Clinical trial NCT05836831: Indian Trial of Tranexamic Acid in Spontaneous Intracerebral Haemorrhage
Official title: Indian Trial of Tranexamic Acid in Spontaneous Intracerebral Haemorrhage
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Intracerebral Hemorrhagic Stroke
Keywords: Stroke
Spontaneous Intracerebral Haemorrhage
Tranexamic acid
Lead sponsor: Christian Medical College and Hospital, Ludhiana, India
Sponsor class: OTHER
Collaborators: name: Indian Council of Medical Research
name: Sree Chitra Tirunal Institute for Medical Sciences & Technology
name: Post Graduate Institute of Medical Education and Research, Chandigarh
name: St. Stephen's Hospital, Delhi
name: All India Institute of Medical Sciences
name: Amrita Institute of Medical Sciences & Research Center
name: Kasturba Medical College Manipal, India
name: Institute of Neurosciences Kolkata
name: Bangur Institute of Neurosciences Kolkata, India
name: Guwahati Neurological Research Center, Guwahati, India
name: Baptist Christian Hospital, Tezpur, India
name: National Institute of Mental Health and Neuro Sciences, India
name: Jawaharlal Institute of Postgraduate Medical Education & Research
name: Christian Medical College, Vellore, India
name: CARE Hospitals Hyderabad, India
name: Lalitha Super Specialities Hospital Guntur, India
name: Dr. Ramesh Cardiac and Multispeciality Hospital Guntur, India
name: Government General Hospital Guntur, India
name: Fortis Escorts Hospital Jaipur, India
name: Institute of Medical Sciences of the Banaras Hindu University (BHU),India
name: Atal Institute of Medical Super Specilities, (AIMSS) Chamiana, Shimla
name: All India Institute of Medical Sciences, Bhubaneswar
name: KLEs Dr. Prabhakar Kore Hospital & Medical Research Centre Balgaum, India
name: Guru Gobind Singh Medical College & Hospital
name: PBM Hospital Bikaner, India
name: Shree Krishna Hospital Pramukhswami Medical College Anand, India
name: Apollo Excelcare Hospitals Guwahati, India
name: Manipal Hospital Bangalore, India
name: Artemis Hospital Gurgaon, India
name: Dr. Kamakshi Memorial Hospital Chennai, India
name: Bharati Vidyapeeth DTU Medical College Pune, India
name: Aster MIMS Hospital Calicut, India
name: Holy Spirit Hospital Mumbai, India
name: Sparsh Superspeciality Hospital Bangalore, India
name: King George's Medical University, Lucknow, India
name: Assam Medical College, Dibrugarh, India
name: KG Hospital and Post Graduate Medical Institute Coimbatore, India
name: Tirunelveli Medical College, Tirunelveli, India
name: Santokba Durlabhji Memorial Hospital, Jaipur, India
name: Tezpur Medical College and Hospital, Assam, India
name: Baby Memorial Hospital Calicut, India
name: Institute of Human Behaviour and Allied Sciences Delhi, India
name: The Calcutta Medical Research Institute, Kolkata, India
name: Fortis Hospital Mulund Mumbai, India
name: Government Medical College Trivandrum, India
name: Ruby Hall Clinic, Pune, India
name: Manipal Hospital Goa, India
First posted: 2023-05-01
Enrollment: 3400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicentric, randomized, open-label, clinical trial
Primary purpose: TREATMENT

Brief summary: This multicenter, pragmatic randomized, open-label clinical trial aims to assess whether Tranexamic Acid improves outcomes in adult patients with spontaneous intracerebral haemorrhage.

The participants presenting within 4.5 hours of the onset of symptoms of stroke with intracerebral haemorrhage confirmed on Computed Tomography (CT Scan) will be randomized into two groups in a 1:1 ratio using a central online randomization. The treatment arm will consist of giving intravenously 2 grams of Tranexamic Acid in 100 ml 0.9% sodium chloride administered over 45 minutes. Control arm patients will receive standard of care treatment as per the institutional protocol. In both arms, intensive systolic blood pressure reduction to less than 140 mmHg will be done using antihypertensive medications, which has to be achieved within one hour and will be maintained over next seven days. The choice of antihypertensive drug will depend on the clinician's preference.

Both groups will have a repeat CT scan after 24 hours to check for any increase in the haematoma volume. Any deterioration in the neurological status will warrant urgent brain imaging. On day 7, the patient will be assessed for their NIHSS score and mRS score. On day 90, quality of life and the functional outcome will be assessed.

Detailed description: Global Burden of Disease, Injury and Risk factors for hemorrhagic stroke 2010 estimated the burden of spontaneous intracranial haemorrhage (sICH) in India is profound (32 -49%) and it is associated with high mortality (up to 63 %) due to haematoma expansion which occurs in 38% of ICH within first few hours of presentation. Early administration of haemostatic drugs has been used in patients with trauma and was associated with improved outcomes. Similarly, if haemostatic drugs are administered early, which can be a simple and cost-effective intervention, may improve the functional outcomes in patients with sICH. Recently, the Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH 2 trial), which was done to see the effectiveness of the administration of tranexamic acid on hematoma expansion and functional outcomes at three months in patients who presented with sICH within 8 hours of presentation of symptoms onset, showed a decrease in haematoma expansion but no improvement in functional outcome at 90 days. Further larger randomized control trials are required to ascertain the effect of early administration of Tranexamic acid (TXA) in sICH. In India patients present to hospitals in the early stages that have developed symptoms after sICH and we propose to study the effect of intravenous Tranexamic Acid for hyperacute primary intracerebral haemorrhage within 4.5 hours of sICH.

Trial Population:

This multi-centric study will be conducted at 50 stroke centres in India associated with the INSTRuCT Network. All patients presenting with symptoms of stroke to the hospital and admitted to the stroke units will be screened for eligibility and if met, will be included in the study. The INTRINSIC trial intends to recruit 3400 patients.

Trial Design:

INTRINSIC Trial will be a multicenter, randomized, open-label, clinical trial. The participants will be randomized into two groups in a 1:1 ratio using a central database of INSTRuCT central online randomization. The baseline characteristics will be adjusted to stroke severity using the NIHSS score and the volume of haematoma. The treatment arm will consist of giving intravenously 2 grams of Tranexamic Acid in 100 ml sodium chloride 0.9 % administered over 45 minutes. Control arm patients will receive standard of care management as per the institutional protocol. Both groups will have a repeat CT scan after 24 hours to check for any increase in the haematoma volume. Any deterioration in the Glasgow Coma Scale (GCS) will warrant urgent brain CT scans. Antihypertensive drugs used and their doses to control BP will be recorded for up to 7 days. On day 7, the patient will be assessed for their NIHSS score and mRS score. On day 90, quality of life and the functional outcome will be assessed.

The need for this study:

The proportion of ICH is high in India and other LMIC's, particularly in Asia. Currently, there are no effective treatments available for sICH. Moreover, Tranexamic Acid is cheap, easily available and easy to administer.

Eligibility criteria: Inclusion Criteria:

Adult patients aged more than 18 years, presenting with non- traumatic intracerebral haemorrhage within 4.5 hours of onset of stroke symptoms

Exclusion Criteria:

1. Patients with intracerebral haemorrhage secondary to anticoagulation, thrombolysis, known underlying structural abnormality such as arteriovenous malformation, aneurysm, tumour or venous thrombosis or due to known hereditary coagulation disorders. An underlying structural abnormality does not need to be excluded before enrolment, but where known, patients should not be recruited.
2. Known allergies to Tranexamic Acid.
3. Premorbid modified Rankin scale score \>4 at the time of enrollment.
4. Concurrent participation in another drug or device trial.
5. Pre stroke life expectancy \<3 months (e.g. advanced metastatic cancer).
6. Glasgow coma scale \<7.
7. ICH secondary to trauma.
8. Women pregnant, or breastfeeding at randomization.
9. Planned surgery for ICH within 24 hours.
10. Concurrent or planned treatment with any other haemostatic agents.
11. ICH volume \> 60 ml as measured by the ABC/2 method on CT Scan (The size of the haematoma will be calculated by the ABC method using the formula (A x B x C)/2, in which "A" is the largest diameter of the hematoma in the CT slice with the largest area of ICH, "B" is the largest diameter of the haemorrhage perpendicular to the line "A"; and "C" is the number of slices with haematoma times the slice thickness; this formula yields haematoma volume in cubic centimetres).

Primary outcomes:
measure: Death
timeFrame: 7 days
Secondary outcomes:
measure: Change in hematoma volume
timeFrame: 24 hours
measure: Neurological impairment
timeFrame: 7 days
measure: modified Rankin Scale (mRS)
timeFrame: 90 days
measure: Quality of life EQ-5D
timeFrame: 90 days
Other outcomes:
Locations:
city: Guntur
country: India
facility: Government General Hospital
state: Andhra Pradesh
city: Guntur
country: India
facility: Lalitha Super Specialty Hospital
state: Andhra Pradesh
city: Guntur
country: India
facility: Dr Ramesh Cardiac and Multispecialty Hospital
state: Andhra Pradesh
city: Dibrugarh
country: India
facility: Assam Medical College
state: Assam
city: Guwahati
country: India
facility: Guwahati Neurological Research Center
state: Assam
city: Guwahati
country: India
facility: Apollo Excelcare Hospitals
state: Assam
city: Tezpur
country: India
facility: Baptist Christian Hospital
state: Assam
city: Tezpur
country: India
facility: Tezpur Medical College and Hospital
state: Assam
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
state: Delhi
city: New Delhi
country: India
facility: Institute of Human Behaviour and Allied Sciences
state: Delhi
city: Panjim
country: India
facility: Manipal Hospital
state: Goa
city: Anand
country: India
facility: Shree Krishna Hospital Pramukhswami Medical College
state: Gujarat
city: Gurgaon
country: India
facility: Artemis Hospital
state: Haryana
city: Bilāspur
country: India
facility: All India Institute of Medical Sciences
state: Himachal Pradesh
city: Shimla
country: India
facility: Atal Institute of Medical Super Specilities, (AIMSS) Chamiana
state: Himachal Pradesh
city: Bangalore
country: India
facility: Manipal Hospital
state: Karnataka
city: Bangalore
country: India
facility: Sparsh Superspeciality Hospital
state: Karnataka
city: Bangalore
country: India
facility: National Institute of Mental Health and Neuro-Sciences
state: Karnataka
city: Belgaum
country: India
facility: KLE's Dr. Prabhakar Kore Hospital & Medical Research Centre
state: Karnataka
city: Manipala
country: India
facility: Kasturba Medical College Manipal
state: Karnataka
city: Calicut
country: India
facility: Baby Memorial Hospital
state: Kerala
city: Calicut
country: India
facility: ASTER MIMS Hospital
state: Kerala
city: Kochi
country: India
facility: Amrita Institute for Medical Sciences and Research Center
state: Kerala
city: Thiruvananthapuram
country: India
facility: Government Medical College Trivandrum
state: Kerala
city: Thiruvananthapuram
country: India
facility: Sree Chitra Tirunal Institute for Medical Sciences and Technology
state: Kerala
city: Mumbai
country: India
facility: Fortis Hospital Mulund
state: Maharashtra
city: Mumbai
country: India
facility: Holy Spirit Hospital
state: Maharashtra
city: Pune
country: India
facility: Ruby Hall Clinic
state: Maharashtra
city: Pune
country: India
facility: Bharati Vidyapeeth DTU Medical College
state: Maharashtra
city: Bhubaneswar
country: India
facility: All India Institute of Medical Sciences
state: Orissa
city: Farīdkot
country: India
facility: Guru Gobind Singh Medical College and Hospital
state: Punjab
city: Ludhiāna
country: India
facility: Christian Medical College and Hospital, Ludhiana, Punjab
state: Punjab
city: Bīkaner
country: India
facility: PBM Hospital
state: Rajasthan
city: Jaipur
country: India
facility: Santokba Durlabhji Memorial Hospital
state: Rajasthan
city: Jaipur
country: India
facility: Fortis Escorts Hospital
state: Rajasthan
city: Chennai
country: India
facility: Dr. Kamakshi Memorial Hospital
state: Tamil Nadu
city: Coimbatore
country: India
facility: KG Hospital and Post Graduate Medical Institute Coimbatore
state: Tamil Nadu
city: Puducherry
country: India
facility: Jawaharlal Institute of Postgraduate Medical Education and Research
state: Tamil Nadu
city: Tirunelveli
country: India
facility: Tirunelveli Medical College
state: Tamil Nadu
city: Vellore
country: India
facility: Christian Medical College Vellore
state: Tamil Nadu
city: Hyderabad
country: India
facility: CARE Hospitals
state: Telangana
city: Lucknow
country: India
facility: King George's Medical University
state: Uttar Pradesh
city: Varanasi
country: India
facility: Institute of Medical Sciences of the Banaras Hindu University (BHU)
state: Uttar Pradesh
city: Kolkata
country: India
facility: Institute of Neurosciences
state: West Bengal
city: Kolkata
country: India
facility: Bangur Institute of Neurosciences
state: West Bengal
city: Kolkata
country: India
facility: The Calcutta Medical Research Center
state: West Bengal
city: Chandigarh
country: India
facility: Postgraduate Institute for Medical Education and Research
city: Delhi
country: India
facility: St Stephen's Hospital
Study officials:
affiliation: Christian Medical College and Hospital, Ludhiana, Punjab, India
name: Jeyaraj D Pandian, MD DM
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Meretoja A, Churilov L, Campbell BC, Aviv RI, Yassi N, Barras C, Mitchell P, Yan B, Nandurkar H, Bladin C, Wijeratne T, Spratt NJ, Jannes J, Sturm J, Rupasinghe J, Zavala J, Lee A, Kleinig T, Markus R, Delcourt C, Mahant N, Parsons MW, Levi C, Anderson CS, Donnan GA, Davis SM. The spot sign and tranexamic acid on preventing ICH growth--AUStralasia Trial (STOP-AUST): protocol of a phase II randomized, placebo-controlled, double-blind, multicenter trial. Int J Stroke. 2014 Jun;9(4):519-24. doi: 10.1111/ijs.12132. Epub 2013 Aug 26.