Gastro Intestinal BleedingPhase 3NCT04788121
Efficacy of Tranexamic Acid in Upper Gastrointestinal Bleeding
A Phase 3 study testing Tranexamic acid in people with Gastro Intestinal Bleeding, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastro Intestinal Bleeding
- What is being tested?
- Tranexamic acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 1 siteIndia
- Study dates
- 1 Nov 2020to 30 Jun 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Patients with UGI bleed for more than 48 hours, history of UGI bleed in previous 1 year
- Chronic kidney disease
- Pregnancy and breast feeding
- Malignancy
- Patients who have already received TXA
- UGI endoscopy done beyond 24 hours of admission because of hemodynamic instability or encephalopathy
- Patients who will be receiving blood thinners like anti-platelets, anti-coagulation agents within 4 weeks of presentation
Trial locations and contacts
1 site in 1 country.
Deba Prasad Dhibar, MD contact
India1 site, 1 recruiting
- Recruiting
Post Graduate Institute of Medical Education and Research
Chandigarh, 160012
Kushal Prasad Wasti, MD
About this study
Official title: Efficacy of Early Administration of Tranexamic Acid in Upper Gastrointestinal Bleeding: A Randomized Controlled Trial
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.
Read more
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
- Being tested
- Tranexamic acid, Standard of care
- Keywords
- GI bleed, Tranexamic Acid
- Medical subject headings
- Gastrointestinal Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tranexamic acidDrug
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 careOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment/Tranexamic Acid Group | Active comparator | 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. Receives: Drug: Tranexamic acid; Other: Standard of care |
| Control Group | Placebo comparator | The control group will receive injection 100 ml NS over 15 minutes infusion, followed by injection 500 ml NS over 12 hours infusion. Receives: Other: Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bleeding control
Bleeding control is defined as:
- No active hematemesis or no blood in the nasogastric (NG) aspirate (100 ml) > 2hrs after start of standard treatment.
- Absence of persistent shock or absence of installation of shock after initial contact (SBP<90/MAP<60/HR>100/min).
- No introduction or no increase of systemic vasopressors (except Terlipressin).
- Hemoglobin drop < 3gm/dl from the baseline within any 24 hour period if no transfusion is administered.
Measured: 24 hours
Re-bleed
Re-bleed is defined as:
- Hb drop of >2g/dl after 2 consecutive stable values > 3hours apart.
- Persistently dropping Hb>3g/dl in 24 hours associated with persistent hematemesis or malena.
- Development of new onset tachycardia (HR>110/min) or hypotension (SBP<90) after >1 hour of hemodynamic stability.
- New onset overt hematemesis.
- Presence of bright red blood in the stomach or duodenum or both at repeat endoscopy when more bleeding was suspected.
Measured: 72 hours
Secondary outcomes (5)
Mortality
incidence of death
Measured: 4 weeks
Change in D-dimer level
Change in D-dimer level before and after TXA therapy
Measured: 24 hours
ADR
Incidence of adverse drug reaction
Measured: 24 hours
Duration of hospital stay
Duration of hospital stay in numbers of days
Measured: 4 weeks
Need for blood transfusion
Number of Packed red blood cell (PRBC) need to be transfused
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2021
- Study start1 Nov 2020
- Primary completion30 Jun 2021 (estimated)
- Study completion30 Jun 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastro Intestinal BleedingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Deba Prasad Dhibar, Post Graduate Institute of Medical Education and Research, Chandigarh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04788121
- Sponsor's protocol ID
- PGI/IEC/2020/001466
- Status last verified
- Mar 2021
- First submitted
- 4 Mar 2021
- Last updated
- 9 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) is available with the principal investigator which may be considered for availability to others as per institutional ethic committee direction.
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Early Administration of Tranexamic Acid in Upper Gastrointestinal Bleeding: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04788121
- Acronym / sponsor ID
- PGI/IEC/2020/001466
- Conditions
- Gastro Intestinal Bleeding
- Keywords
- GI bleed, Tranexamic Acid
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Study start
- 1 Nov 2020 (actual)
- Primary completion
- 30 Jun 2021 (estimated)
- Study completion
- 30 Jun 2021 (estimated)
- First posted
- 9 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment/Tranexamic Acid Group | Active comparator | Drug: Tranexamic acid, Other: Standard of careThe 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. |
| Control Group | Placebo comparator | Other: Standard of careThe control group will receive injection 100 ml NS over 15 minutes infusion, followed by injection 500 ml NS over 12 hours infusion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (7 listed)
- Patients with UGI bleed for more than 48 hours, history of UGI bleed in previous 1 year
- Chronic kidney disease
- Pregnancy and breast feeding
- Malignancy
- Patients who have already received TXA
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tranexamic acidThe 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 | Drug | Treatment/Tranexamic Acid Group |
| Standard of careFor 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. | Other | Control Group, Treatment/Tranexamic Acid Group |
Primary outcome
Bleeding control
Time frame: 24 hours
Bleeding control is defined as: 1. No active hematemesis or no blood in the nasogastric (NG) aspirate (100 ml) > 2hrs after start of standard treatment. 2. Absence of persistent shock or absence of installation of shock after initial contact (SBP<90/MAP<60/HR>100/min). 3. No introduction or no increase of systemic vasopressors (except Terlipressin). 4. Hemoglobin drop < 3gm/dl from the baseline within any 24 hour period if no transfusion is administered.
Re-bleed
Time frame: 72 hours
Re-bleed is defined as: 1. Hb drop of >2g/dl after 2 consecutive stable values > 3hours apart. 2. Persistently dropping Hb>3g/dl in 24 hours associated with persistent hematemesis or malena. 3. Development of new onset tachycardia (HR>110/min) or hypotension (SBP<90) after >1 hour of hemodynamic stability. 4. New onset overt hematemesis. 5. Presence of bright red blood in the stomach or duodenum or both at repeat endoscopy when more bleeding was suspected.
5 secondary outcomes
Mortality
Time frame: 4 weeks
Change in D-dimer level
Time frame: 24 hours
ADR
Time frame: 24 hours
Duration of hospital stay
Time frame: 4 weeks
Need for blood transfusion
Time frame: 72 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2021.
- Individual participant dataSharing planned: No. Individual participant data (IPD) is available with the principal investigator which may be considered for availability to others as per institutional ethic committee direction.
Related trials for Gastro Intestinal Bleeding
RecruitingObservational study
Treatment Outcomes and Predictors After Endovascular Intervention for Portal Hypertension-Related Gastrointestinal Bleeding in Cirrhosis
Cirrhosis, Portal Hypertension Related to Cirrhosis
Active, not recruitingObservational study
Resumption of Anticoagulation After Major Gastrointestinal Bleeding in Patients With Atrial Fibrillation
Atrial Fibrillation (AF), Major Gastrointestinal Bleeding (MGIB)
RecruitingPhase 2
Fecal Microbiota Transplantation for Radiation-Induced Proctopathy
Radiation Induced Proctitis
Recruiting
OTSC vs. Angiographic Embolization in Patients With Refractory Non-variceal Upper Gastrointestinal Bleeding
Upper Gastrointestinal Bleeding
Not yet recruitingObservational study
Bleeding Reduction in Grade II-III Haemorrhoids Through Embolization Treatment
Hemorrhoid, Hemorrhoid Bleeding
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Deba Prasad Dhibar, MD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tranexamic acid in people with Gastro Intestinal Bleeding, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kushal Prasad Wasti, MD (6297958661, kopnepal@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bleeding control (time frame: 24 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2021.