Title: Halting olfactory haemorrhage with Tranexamic acid in the Emergency Room
Funder: Department of Health and Social Care

Abstract: Background: Far from being trivial, epistaxis (nosebleed) can be fatal with over 60,000 UK Emergency Department (ED) attendances per year, resulting in over 20,000 emergency hospital admissions (>40,000 hospital bed days) each year. In one third of cases presenting to the ED, bleeding fails to settle with the simple measures described and patients undergo painful anterior nasal packing to control the haemorrhage5. This involves insertion of a firm nasal tampon measuring approximately 10-15 centimetres, which is painful for patients and has a 28% incidence of complications6. Tranexamic acid (TXA) is an inexpensive, safe treatment that prevents blood clot breakdown. Given intravenously, it reduces mortality following surgery and major trauma7. Applied topically after surgery, TXA reduces blood loss and the need for blood transfusion8. In epistaxis, a small trial with important methodological limitations suggested that topical TXA may reduce bleeding while improving patient satisfaction9. A well-designed randomised controlled trial is now urgently warranted to evaluate whether this simple treatment can reduce the need for anterior nasal packing and hospital admission. Aims: the aim of the study is to establish whether topical intranasal TXA may be used as an adjunct to standard therapy in patients presenting to the Emergency Department with spontaneous atraumatic epistaxis to reduce the need for anterior nasal packing compared to placebo. Secondary outcomes of the study are to assess the impact of the use of topical TXA on the need for hospital admission, the subsequent length of stay, need for blood products and the re-bleeding rate for patients subsequently discharged home. We will also monitor thrombotic complications as this is a potential side effect of TXA although this is considered a negligible risk with the low dose topical TXA used in this study. Research Question: in adult patients with acute spontaneous epistaxis does topical intranasal TXA used in addition to standard therapy reduce the need for intranasal packing? Plan of investigation: we plan to conduct a multi-centre randomised controlled trial comparing the use of TXA soaked on a cotton wool dental roll and inserted up the bleeding nostril to placebo. Adult patients presenting to the ED with epistaxis that persists after simple first aid, followed by 10 minutes of topical application of a vasoconstrictor (phenylephedrine) will be screened for eligibility. Eligible and consenting patients will have a soft dental roll soaked in 2mls of either TXA or placebo inserted into the external nasal orifice and held in place with gentle pinching of the nose for a further 10 minutes before removal. Patients will be assessed 2 minutes after its removal for continued bleeding, with the primary outcome being the need for subsequent anterior nasal packing. Secondary outcomes will be hospital admission, rebleeding, need for subsequent blood transfusion and thrombotic complications within 7 days. Potential benefits to patients and the NHS: Epistaxis represents a frequent ED presentation associated with significant morbidity and even mortality. Packing, whilst an effective method for controlling bleeding, is poorly tolerated, distressing and associated with significant complications. Application of topical intranasal TXA is an inexpensive procedure which, if effective, has the potential to provide better control of epistaxis, reduction in the need for packing and hence hospital admission. Thus, it has potential to be of real benefit to patients while reducing NHS costs.

Lay abstract: More than 60,000 people a year come to UK emergency departments with a spontaneous nosebleed1. The majority are elderly (aged over 70 years) and have heavy bleeding which has failed to stop with simple first aid measures (pinching the soft part of the nose with thumb and index finger, use of an ice pack on the nose and adopting a position leaning forward) either at home or from medically trained first responders (paramedics or ambulance technicians)2. However, these treatments do not always work and about a third of such patients need to have a pack or rigid dressing put up the nose that either swells up or is inflated to squash the bleeding vessel3. The most commonly used pack has similar size, shape and texture to a lollipop stick. Although packing usually works, it is an extremely uncomfortable and distressing procedure for most patients. Most patients who have had their nose packed stay in hospital on average for 2-3 days4. Packs are left in place for at least 24 hours, cause the sensation of a blocked nose and on-going discomfort and are often painful when taken out. Tranexamic acid (TXA) is a safe and cheap drug that can reduce bleeding by making blood clots less likely to be broken down by the body s natural pathways. In this study we plan to ask patients whose bleeding has not been stopped by simple routine measures if they would agree to be given an extra 10 minute treatment with soft cotton wool soaked in either TXA or water (to be decided by chance). Neither the doctor nor patient will know which study treatment has been used and afterwards patients will be treated according to usual care. The study will see whether using TXA resulted in fewer patients needing packing and hospital admission.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: BLOOD