Tranexamic Acid for Acute Upper Gastrointestinal Bleed in Cirrhosis
Primary Purpose
Liver Cirrhosis
Status
Recruiting
Phase
Not Applicable
Locations
India
Study Type
Interventional
Intervention
Tranexamic acid
Standard Medical Treatment
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Liver Cirrhosis
Eligibility Criteria
Inclusion Criteria:
- Patients greater than 18 years of age
- Presenting with Acute UGI bleed (< 24hrs from onset).
- Cirrhosis (Known Or suspected on clinical, biological, radiological data or the patient's history) with CTP B / C (i.e. CTP >/=7) or ACLF (with clinical evidence of cirrhosis).
Exclusion Criteria:
- Non cirrhotic patients
- Known allergy to Tranexamic Acid
- Patients with clinical evidence of DIC (Disseminated Intravascular Coagulation) like coagulopathy patches/ haematuria / uncontrolled epistaxis etc.
- Patients with Chronic Kidney Disease.
- History of recent Cerebro Vascular Accident (CVA) [in the past 6 months] or patients with thrombotic events [Portal Vein thrombosis /Hepatic vein thrombosis /other sites thrombosis]. HCC with tumour thrombosis will be included
- Any history of seizures, myocardial infarction
- Pregnancy/lactation
Sites / Locations
- Institute of Liver & Biliary SciencesRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Tranexamic Acid with Standard Medical Treatment
Placebo + Standard Medical treatment
Arm Description
Arm A will 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.
Outcomes
Primary Outcome Measures
Proportion of patients developing five-day treatment failure in both the groups
Secondary Outcome Measures
Number of patients with failure to prevent rebleed in both group
Clinically significant rebleed in both groups
Clinically significant rebleed as monitored by hemoglobin drop by 3g/dl, need of blood transfusion
Number of patients who will require salvage therapy in both groups
Number of patients who will require Blood product and component in both groups
Number of days in Intensive Care Unit in both groups
Number of days in hospital in both groups
Number of patients with deep vein thrombosis in both groups
Number of patients with pulmonary embolism in both groups
Number of patients with stroke in both groups
Number of patients with myocardial infarction in both groups
Number of patients with Adverse Events associated with post bleed in both groups
Number of patients with Mortality attributed to failure to control bleed in both groups
Full Information
NCT ID
NCT04489108
First Posted
July 20, 2020
Last Updated
January 27, 2022
Sponsor
Institute of Liver and Biliary Sciences, India
1. Study Identification
Unique Protocol Identification Number
NCT04489108
Brief Title
Tranexamic Acid for Acute Upper Gastrointestinal Bleed in Cirrhosis
Official Title
Tranexamic Acid for Acute Upper Gastrointestinal Bleed in Cirrhosis - A Randomized Placebo Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 5, 2020 (Actual)
Primary Completion Date
April 30, 2022 (Anticipated)
Study Completion Date
April 30, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institute of Liver and Biliary Sciences, India
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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 (i.e., failure to control bleed) in patients with cirrhosis presenting with Upper GI bleed
Primary Objective:
Proportion of patients developing five-day treatment failure (i.e., failure to control bleed)
Secondary Objectives:
Failure to prevent rebleed within 6 weeks
Clinically significant rebleed within 6 weeks (monitored by hemoglobin drop by 3g/dl, need of blood transfusion)
Need for salvage therapy (tamponade, additional endoscopic therapy, TIPS, surgery etc.)
Blood product and component requirements
Days of ICU/hospital stay
Thromboembolic events (deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction etc)
Other complications post bleed (including other significant cardiac event, sepsis, pneumonia, respiratory failure, Acute Kidney Injury, seizures etc)
Mortality attributed to failure to control bleed.
Methodology:
Study population: Patients of Cirrhosis presenting with Acute Upper Gastrointestinal bleed
Study design:Single Centre, Double Blinded (Patient and Treating physician), Placebo Controlled (Saline), Randomised Controlled Trial
Study period: 1.5 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:
Five-day treatment failure (i.e., 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.
Failure to prevent rebleeding defined as a single episode of clinically significant rebleeding after day 5 until 6 weeks, and
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
Conditioning (intravenous access, tracheal intubation or other airways management technique if needed)
Medical interventions (immediate splanchnic vasopressors: terlipressin or somatostatin and derivatives before endoscopy (up to 5 days)
PPIs in case of suspicion of associated peptic ulcer
Antibiotics during 5 days and later as needed
Hemodynamic stabilisation (fluid infusion, systemic vasopressors as noradrenalin or adrenalin);
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)
Secondary prophylaxis (from day 6 after onset): beta blockers if stable will be mandatory for the secondary prophylaxis.
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 > 1.8 and/or PLTs < 50 × 109/L.
Assessment of Fibrinolysis:
FDP (Fibrin Degradation Products)
d-Dimer assay
Fibrinogen
FIBTEM-EXTEM
Data to be Collected
Hemogram, PT/INR, LFT, KFT (baseline, D1, 3, 5, 7, 14, 28, 42 and as needed)
d-Dimer, FDP, Fibrinogen, ROTEM (FIBTEM/EXTEM): (baseline, day 1, 3, 5)
USG with doppler SPA, AFP, sugar (F),Chest Xray other etiological investigations as needed: baseline
UGIE findings
Other clinical parameters such as CTP score, MELD score, Heart rate, Blood Pressure
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cirrhosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
600 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Tranexamic Acid with Standard Medical Treatment
Arm Type
Experimental
Arm Description
Arm A will 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 Title
Placebo + Standard Medical treatment
Arm Type
Active Comparator
Arm Description
Arm B will receive similar volume of isotonic solution (saline) along with standard medical and interventional (Endoscopy) therapy.
Intervention Type
Drug
Intervention Name(s)
Tranexamic acid
Intervention Description
Tranexamic Acid 1g iv bolus as loading dose followed by 3g Tranexamic Acid infused over next 24 hours
Intervention Type
Other
Intervention Name(s)
Standard Medical Treatment
Intervention Description
Standard Medical Treatment
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
isotonic solution (saline)
Primary Outcome Measure Information:
Title
Proportion of patients developing five-day treatment failure in both the groups
Time Frame
5 day
Secondary Outcome Measure Information:
Title
Number of patients with failure to prevent rebleed in both group
Time Frame
6 weeks
Title
Clinically significant rebleed in both groups
Description
Clinically significant rebleed as monitored by hemoglobin drop by 3g/dl, need of blood transfusion
Time Frame
6 weeks
Title
Number of patients who will require salvage therapy in both groups
Time Frame
6 weeks
Title
Number of patients who will require Blood product and component in both groups
Time Frame
6 weeks
Title
Number of days in Intensive Care Unit in both groups
Time Frame
6 weeks
Title
Number of days in hospital in both groups
Time Frame
6 weeks
Title
Number of patients with deep vein thrombosis in both groups
Time Frame
6 weeks
Title
Number of patients with pulmonary embolism in both groups
Time Frame
6 weeks
Title
Number of patients with stroke in both groups
Time Frame
6 weeks
Title
Number of patients with myocardial infarction in both groups
Time Frame
6 weeks
Title
Number of patients with Adverse Events associated with post bleed in both groups
Time Frame
6 weeks
Title
Number of patients with Mortality attributed to failure to control bleed in both groups
Time Frame
6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients greater than 18 years of age
Presenting with Acute UGI bleed (< 24hrs from onset).
Cirrhosis (Known Or suspected on clinical, biological, radiological data or the patient's history) with CTP B / C (i.e. CTP >/=7) or ACLF (with clinical evidence of cirrhosis).
Exclusion Criteria:
Non cirrhotic patients
Known allergy to Tranexamic Acid
Patients with clinical evidence of DIC (Disseminated Intravascular Coagulation) like coagulopathy patches/ haematuria / uncontrolled epistaxis etc.
Patients with Chronic Kidney Disease.
History of recent Cerebro Vascular Accident (CVA) [in the past 6 months] or patients with thrombotic events [Portal Vein thrombosis /Hepatic vein thrombosis /other sites thrombosis]. HCC with tumour thrombosis will be included
Any history of seizures, myocardial infarction
Pregnancy/lactation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dr Shantan Venishetty, MD
Phone
01146300000
Email
venishantan@gmail.com
Facility Information:
Facility Name
Institute of Liver & Biliary Sciences
City
New Delhi
State/Province
Delhi
ZIP/Postal Code
110070
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr Shantan Venishetty, MD
Phone
01146300000
Email
venishantan@gmail.com
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Tranexamic Acid for Acute Upper Gastrointestinal Bleed in Cirrhosis
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