Efficacy of Tranexamic Acid in Upper Gastrointestinal Bleeding
Status:
Recruiting
Trial end date:
2021-06-30
Target enrollment:
Participant gender:
Summary
Upper Gastrointestinal bleed is a common presentation in a medical emergency. Patients
generally present with hematemesis, melena or in severe cases hematochezia. Incidence and
etiology vary from region as well as the level of health care facility. In the US, UGI bleed
accountsfor about 300000 admissions per year (6). India has a huge burden of UGI bleed. A
study in India showed 4.6% of hospitaladmissions were due to UGI bleed (7). As per the
medical record of PGIMER, 2-3 patients of UGIbleed are admitted to the EMOPD every day.
Upper GI bleed is anatomically defined as any gastrointestinal bleed originating proximal to
ligamentof treitz (8). Causes of UGI bleed are generally divided into variceal and
non-variceal in origin. The common etiology of non-variceal bleed are Peptic Ulcer disease
(PUD), esophagitis, erosive Gastritis, vascular malformations, Mallory Weiss tear and GI
malignancies.Variceal hemorrhage is usually secondary to esophageal varices, but alsocan be
due to gastric varices and ectopic varices of the upper GI tract(9).Non-varicealcauses are
more common as compared to variceal bleed (10) and among this PUD is the most common (10).But
there is recent rising trend of variceal bleed secondary to chronic liver disease and portal
hypertension .As per a recently published institutional study, variceal bleed constituted
45.7% of UGI bleed (11). Morbidity and mortality associated with UGI bleed are significantly
high.Variceal bleed is becoming a major concern in tertiarycare centers and carries a higher
mortality as compared to non variceal bleed(12 ).Clinical severity of UGI bleed may vary from
being insignificant to fatal. Mortality from UGI bleed may vary from 2 to 5% where as it
around 10-30% in cases of re-bleed (12). Prompt UGI endoscopic procedure is diagnostic as
well as therapeutic which should be done ideally within first 24hrsalong with airway, volume
and blood resuscitative measures (13).High dose proton pump inhibitors(PPI) are used for
non-variceal bleed where as splanchnic vasoconstrictorsare used in variceal bleed along with
endoscopic procedure like injection of Epinephrine, Sclerosants, application of haemostatic
material like hemoclips/endoclips, over the scope clips, glue or tissue adhesive, haemostatic
powder/spray. Beside these endoscopic bipolar electro coagulation, heater probe coagulation,
argon plasma coagulator, laser photocoagulation can also be done as and when required. For
variceal bleed endoscopic variceal band ligation (EVL) is the main stay of therapy. However
routine use of antifibrinolytic agent hasn't been recommended in the guidelines for
management of acute UGI bleed.
Studies have shown that fibrinolysis may play an important role in GI bleeding dueto
premature breakdown of fibrin blood clots at the bleeding site (14). Studies have also shown
that many patients with acute UGI bleed have elevated levels of fibrin degradation products
(a surrogate marker for fibrinolysis) and that is associated with worse outcomes (14).
Fibrinolysisalso contributes to the risk of re-bleed.Literature review suggests that early
administration ofTranexamic acid (TXA) reduces mortality due to bleeding in trauma patients
(15) and effective in controlling bleeding in menorrhagia (16). Our own institutional study
showed that TXA is effective as a bridging therapy in controlling bleeding from haemoptysis
before definitive therapeutic intervention done (1). A systematic COCHRANE review of TXA in
UGI bleed identified 7 trials (3). These trials showed statistically significant reduction in
mortality and reduced need ofsurgical interventions in patients receiving TXA. However the
trials had many fallacieslike small sample size, number of biases. The NICE guideline doesn't
include TXA inthe management of GI bleed (4). So far studies on use of TXA in UGI bleed
haven't been able to either recommend or refute the use of TXA in UGI bleed (3).
There is also lack of study form India and the Southeast Asia regarding the efficacy of TXA
in UGI bleed. TXA, an anti-fibrinolytic agent, inhibits fibrinolysis by displacing
plasminogen from fibrin. So, TXA may have role in bleeding control and preventing re-bleed in
acute UGI bleed by stabilization of the clot formation. This study will evaluate the efficacy
of early administration of TXA in acute onset UGIbleed, in term of bleeding control,
preventing re-bleeding and mortality.
Phase:
Phase 3
Details
Lead Sponsor:
Postgraduate Institute of Medical Education and Research