ITCH Trial: Protocol for a Randomized, Double Blind Placebo-controlled Trial

NCT04742205 | Completed Phase 2 DMC

• 1 other identifier: KathmanduMCTH
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 1

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.

Conditions

Cerebral Hemorrhage

Keywords

double blind randomized trial; spontaneous intracerebral hemorrhage; tranexamic acid

Outcome Measures

Primary Outcomes (1)

• Radiological improvement (CT scan)

  Difference between hematoma volume from baseline and 48-hour post treatment scan

  48 hour

Secondary Outcomes (3)

• National Institutes of Health Stroke Scale

  day 10

• Barthel index

  days 10

• modified rankin scale

  days 10 and 30, 90, 180

Other Outcomes (1)

• Death

  day 180

Study Arms (2)

tranexamic acid

ACTIVE COMPARATOR

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

Sodium Chloride

PLACEBO COMPARATOR

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

Interventions

Tranexamic Acid 500 MG DRUG

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

Sodium Chloride; tranexamic acid

Eligibility Criteria

• Age: 20 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Glasgow coma scale \<8 after resuscitation (as this can lead to biasness; requires surgery)
• Contraindication to tranexamic acid,
• Hemorrhagic stroke secondary to trauma,
• Hemorrhage was caused by coagulopathy

Sponsors & Collaborators

• Kathmandu Medical College and Teaching Hospital: lead

Study Sites (1)

KMC Teaching Hospital, Kathmandu, Nepal

Kathmandu, Bagmati, 44811, Nepal

Location

Related Publications (17)

• Qureshi AI, Palesch YY, Barsan WG, Hanley DF, Hsu CY, Martin RL, Moy CS, Silbergleit R, Steiner T, Suarez JI, Toyoda K, Wang Y, Yamamoto H, Yoon BW; ATACH-2 Trial Investigators and the Neurological Emergency Treatment Trials Network. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. N Engl J Med. 2016 Sep 15;375(11):1033-43. doi: 10.1056/NEJMoa1603460. Epub 2016 Jun 8.

  PMID: 27276234 BACKGROUND

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  PMID: 20056489 BACKGROUND

• Dowlatshahi D, Demchuk AM, Flaherty ML, Ali M, Lyden PL, Smith EE; VISTA Collaboration. Defining hematoma expansion in intracerebral hemorrhage: relationship with patient outcomes. Neurology. 2011 Apr 5;76(14):1238-44. doi: 10.1212/WNL.0b013e3182143317. Epub 2011 Feb 23.

  PMID: 21346218 BACKGROUND

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  PMID: 23466430 BACKGROUND

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  PMID: 20044536 BACKGROUND

• Flaherty ML, Haverbusch M, Sekar P, Kissela B, Kleindorfer D, Moomaw CJ, Sauerbeck L, Schneider A, Broderick JP, Woo D. Long-term mortality after intracerebral hemorrhage. Neurology. 2006 Apr 25;66(8):1182-6. doi: 10.1212/01.wnl.0000208400.08722.7c.

  PMID: 16636234 BACKGROUND

• Zehtabchi S, Abdel Baki SG, Falzon L, Nishijima DK. Tranexamic acid for traumatic brain injury: a systematic review and meta-analysis. Am J Emerg Med. 2014 Dec;32(12):1503-9. doi: 10.1016/j.ajem.2014.09.023. Epub 2014 Sep 28.

  PMID: 25447601 BACKGROUND

• Roos Y, Rinkel G, Vermeulen M, Algra A, van Gijn J. Antifibrinolytic therapy for aneurysmal subarachnoid hemorrhage: a major update of a cochrane review. Stroke. 2003 Sep;34(9):2308-9. doi: 10.1161/01.STR.0000089030.04120.0E. Epub 2003 Aug 21. No abstract available.

  PMID: 12933970 BACKGROUND

• Germans MR, Post R, Coert BA, Rinkel GJ, Vandertop WP, Verbaan D. Ultra-early tranexamic acid after subarachnoid hemorrhage (ULTRA): study protocol for a randomized controlled trial. Trials. 2013 May 16;14:143. doi: 10.1186/1745-6215-14-143.

  PMID: 23680226 BACKGROUND

• Mahmood A, Roberts I, Shakur H. A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial (CRASH-3 Trial Intracranial Bleeding Mechanistic Sub-Study [CRASH-3 IBMS]). Trials. 2017 Jul 17;18(1):330. doi: 10.1186/s13063-017-2073-6.

  PMID: 28716153 BACKGROUND

• Anderson CS, Huang Y, Wang JG, Arima H, Neal B, Peng B, Heeley E, Skulina C, Parsons MW, Kim JS, Tao QL, Li YC, Jiang JD, Tai LW, Zhang JL, Xu E, Cheng Y, Heritier S, Morgenstern LB, Chalmers J; INTERACT Investigators. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurol. 2008 May;7(5):391-9. doi: 10.1016/S1474-4422(08)70069-3. Epub 2008 Apr 7.

  PMID: 18396107 BACKGROUND

• Arumugam A, A Rahman NA, Theophilus SC, Shariffudin A, Abdullah JM. Tranexamic Acid as Antifibrinolytic Agent in Non Traumatic Intracerebral Hemorrhages. Malays J Med Sci. 2015 Dec;22(Spec Issue):62-71.

  PMID: 27006639 BACKGROUND

• Sprigg N, Flaherty K, Appleton JP, Al-Shahi Salman R, Bereczki D, Beridze M, Christensen H, Ciccone A, Collins R, Czlonkowska A, Dineen RA, Duley L, Egea-Guerrero JJ, England TJ, Krishnan K, Laska AC, Law ZK, Ozturk S, Pocock SJ, Roberts I, Robinson TG, Roffe C, Seiffge D, Scutt P, Thanabalan J, Werring D, Whynes D, Bath PM; TICH-2 Investigators. Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial. Lancet. 2018 May 26;391(10135):2107-2115. doi: 10.1016/S0140-6736(18)31033-X. Epub 2018 May 16.

  PMID: 29778325 BACKGROUND

• Gayet-Ageron A, Prieto-Merino D, Ker K, Shakur H, Ageron FX, Roberts I; Antifibrinolytic Trials Collaboration. Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: a meta-analysis of individual patient-level data from 40 138 bleeding patients. Lancet. 2018 Jan 13;391(10116):125-132. doi: 10.1016/S0140-6736(17)32455-8. Epub 2017 Nov 7.

  PMID: 29126600 BACKGROUND

• O'Donnell MJ, Chin SL, Rangarajan S, Xavier D, Liu L, Zhang H, Rao-Melacini P, Zhang X, Pais P, Agapay S, Lopez-Jaramillo P, Damasceno A, Langhorne P, McQueen MJ, Rosengren A, Dehghan M, Hankey GJ, Dans AL, Elsayed A, Avezum A, Mondo C, Diener HC, Ryglewicz D, Czlonkowska A, Pogosova N, Weimar C, Iqbal R, Diaz R, Yusoff K, Yusufali A, Oguz A, Wang X, Penaherrera E, Lanas F, Ogah OS, Ogunniyi A, Iversen HK, Malaga G, Rumboldt Z, Oveisgharan S, Al Hussain F, Magazi D, Nilanont Y, Ferguson J, Pare G, Yusuf S; INTERSTROKE investigators. Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study. Lancet. 2016 Aug 20;388(10046):761-75. doi: 10.1016/S0140-6736(16)30506-2. Epub 2016 Jul 16.

  PMID: 27431356 BACKGROUND

• Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) investigators. Antihypertensive treatment of acute cerebral hemorrhage. Crit Care Med. 2010 Feb;38(2):637-48. doi: 10.1097/CCM.0b013e3181b9e1a5.

  PMID: 19770736 BACKGROUND

• Eilertsen H, Menon CS, Law ZK, Chen C, Bath PM, Steiner T, Desborough MJ, Sandset EC, Sprigg N, Al-Shahi Salman R. Haemostatic therapies for stroke due to acute, spontaneous intracerebral haemorrhage. Cochrane Database Syst Rev. 2023 Oct 23;10(10):CD005951. doi: 10.1002/14651858.CD005951.pub5.

  PMID: 37870112 DERIVED

MeSH Terms

Conditions

Cerebral Hemorrhage

Interventions

Tranexamic Acid

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Deepak Regmi, MS

  KMC AmbA

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer

Study Record Dates

• First Submitted: January 28, 2021
• First Posted: February 8, 2021
• Study Start: February 8, 2021
• Primary Completion: December 5, 2023
• Study Completion: June 4, 2024
• Last Updated: March 19, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

NE (1)