Ignite Creation Date:
2024-05-06 @ 2:59 PM
Last Modification Date:
2024-10-26 @ 1:41 PM
Study NCT ID:
NCT04489108
Status:
UNKNOWN
Last Update Posted:
2022-01-31
First Post:
2020-07-20
Brief Title:
Tranexamic Acid for Acute Upper Gastrointestinal Bleed in Cirrhosis
Sponsor:
Institute of Liver and Biliary Sciences India
Organization:
Institute of Liver and Biliary Sciences India
Study Overview
Official Title:
Tranexamic Acid for Acute Upper Gastrointestinal Bleed in Cirrhosis - A Randomized Placebo Controlled Trial
Status:
UNKNOWN
Status Verified Date:
2022-01
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The management of acute upper gastrointestinal bleeding UGIB is challenging in patients with cirrhosis as it is responsible for severe complications and high mortality rates Fibrinolytic activity of the epithelial surfaces and of the submucosal blood vessels may interfere with hematemesis and even delay healing of ulcers Tranexamic acid TXA may help control the bleeding by counterbalancing cirrhosis-related hyperfibrinolysis Still there is a lack of unbiased data to conclude on its efficacy Tranexamic Acid in patients with acute Upper Gastrointestinal bleed have been shown to prevent re bleed in few studies when combined with standard medical management which generally comprises of initial fluid resuscitation intravenous PPI splanchnic vasoconstrictors blood transfusions and coagulopathy corrections as per lab parameters but no randomized placebo controlled trial has been done The aim of this study is to evaluate the efficacy of TXA in the early treatment of acute UGIB as compared to placebo in patients with cirrhosis
Detailed Description:
Aim and Objective - AIM- To compare the efficacy and safety of tranexamic acid in reducing 5-day treatment failure ie failure to control bleed in patients with cirrhosis presenting with Upper GI bleed
Primary Objective
Proportion of patients developing five-day treatment failure ie failure to control bleed
Secondary Objectives
1 Failure to prevent rebleed within 6 weeks
2 Clinically significant rebleed within 6 weeks monitored by hemoglobin drop by 3gdl need of blood transfusion
3 Need for salvage therapy tamponade additional endoscopic therapy TIPS surgery etc
4 Blood product and component requirements
5 Days of ICUhospital stay
6 Thromboembolic events deep vein thrombosis pulmonary embolism stroke myocardial infarction etc
7 Other complications post bleed including other significant cardiac event sepsis pneumonia respiratory failure Acute Kidney Injury seizures etc
8 Mortality attributed to failure to control bleed
Methodology
Study population Patients of Cirrhosis presenting with Acute Upper Gastrointestinal bleed
Study designSingle Centre Double Blinded Patient and Treating physician Placebo Controlled Saline Randomised Controlled Trial
Study period 15 years from the date of ethics approval
Sample size with justification
- Assuming 5-day treatment failure in Placebo arm around 25 and 15 in the treatment arm Alpha- 5 Power- 80 The investigators need to enroll 542 cases with 271 in each group Further assuming 10 dropout it is decided to enroll 600 cases randomly allocated into two arms by Block Randomization with Block size of 10 An interim analysis will be done at reaching total of 300 sample size
Intervention
- Patients will be randomized into two Arms A B Both the patient and treating physician are blinded Arm A- Tranexamic Acid arm- Will receive Tranexamic Acid 1g iv bolus as loading dose followed by 3g Tranexamic Acid infused over next 24 hours along with standard medical and interventional Endoscopy therapy
Arm B- Will receive similar volume of isotonic solution saline along with standard medical and interventional Endoscopy therapy
Monitoring and Assessment
1 Five-day treatment failure ie failure to control bleed- defined as death or need to change therapy defined by one of the following criteria
fresh hematemesis or
nasogastric aspiration of 100 mL of fresh blood 2 hours after the start of a specific drug treatment or
therapeutic endoscopy
development of hypovolaemic shock
3 g drop in hemoglobin Hb 9 drop of hematocrit within any 24-hour period if no transfusion is administered
2 Failure to prevent rebleeding defined as a single episode of clinically significant rebleeding after day 5 until 6 weeks and
3 Clinically significant rebleeding defined as recurrent melena or hematemesis resulting in any of the following after day 5 until 6 weeks
hospital admission
blood transfusion
3 g drop in haemoglobin or
Death
Other treatments given
1 Conditioning intravenous access tracheal intubation or other airways management technique if needed
2 Medical interventions immediate splanchnic vasopressors terlipressin or somatostatin and derivatives before endoscopy up to 5 days
3 PPIs in case of suspicion of associated peptic ulcer
4 Antibiotics during 5 days and later as needed
5 Hemodynamic stabilisation fluid infusion systemic vasopressors as noradrenalin or adrenalin
6 Technical interventions endoscopy as soon as possible within 12 hours and haemostatic interventions like EVL Glue Dannis-Ella stent if feasible early TIPS within 72 hours Child C or B with active bleeding at endoscopy
7 Secondary prophylaxis from day 6 after onset beta blockers if stable will be mandatory for the secondary prophylaxis
8 ROTEM based correction will be given for patients having nonvariceal upper GI bleeding diagnosed after doing upper GI endoscopy and showing ongoing bleed form a nonvariceal source at that time and significant coagulopathy assessed by INR 18 andor PLTs 50 109L
Assessment of Fibrinolysis
1 FDP Fibrin Degradation Products
2 d-Dimer assay
3 Fibrinogen
4 FIBTEM-EXTEM
Data to be Collected
1 Hemogram PTINR LFT KFT baseline D1 3 5 7 14 28 42 and as needed
2 d-Dimer FDP Fibrinogen ROTEM FIBTEMEXTEM baseline day 1 3 5
3 USG with doppler SPA AFP sugar FChest Xray other etiological investigations as needed baseline
4 UGIE findings
5 Other clinical parameters such as CTP score MELD score Heart rate Blood Pressure
Primary Objective
Proportion of patients developing five-day treatment failure ie failure to control bleed
Secondary Objectives
1 Failure to prevent rebleed within 6 weeks
2 Clinically significant rebleed within 6 weeks monitored by hemoglobin drop by 3gdl need of blood transfusion
3 Need for salvage therapy tamponade additional endoscopic therapy TIPS surgery etc
4 Blood product and component requirements
5 Days of ICUhospital stay
6 Thromboembolic events deep vein thrombosis pulmonary embolism stroke myocardial infarction etc
7 Other complications post bleed including other significant cardiac event sepsis pneumonia respiratory failure Acute Kidney Injury seizures etc
8 Mortality attributed to failure to control bleed
Methodology
Study population Patients of Cirrhosis presenting with Acute Upper Gastrointestinal bleed
Study designSingle Centre Double Blinded Patient and Treating physician Placebo Controlled Saline Randomised Controlled Trial
Study period 15 years from the date of ethics approval
Sample size with justification
- Assuming 5-day treatment failure in Placebo arm around 25 and 15 in the treatment arm Alpha- 5 Power- 80 The investigators need to enroll 542 cases with 271 in each group Further assuming 10 dropout it is decided to enroll 600 cases randomly allocated into two arms by Block Randomization with Block size of 10 An interim analysis will be done at reaching total of 300 sample size
Intervention
- Patients will be randomized into two Arms A B Both the patient and treating physician are blinded Arm A- Tranexamic Acid arm- Will receive Tranexamic Acid 1g iv bolus as loading dose followed by 3g Tranexamic Acid infused over next 24 hours along with standard medical and interventional Endoscopy therapy
Arm B- Will receive similar volume of isotonic solution saline along with standard medical and interventional Endoscopy therapy
Monitoring and Assessment
1 Five-day treatment failure ie failure to control bleed- defined as death or need to change therapy defined by one of the following criteria
fresh hematemesis or
nasogastric aspiration of 100 mL of fresh blood 2 hours after the start of a specific drug treatment or
therapeutic endoscopy
development of hypovolaemic shock
3 g drop in hemoglobin Hb 9 drop of hematocrit within any 24-hour period if no transfusion is administered
2 Failure to prevent rebleeding defined as a single episode of clinically significant rebleeding after day 5 until 6 weeks and
3 Clinically significant rebleeding defined as recurrent melena or hematemesis resulting in any of the following after day 5 until 6 weeks
hospital admission
blood transfusion
3 g drop in haemoglobin or
Death
Other treatments given
1 Conditioning intravenous access tracheal intubation or other airways management technique if needed
2 Medical interventions immediate splanchnic vasopressors terlipressin or somatostatin and derivatives before endoscopy up to 5 days
3 PPIs in case of suspicion of associated peptic ulcer
4 Antibiotics during 5 days and later as needed
5 Hemodynamic stabilisation fluid infusion systemic vasopressors as noradrenalin or adrenalin
6 Technical interventions endoscopy as soon as possible within 12 hours and haemostatic interventions like EVL Glue Dannis-Ella stent if feasible early TIPS within 72 hours Child C or B with active bleeding at endoscopy
7 Secondary prophylaxis from day 6 after onset beta blockers if stable will be mandatory for the secondary prophylaxis
8 ROTEM based correction will be given for patients having nonvariceal upper GI bleeding diagnosed after doing upper GI endoscopy and showing ongoing bleed form a nonvariceal source at that time and significant coagulopathy assessed by INR 18 andor PLTs 50 109L
Assessment of Fibrinolysis
1 FDP Fibrin Degradation Products
2 d-Dimer assay
3 Fibrinogen
4 FIBTEM-EXTEM
Data to be Collected
1 Hemogram PTINR LFT KFT baseline D1 3 5 7 14 28 42 and as needed
2 d-Dimer FDP Fibrinogen ROTEM FIBTEMEXTEM baseline day 1 3 5
3 USG with doppler SPA AFP sugar FChest Xray other etiological investigations as needed baseline
4 UGIE findings
5 Other clinical parameters such as CTP score MELD score Heart rate Blood Pressure
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None