Effectiveness of Intravenous Tranexamic Acid in Primary Cerebral Hemorrhage for Prevention of Hematoma Progression: Protocol for a Randomized, Double Blind Placebo-controlled Trial

• ClinicalTrials.gov Identifier: NCT04742205
• Recruitment Status: Not yet recruiting
• First Posted: February 8, 2021
• Last Update Posted: February 8, 2021
• Sponsor: Kathmandu Medical College and Teaching Hospital
• Information provided by (Responsible Party): Bibesh Pokhrel, Kathmandu Medical College and Teaching Hospital

Study Description

Brief Summary:

Intracerebral hemorrhage is increasingly becoming a major burden in the society because of significant morbidity as well as mortality. Hematoma volume at the time of presentation as well as hematoma expansion and re-bleed or ongoing bleed further deteriorates the patient making a poor prognosis, however at present no therapy targets this pathological process. Though clinical studies do report benefit of using tranexamic acid in spontaneous intracerebral hemorrhage by reducing hematoma expansion rate as well as decreasing ongoing bleed, large randomized controlled trials have not shown any convincing advantage owing to various limitations in their design and methods. However, they uniformly did not find any significant side effect with the use of tranexamic acid.

The aim of this study is to test the hypothesis that intravenous tranexamic acid is superior to placebo by reducing hematoma expansion when given within 24 h of spontaneous intracerebral hemorrhage.

Condition or disease	Intervention/treatment	Phase
Effectiveness of Intravenous Tranexamic Acid in Primary Cerebral Hemorrhage	Drug: Tranexamic Acid 500 MG	Early Phase 1

Detailed Description:

Patients and Methods: Data will be collected (after Nepal Health Research Council approval) for 1 year as patient gets admitted with Intracerebral haemorrhage. 160 spontaneous intracerebral haemorrhage patients presenting within 24 hours of ictus or last known well will be taken in the study. Outcomes of these patients will be calculated to establish a relationship between hematoma expansion, underlying pathology and outcome of the patients.

Results: Primary outcome i.e. radiological improvement (CT scan): Difference between hematoma volume with perilesional edema from baseline and 48-hour post treatment scan, hematoma location, and new infarction.

Secondary outcomes: Neurological impairment (National Institutes of Health Stroke Scale) at day 7, Outcome: Dependency (modified Ranking Scale), Cognition (Telephone Interview Cognition Score-Modified), and mood (Zung Depression Scale) at days 10 and 90 and 180. Similarly, costs: Length of stay in hospital, readmission, ability to return back to daily activities. Also, Safety endpoints recorded until day 90: Death (cause), venous thromboembolism confirmed by ultrasound, vascular occlusive events (stroke/transient ischemic attack/myocardial infarction/peripheral artery disease), seizures. Serious adverse events (AEs) in first seven days will be analyzed and calculated.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 142 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Effectiveness of Intravenous Tranexamic Acid in Primary Cerebral Hemorrhage for Prevention of Hematoma Progression: Protocol for a Randomized, Double Blind Placebo-controlled Trial
• Estimated Study Start Date: February 2021
• Estimated Primary Completion Date: January 2022
• Estimated Study Completion Date: July 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: tranexamic acid; Four 5ml solution of either tranexamic acid 500mg or sodium chloride 0.9% are distributed which cannot be differentiated from the appearance. Loading dose of trial (1g of tranexamic acid in 10ml) or placebo (10 ml of sodium chloride 0.9%) is mixed in 100ml sodium chloride 0.9% and given over 10 minutes. Maintenance dose of trial or placebo mixed in 500ml sodium chloride 0.9% is given over 8 hours	Drug: Tranexamic Acid 500 MG; Loading dose of trial (1g of tranexamic acid in 10ml) is mixed in 100ml sodium chloride 0.9% and given over 10 minutes. Maintenance dose of trial mixed in 500ml sodium chloride 0.9% is given over 8 hours
Placebo Comparator: Sodium Chloride; Four 5ml solution of either tranexamic acid 500mg or sodium chloride 0.9% are distributed which cannot be differentiated from the appearance. Loading dose of trial (1g of tranexamic acid in 10ml) or placebo (10 ml of sodium chloride 0.9%) is mixed in 100ml sodium chloride 0.9% and given over 10 minutes. Maintenance dose of trial or placebo mixed in 500ml sodium chloride 0.9% is given over 8 hours	Drug: Tranexamic Acid 500 MG; Loading dose of trial (1g of tranexamic acid in 10ml) is mixed in 100ml sodium chloride 0.9% and given over 10 minutes. Maintenance dose of trial mixed in 500ml sodium chloride 0.9% is given over 8 hours

Outcome Measures

Primary Outcome Measures :

1. Radiological improvement (CT scan) [ Time Frame: 48 hour ]
   Difference between hematoma volume with perilesional edema from baseline and 48-hour post treatment scan, hematoma location, and new infarction.

Secondary Outcome Measures :

1. National Institutes of Health Stroke Scale [ Time Frame: day 7 ]
   Neurological impairment (score:0-42; 0:favourable outcome)
2. Barthel index [ Time Frame: days 10 and 90, 180 ]
   Disability (score:0-100; 100: independent)
3. modified rankin scale [ Time Frame: days 10 and 90, 180 ]
   dependency (score:0-5; 0: no symptom)
4. Modified Telephone Interview for Cognitive Status (TICS-M) [ Time Frame: days 10 and 90, 180 ]
   Cognition done by Telephone Interview
5. Zung Depression Scale [ Time Frame: days 10 and 90, 180 ]
   mood (score:0-80; lessscore: no depression)

Other Outcome Measures:

1. Death (cause) [ Time Frame: day 180 ]
   Cause of death

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. All patients presenting to the emergency department with symptom of hemorrhagic stroke within 24 hours from onset of symptom or last seen well.
2. Patient who had a follow up

Exclusion Criteria:

1. Glasgow coma scale <9 after resuscitation (as this can lead to biasness; requires surgery)
2. Contraindication to tranexamic acid,
3. Hemorrhagic stroke secondary to trauma,
4. Hemorrhage was caused by coagulopathy

Contacts and Locations

Contacts

Contact: Bibesh Pokhrel, MS; +9779849671672; bibeshpokharel@yahoo.com

Sponsors and Collaborators

Kathmandu Medical College and Teaching Hospital

Investigators

• Study Chair: Deepak Regmi, MS; KMC AmbA

More Information

• Responsible Party: Bibesh Pokhrel, Registrar, Kathmandu Medical College and Teaching Hospital
• ClinicalTrials.gov Identifier: NCT04742205
• Other Study ID Numbers: KathmanduMCTH
• First Posted: February 8, 2021
• Last Update Posted: February 8, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Bibesh Pokhrel, Kathmandu Medical College and Teaching Hospital:

double blind randomized trial; spontaneous intracerebral hemorrhage; tranexamic acid

Additional relevant MeSH terms:

Cerebral Hemorrhage; Hemorrhage; Hematoma; Pathologic Processes; Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Tranexamic Acid; Antifibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Hemostatics; Coagulants