Efficacy of Tranexamic Acid in Upper Gastrointestinal Bleeding

NCT ID: NCT04788121

Last Updated: 2021-03-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-01
• Study Completion Date: 2021-06-30

Brief 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.

Conditions

Gastro Intestinal Bleeding

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Treatment/Tranexamic Acid Group

The treatment group will receive Injection TXA 1gm intravenous (IV) over 15 minutes infusion dissolved in 100 ml normal saline (NS- 0.9% NaCl), followed by injection TXA 2 g IV over 12 hours infusion dissolved in a 500 ml NS.

Group Type: ACTIVE_COMPARATOR

Tranexamic acid

Intervention Type: DRUG

The treatment group will receive Injection TXA 1gm intravenous (IV) over 15 minutes infusion dissolved in 100 ml normal saline (NS- 0.9% NaCl), followed by injection TXA 2 g IV over 12 hours infusion dissolved in a 500 ml NS

Standard of care

Intervention Type: OTHER

For management, initial priority will be given to secure airway, breathing and circulation. To ensure hemodynamic stability, crystalloids infusion will be given as and when required. Blood transfusion will be initiated at the threshold hemoglobin (Hb) of 7g/dl, to maintain the target Hb of 7-9g/dl or with signs of hemodynamic instability despite fluid resuscitation. Intra venous (IV) PPI and antibiotic will be started promptly in all cases and IV splanchnic vasoconstrictor will be given in all suspicious case of Variceal hemorrhage before definitive therapeutic and diagnostic endoscopic procedure is done.

Control Group

The control group will receive injection 100 ml NS over 15 minutes infusion, followed by injection 500 ml NS over 12 hours infusion.

Group Type: PLACEBO_COMPARATOR

Standard of care

Intervention Type: OTHER

For management, initial priority will be given to secure airway, breathing and circulation. To ensure hemodynamic stability, crystalloids infusion will be given as and when required. Blood transfusion will be initiated at the threshold hemoglobin (Hb) of 7g/dl, to maintain the target Hb of 7-9g/dl or with signs of hemodynamic instability despite fluid resuscitation. Intra venous (IV) PPI and antibiotic will be started promptly in all cases and IV splanchnic vasoconstrictor will be given in all suspicious case of Variceal hemorrhage before definitive therapeutic and diagnostic endoscopic procedure is done.

Interventions

Tranexamic acid

The treatment group will receive Injection TXA 1gm intravenous (IV) over 15 minutes infusion dissolved in 100 ml normal saline (NS- 0.9% NaCl), followed by injection TXA 2 g IV over 12 hours infusion dissolved in a 500 ml NS

Intervention Type: DRUG

Standard of care

For management, initial priority will be given to secure airway, breathing and circulation. To ensure hemodynamic stability, crystalloids infusion will be given as and when required. Blood transfusion will be initiated at the threshold hemoglobin (Hb) of 7g/dl, to maintain the target Hb of 7-9g/dl or with signs of hemodynamic instability despite fluid resuscitation. Intra venous (IV) PPI and antibiotic will be started promptly in all cases and IV splanchnic vasoconstrictor will be given in all suspicious case of Variceal hemorrhage before definitive therapeutic and diagnostic endoscopic procedure is done.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Irrespective of gender and with age ≥ 18 years, all the patients presenting with symptoms of acute UGI bleed will be enrolled for the study after taking written informed consent.

Exclusion Criteria

1. Patients with UGI bleed for more than 48 hours, history of UGI bleed in previous 1 year

2. Chronic kidney disease

3. Pregnancy and breast feeding

4. Malignancy

5. Patients who have already received TXA

6. UGI endoscopy done beyond 24 hours of admission because of hemodynamic instability or encephalopathy

7. Patients who will be receiving blood thinners like anti-platelets, anti-coagulation agents within 4 weeks of presentation

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Post Graduate Institute of Medical Education and Research, Chandigarh

OTHER

Sponsor Role: lead

Responsible Party

Deba Prasad Dhibar

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Post Graduate Institute of Medical Education and Research

Chandigarh, , India

Site Status: RECRUITING

Countries

India

Central Contacts

Kushal Prasad Wasti, MD

Role: CONTACT

kopnepal@gmail.com

6297958661

Deba Prasad Dhibar, MD

Role: CONTACT

dhibar.dp@pgimer.edu.in

Facility Contacts

Kushal Prasad Wasti, MD

Role: primary

Other Identifiers

PGI/IEC/2020/001466

Identifier Type: -

Identifier Source: org_study_id