2. The Use of Tranexamic Acid to Reduce the Need for Nasal
Packing in Epistaxis (NoPAC): Randomized Controlled Trial
3. Reuben A, Appelboam A, Stevens KN, Vickery J, Ewings P,
Ingram W et al. The Use of Tranexamic Acid to Reduce the
Need for Nasal Packing in Epistaxis (NoPAC): Randomized
Controlled Trial. Ann Emerg Med. 2021 ;77(6):631-640.
doi: 10.1016/j.annemergmed.2020.12.013.
Epub 2021 Feb 19.
PMID: 33612282.
4. Introductory Background
Epistaxis is an extremely common medical condition,
- accounts for up to 1 in 200 emergency department (ED)
presentations in the United States and,
- in one ED in the United Kingdom, an estimated 100 per
100,000 presentations per year.
- Patients seeking medical attention are frequently elderly and
men.
5. Introductory Background
• In most cases, epistaxis resolves with simple measures like
firm pressure with the thumb and index finger to the soft
anterior part of the nose, the use of ice packs on the bridge of
the nose and adopting a forward leaning posture.
• Current approaches to managing epistaxis in the emergency
department (ED) beyond simple first aid include the use of
topical vasoconstrictors, which have been shown to arrest
bleeding in up to 65% of patients.
6. Introductory Background
• Patients presenting to EDs with epistaxis uncontrolled by
subsequent simple first aid measures or application of topical
vasoconstrictors will typically undergo anterior nasal
packing.
• Anterior nasal packing is an effective method of controlling
persistent bleeding, leading to cessation in up to 85% of
cases.
6
7. Introductory Background
• Packing is effective, but can be painful and unpleasant and
patients usually need hospital admission. Nasal packs
typically remain in situ for at least 24hours, which causes
ongoing pain and an uncomfortable nasal obstruction.
Removal is also painful.
• Nasal packing is associated with a complication rate of up to
28%. (infection, toxic shock syndrome, hypoxia, sleep
apnoea, pack displacement with airway obstruction and
bleeding on removal.)
8. Introductory Background
• Tranexamic acid (TXA) is an antifibrinolytic agent which
acts by competitively binding to plasminogen and plasmin in
circulating blood at the site of injury, reducing the production
and action of plasmin.
• TXA may be used via the intravenous or oral routes, having
systemic action, or topically, where its effects are very
localised, acting on the mucosa/blood vessels with which it is
in contact.
9. Introductory Background
• Large-scale trials have demonstrated TXA to be safe and to reduce
blood loss after surgery when applied topically.
• Studies on the use of topical intranasal TXA in epistaxis,seem to
favor its use, but the studies are variable in their methodology, with
small sample sizes.
• If topical tranexamic acid is an effective treatment for epistaxis that
fails to resolve with simple measures, it could reduce the need for
nasal packing and subsequent hospital admission.
10. Primary objective of the study
-To test the effectiveness of topical intranasal tranexamic acid
in reducing the need for anterior nasal packing in adult patients
presenting to the ED with spontaneous atraumatic epistaxis in
a UK ED setting.
11. Secondary objectives:
-Need for anterior nasal packing during the index ED visit or
after 7 days’ follow-up,
-Hospital admission and subsequent length of hospital stay,
-Requirement for blood products, rebleeding rate, and
-Any adverse events, including thrombotic complications.
12. Materials & Methods
• 1:1, block-randomized, double-blind, parallel-group, placebo-
controlled trial in 26 centers with type 1 EDs across the
United Kingdom
• Patients older than 18 years presenting to the ED with
persistent epistaxis were eligible for the study.
• Persistent epistaxis was defined as the continued presence of
blood on the upper lip after wiping, emanating from the
nares.
12
13. Materials & Methods
Exclusion Criteria:
-Patients demonstrating hemodynamic instability,
-epistaxis occurring as a result of trauma,
-with out-of-hospital packing,
-documented allergy to tranexamic acid, or
-"expected” by the ear, nose, and throat in-patient team for
specialist treatment .
14. Materials & Methods
Other exclusion criteria
-known or suspected nasopharyngeal malignancy,
-previous inclusion in the study,
-pregnancy,
-hemophilia,
-inability or unwillingness to provide consent.
Because eligible participants presenting to the ED with
epistaxis
were not randomly selected for the study, the participants
15. Sample size calculation :
Assumption: Patients with persistent epistaxis, in which simple
measures and vasoconstrictors fail to control the bleeding, will
need nasal packing.Majority of patients (95%) would require
packing.
The study aimed to detect a 10% absolute reduction in packing
rate, which was the minimum for improvement in clinical
practice.
16. Sample size calculation :
This difference required 207 patients per group,
• assuming a corrected chi squared test result powered at 90%
and
• with a significance level of 5%.
The total recruitment target was 450 to allow any subsequent
loss to follow-up.
17.
18.
19. Consenting participants were given the treatment contained
within the next sequentially numbered pack.
The packs contained a sealed vial of the trial solution (TXA or
matched placebo), as well as 2 dental rolls.
Treating clinicians and participants were blinded to the
treatment allocation.
20. The intervention was TXA for topical (intranasal) use, prepared as a
clear, colorless solution at 100 mg/mL. The comparator (placebo) was
sterile water.
Both were provided in identical glass vials.
Trial treatment consisted of 4 mL of tranexamic acid or placebo, given
in up to 2 divided doses of 2 mL.
A 9X9 mm cotton wool dental roll soaked in approximately half of the
trial solution was gently inserted into the bleeding nostril .Dental roll
was held in place with a disposable nasal clip and left in situ for 10
minutes.
21. When epistaxis persisted, a second trial treatment (the
remaining 2 mL of trial solution) was applied in the same
manner, on a second dental roll held in place with a nasal clip.
Participants therefore received a topical application of either
200 or 400 mg of tranexamic acid, or placebo.
24. Results
• During the index ED attendance, 211 participants (42.5%)
received anterior nasal packing for epistaxis. Of participants
allocated to receive TXA, 111 (43.7%) underwent packing in
the ED compared with 100 (41.3%) in the placebo group.
• There was no statistically significant difference in the rate of
anterior nasal packing between allocated groups, with an
odds ratio of 1.11 (95% confidence interval 0.77 to 1.59)
from the primary analysis.
24
26. ARE THE RESULTS OF THE STUDY VALID?
1. Was the assignment of patients to
treatment randomized?
[ √] Yes [ ] No [ ] Can't Tell
27. Pragmatic, 1:1, block-randomized, double-blind, parallel-
group, placebo-controlled trial in 26 centers with type 1 EDs
across the United Kingdom between May 5, 2017, and March
31,2019.
28. A type 1 ED is defined as “a consultant led 24-hour service
with full resuscitation facilities and designated accommodation
for the reception of accident and emergency patients.
29. ARE THE RESULTS OF THE STUDY VALID?
Were all patients who entered the trial properly accounted for
and attributed at its conclusion?
[√ ] Yes
• Was follow-up complete?
From direct patient contact, scrutiny of the hospital notes, or both,
follow-up data were available for all 496 patients recruited.
• Were patients analyzed in the groups to which they were
randomized (intention to treat analysis)?
Yes
30. ARE THE RESULTS OF THE STUDY VALID?
3. Were patients, their clinicians, and study personnel 'blind'
to treatment?
[√ ] Yes
31. • This is a double-blind study as neither the research teams
responsible for treating and assessing patients within this trial
nor the participants themselves are aware of individual
treatment allocations.
• Should the clinical need arise, a procedure was in place to
enable emergency unblinding of treatment allocation.
32. ARE THE RESULTS OF THE STUDY VALID?
4. Were the groups similar at the start of the trial?
[√ ] Yes
• Baseline prognostic factors (demographics, co-morditity,
disease severity, other known confounders) balanced?
YES.
33. Characteristic Placebo
(Mean±SD)
N=242
TXA
(Mean±SD)
N=254
Age in years 72.3(13.9) 70.1(15.6)
Systolic Blood Pressure(mmHg) 150.7(25.8) 150.2(27.9)
Diastolic Blood Pressure(mmHg) 87(15.3) 85.8(18.4)
Pulse Rate(bpm) 82.2(16.6) 82.6(17.2)
Patient characteristics
35. ARE THE RESULTS OF THE STUDY VALID?
5. Aside from the experimental intervention, were the groups
treated equally?
[ √] Yes
• There was no co-intervention.
• There was no contamination with the data.
• Compliance from the multicentric study groups was present.
36. WHAT WERE THE RESULTS?
1. How large was the treatment effect?
[ ] Yes [ ] No [ √] Can't Tell
37. WHAT WERE THE RESULTS?
How precise was the estimate of the treatment effect?
• Confidence intervals?
There was no statistically significant difference in the rate of
anterior nasal packing between allocated groups, with an
odds ratio of 1.11 (95% confidence interval 0.77 to 1.59)
from the primary analysis.
38. WILL THE RESULTS HELP ME
IN CARING FOR MY PATIENTS?
1. Can the results be applied to my patient care?
[ ] Yes [ ] No [ ] Can't Tell
• Patients similar for demographics, severity, co-morbidity and
other prognostic factors?
• Compelling reason why the results should not be applied?
39. WILL THE RESULTS HELP ME
IN CARING FOR MY PATIENTS?
2. Were all clinically important outcomes considered?
[ √] Yes
• Are substitute endpoints valid? YES.
40. WILL THE RESULTS HELP ME
IN CARING FOR MY PATIENTS?
3. Are the likely treatment benefits worth the potential harms
and costs?
[ √] Yes
41. Strengths of the study
Largest single study to date to investigate the role of topical
intranasal tranexamic acid as an adjunct to standard therapy for
patients with spontaneous epistaxis.
42. Strengths of the study
• Data collected from 26 ED s from UK with a standardised
protocol.
• It has reinforced the safety of local application of TXA to
control bleeding.Of 200mg applied to a dry dental roll, a
maximum of 39.8mg (Mean of 14mg)is absorbed
systemically.
43. Strengths of the study
• Anterior nasal packing was used as the primary outcome
measure, in stead of bleeding cessation ,as done in previous
studies.
44. Strengths of the study
• Follow-up data were available for all 496 patients recruited.
The availability of follow-up data for 100% of patients
recruited and the rigor of the methodology bolster confidence
about the real-world accuracy of the results.
45. Weakness of the study
1.Sample size calculation - based on a predicted anterior nasal
packing rate of 95% for patients for whom standard treatment
had failed .
The packing rate in the study did not meet this percentage:
41.3% of patients received packing in the Placebo group
compared with 43.7% in theTXA group. Therefore, the study
may have been underpowered.
46. Weakness of the study
2. Participants included in this study were a convenience
sample and could be subject to selection bias.
3.Some participants in the study may have had posterior
epistaxis,where anterior packing may not be effective.
47. Weakness of the study
4.Dose of TXA used was 200mg,which was less than the 500
mg used in previous studies.
5. 25% of patients had their epistaxis managed with silver
nitrate cautery.
6.The ED management protocols for epistaxis in other
countries may differ.
