to inquire about incidences of re-bleeding or any complications.

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Topical Intranasal Tranexamic Acid for Epistaxis in the Emergency Department
• Study Start Date: Feb 1, 2016
• Actual Primary Completion Date: Dec 31, 2020
• Actual Study Completion Date: Dec 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tranexamic Acid (100 mg/mL) TXA (100 mg/1mL) sprayed in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).	Drug: Tranexamic Acid; TXA (100 mg/1mL) in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).; Other Names: Cyklokapron
Placebo Comparator: 0.9% Sodium Chloride 0.9% Sodium Chloride (1mL) in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).	Drug: 0.9% Sodium Chloride; 0.9% Sodium Chloride (1mL) in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).; Other Names: Saline solution

Outcome Measures

Primary Outcome Measures

1. Time to Control of Bleeding (Minutes, Median, Interquartile Range) [During emergency department (ED) visit]

   Time to control of bleeding was defined as the time from the start of enrollment and direct pressure and administration of study drug to the resolution of bleeding

Secondary Outcome Measures

1. Length of Stay in the Emergency Department (Minutes, Median, Inter-Quartile Range) [During emergency department (ED) visit]

   Length of stay was defined as time from enrollment in study to discharge from the emergency department

2. Number of Participants With Re-bleeding at 24 Hours [24 hours]

   The number of participants with re-bleeding at 24 Hours was evaluated during follow up phone call

3. Number of Participants With Re-bleeding at One Week [7 days]

   The number of participants with re-bleeding at one week was evaluated during the follow-up phone call

4. Thromboembolism [7 days]

   Patient reported thromboembolic events during follow-up phone calls at 24 hours and at one week

5. Drug-Related Adverse Events [during emergency department (ED) visit]

   Patient-reported drug-related adverse events during ED visit

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosed with anterior epistaxis

Exclusion Criteria:

• Unable to consent, do not have a valid telephone number, pregnant women, prisoners, cognitively impaired individuals, diagnosis of posterior epistaxis, major trauma, bleeding disorder (such as thrombocytopenia or hemophilia), hemodynamically unstable, or had a known hypersensitivity to study medication

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Davis Medical Center	Sacramento	California	United States	95817

Sponsors and Collaborators

• University of California, Davis

Investigators

• Principal Investigator: Aimee Moulin, MD, University of California, Davis

Study Documents (Full-Text)

• Study Protocol and Informed Consent Form - Feb 6, 2017
• Statistical Analysis Plan - Feb 6, 2017

More Information

Publications

• Aguilera X, Martínez-Zapata MJ, Hinarejos P, Jordán M, Leal J, González JC, Monllau JC, Celaya F, Rodríguez-Arias A, Fernández JA, Pelfort X, Puig-Verdie Ll. Topical and intravenous tranexamic acid reduce blood loss compared to routine hemostasis in total knee arthroplasty: a multicenter, randomized, controlled trial. Arch Orthop Trauma Surg. 2015 Jul;135(7):1017-25. doi: 10.1007/s00402-015-2232-8. Epub 2015 May 7.
• Akkan S, Çorbacıoğlu ŞK, Aytar H, Emektar E, Dağar S, Çevik Y. Evaluating Effectiveness of Nasal Compression With Tranexamic Acid Compared With Simple Nasal Compression and Merocel Packing: A Randomized Controlled Trial. Ann Emerg Med. 2019 Jul;74(1):72-78. doi: 10.1016/j.annemergmed.2019.03.030. Epub 2019 May 9.
• Dunn CJ, Goa KL. Tranexamic acid: a review of its use in surgery and other indications. Drugs. 1999 Jun;57(6):1005-32. Review.
• Klepfish A, Berrebi A, Schattner A. Intranasal tranexamic acid treatment for severe epistaxis in hereditary hemorrhagic telangiectasia. Arch Intern Med. 2001 Mar 12;161(5):767.
• Kucik CJ, Clenney T. Management of epistaxis. Am Fam Physician. 2005 Jan 15;71(2):305-11. Review.
• Morgan DJ, Kellerman R. Epistaxis: evaluation and treatment. Prim Care. 2014 Mar;41(1):63-73. doi: 10.1016/j.pop.2013.10.007. Review.
• Pallin DJ, Chng YM, McKay MP, Emond JA, Pelletier AJ, Camargo CA Jr. Epidemiology of epistaxis in US emergency departments, 1992 to 2001. Ann Emerg Med. 2005 Jul;46(1):77-81.
• Reuben A, Appelboam A, Stevens KN, Vickery J, Ewings P, Ingram W, Jeffery AN, Body R, Hilton M, Coppell J, Wainman B, Barton A. The Use of Tranexamic Acid to Reduce the Need for Nasal Packing in Epistaxis (NoPAC): Randomized Controlled Trial. Ann Emerg Med. 2021 Jun;77(6):631-640. doi: 10.1016/j.annemergmed.2020.12.013. Epub 2021 Feb 19.
• Singer AJ, Blanda M, Cronin K, LoGiudice-Khwaja M, Gulla J, Bradshaw J, Katz A. Comparison of nasal tampons for the treatment of epistaxis in the emergency department: a randomized controlled trial. Ann Emerg Med. 2005 Feb;45(2):134-9.
• Tibbelin A, Aust R, Bende M, Holgersson M, Petruson B, Rundcrantz H, Alander U. Effect of local tranexamic acid gel in the treatment of epistaxis. ORL J Otorhinolaryngol Relat Spec. 1995 Jul-Aug;57(4):207-9.
• Utkewicz MD, Brunetti L, Awad NI. Epistaxis complicated by rivaroxaban managed with topical tranexamic acid. Am J Emerg Med. 2015 Sep;33(9):1329.e5-7. doi: 10.1016/j.ajem.2015.02.049. Epub 2015 Mar 6.
• Villwock JA, Jones K. Recent trends in epistaxis management in the United States: 2008-2010. JAMA Otolaryngol Head Neck Surg. 2013 Dec;139(12):1279-84. doi: 10.1001/jamaoto.2013.5220. Review.
• Waldow T, Szlapka M, Haferkorn M, Bürger L, Plötze K, Matschke K. Prospective clinical trial on dosage optimizing of tranexamic acid in non-emergency cardiac surgery procedures. Clin Hemorheol Microcirc. 2013 Jan 1;55(4):457-68. doi: 10.3233/CH-131782.
• White A, O'Reilly BF. Oral tranexamic acid in the management of epistaxis. Clin Otolaryngol Allied Sci. 1988 Feb;13(1):11-6.
• Wolfe TR, Braude DA. Intranasal medication delivery for children: a brief review and update. Pediatrics. 2010 Sep;126(3):532-7. doi: 10.1542/peds.2010-0616. Epub 2010 Aug 9. Review.
• Zahed R, Moharamzadeh P, Alizadeharasi S, Ghasemi A, Saeedi M. A new and rapid method for epistaxis treatment using injectable form of tranexamic acid topically: a randomized controlled trial. Am J Emerg Med. 2013 Sep;31(9):1389-92. doi: 10.1016/j.ajem.2013.06.043. Epub 2013 Jul 30.

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT02930941
• Other Study ID Numbers: 844609
• First Posted: Oct 12, 2016
• Last Update Posted: Nov 30, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Keywords provided by University of California, Davis: tranexamic acid; epistaxis; emergency medicine; intranasal; TXA
• Additional relevant MeSH terms: Epistaxis; Emergencies; Tranexamic Acid

Study Results

Participant Flow

Arm/Group Title	Tranexamic Acid (100 mg/mL)	0.9% Sodium Chloride
Arm/Group Description	TXA (100 mg/1mL) sprayed in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s). Tranexamic Acid: TXA (100 mg/1mL) in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).	0.9% Sodium Chloride (1mL) in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s). 0.9% Sodium Chloride: 0.9% Sodium Chloride (1mL) in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).
Period Title: Overall Study
STARTED	17	18
COMPLETED	16	16
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	TXA Group	NS Group	Total
Arm/Group Description	Patients that received tranexamic (TXA)(100 mg/1mL) sprayed in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).	Patients that received 0.9% Sodium Chloride (NS) (1mL) in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).	Total of all reporting groups
Overall Participants	17	18	35
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	7 41.2%	9 50%	16 45.7%
>=65 years	10 58.8%	9 50%	19 54.3%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	61	62	62
Sex: Female, Male (Count of Participants)
Female	6 35.3%	12 66.7%	18 51.4%
Male	11 64.7%	6 33.3%	17 48.6%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	17 100%	18 100%	35 100%
Past Medical History (Count of Participants)
Anemia	1 5.9%	1 5.6%	2 5.7%
Atrial Fbrillation or flutter	4 23.5%	2 11.1%	6 17.1%
Cancer	2 11.8%	2 11.1%	4 11.4%
Chronic Kidney Disease	5 29.4%	2 11.1%	7 20%
Congestive Heart Failure	4 23.5%	1 5.6%	5 14.3%
Diabetes	4 23.5%	6 33.3%	10 28.6%
Hyperlipidemia	5 29.4%	5 27.8%	10 28.6%
Ischemic Stroke	1 5.9%	0 0%	1 2.9%
Obesity	2 11.8%	0 0%	2 5.7%
Pulmonary Embolism	0 0%	1 5.6%	1 2.9%
Deep Vein Thrombosis	0 0%	1 5.6%	1 2.9%
Myocardial infarction	1 5.9%	0 0%	1 2.9%
Coronary Artery Bypass	1 5.9%	1 5.6%	2 5.7%
Hypertension	11 64.7%	7 38.9%	18 51.4%
Antiplatelet (Count of Participants)
Aspirin	8 47.1%	2 11.1%	10 28.6%
Clopidogrel	2 11.8%	1 5.6%	3 8.6%
Prasugrel	1 5.9%	0 0%	1 2.9%
Ticagrelor	1 5.9%	0 0%	1 2.9%
Anticoagulation (Count of Participants)
Warfarin	4 23.5%	2 11.1%	6 17.1%
Apixaban	3 17.6%	2 11.1%	5 14.3%
Rivaroxaban	0 0%	0 0%	0 0%
Dabigatran	0 0%	0 0%	0 0%
Hemoglobin (g/dL) [Mean (Full Range) ]
Mean (Full Range) [g/dL]	12.9	12	12.4
Hematocrit (% by volume of hemoglobin in blood) [Mean (Full Range) ]
Mean (Full Range) [% by volume of hemoglobin in blood]	38	35.8	36.9
Platelet (x10^3 per microliter) [Mean (Full Range) ]
Mean (Full Range) [x10^3 per microliter]	210.1	248	229.8

Outcome Measures

1. Primary Outcome

Title	Time to Control of Bleeding (Minutes, Median, Interquartile Range)
Description	Time to control of bleeding was defined as the time from the start of enrollment and direct pressure and administration of study drug to the resolution of bleeding
Time Frame	During emergency department (ED) visit

Outcome Measure Data

Analysis Population Description

Intention-to-treat

Arm/Group Title	TXA Group	NS Group
Arm/Group Description	Tranexamic (TXA)(100 mg/1mL) sprayed in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).	0.9% Sodium Chloride (NS) (1mL) in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).
Measure Participants	17	18
Median (Inter-Quartile Range) [minutes]	64	42

2. Secondary Outcome

Title	Length of Stay in the Emergency Department (Minutes, Median, Inter-Quartile Range)
Description	Length of stay was defined as time from enrollment in study to discharge from the emergency department
Time Frame	During emergency department (ED) visit

Outcome Measure Data

Analysis Population Description

Intention to treat

Arm/Group Title	TXA Group	NS Group
Arm/Group Description	Tranexamic (TXA)(100 mg/1mL) sprayed in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).	0.9% Sodium Chloride (NS) (1mL) in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).
Measure Participants	17	18
Median (Inter-Quartile Range) [minutes]	268	346

3. Secondary Outcome

Title	Number of Participants With Re-bleeding at 24 Hours
Description	The number of participants with re-bleeding at 24 Hours was evaluated during follow up phone call
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Intention to treat. Lost to follow up: 1 in TXA group and 1 in NS group

Arm/Group Title	TXA Group	NS Group
Arm/Group Description	Tranexamic group	Normal saline
Measure Participants	16	17
Count of Participants [Participants]	3 17.6%	9 50%

4. Secondary Outcome

Title	Number of Participants With Re-bleeding at One Week
Description	The number of participants with re-bleeding at one week was evaluated during the follow-up phone call
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

Intention-to-treat. Loss to follow-up: 1 in TXA group and 2 in NS group

Arm/Group Title	TXA Group	NS Group
Arm/Group Description	Patients that received tranexamic (TXA)(100 mg/1mL) sprayed in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).	Patients that received 0.9% Sodium Chloride (NS) (1mL) in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).
Measure Participants	16	16
Count of Participants [Participants]	2 11.8%	6 33.3%

5. Secondary Outcome

Title	Thromboembolism
Description	Patient reported thromboembolic events during follow-up phone calls at 24 hours and at one week
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

Intention to treat. Lost to follow up of 1 in TXA group and 2 in NS group.

Arm/Group Title	TXA Group	NS Group
Arm/Group Description	Patients that received tranexamic (TXA)(100 mg/1mL) sprayed in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).	Patients that received 0.9% Sodium Chloride (NS) (1mL) in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).
Measure Participants	16	16
Count of Participants [Participants]	0 0%	0 0%

6. Secondary Outcome

Title	Drug-Related Adverse Events
Description	Patient-reported drug-related adverse events during ED visit
Time Frame	during emergency department (ED) visit

Outcome Measure Data

Analysis Population Description

Intention to treat

Arm/Group Title	TXA Group	NS Group
Arm/Group Description	Patients that received tranexamic (TXA)(100 mg/1mL) sprayed in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).	Patients that received 0.9% Sodium Chloride (NS) (1mL) in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).
Measure Participants	17	18
Nasal burning	2 11.8%	0 0%
Nasal irritation	0 0%	0 0%
Unpleasant taste	1 5.9%	0 0%

Adverse Events

Time Frame	One week from initial ED visit
Adverse Event Reporting Description	All adverse effects reported from patients were collected. Mortality was not collected beyond 7 days.
Arm/Group Title	TXA Group		NS Group
Arm/Group Description	Patients that received tranexamic (TXA)(100 mg/1mL) sprayed in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).		Patients that received 0.9% Sodium Chloride (NS) (1mL) in to the affected nostril(s) via intranasal atomization device. May repeat 2 doses in each affected nostril(s).
All Cause Mortality
	TXA Group		NS Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/18 (0%)
Serious Adverse Events
	TXA Group		NS Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	TXA Group		NS Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/17 (23.5%)		0/18 (0%)
Gastrointestinal disorders
Rhinorrhea	1/17 (5.9%)	1	0/18 (0%)	0
General disorders
Nasal Burning	2/17 (11.8%)	2	0/18 (0%)	0
Unpleasant taste	1/17 (5.9%)	1	0/18 (0%)	0

Limitations/Caveats

Coronavirus Disease 2019 (COVID-19) pandemic significantly impacted the ability to enroll patients; early termination leading to a small number of patients; single-center study;

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.