Tranexamic acid for very early bleeds in the brain
| ISRCTN | ISRCTN97695350 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN97695350 |
| EudraCT/CTIS number | 2021-001050-62 |
| IRAS number | 297457 |
| Secondary identifying numbers | IRAS 297457, HTA - NIHR129917 |
- Submission date
- 11/05/2021
- Registration date
- 21/06/2021
- Last edited
- 28/08/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Circulatory System
Plain English Summary
Background and study aims
Tranexamic acid is a standard treatment in bleeding emergencies such as trauma and childbirth, where it reduces deaths from bleeding. A recent study showed that tranexamic acid given within 8 hours of a bleed on the brain is safe and prevents hematoma (abnormal collection of blood) growth. There was also a small reduction in the number of patients who died within the first 7 days. The study was not large enough to show whether there were effects on long-term disability. Tranexamic acid is cheap (£12) and easy to administer. If it is effective it could make a difference to patients with a bleed on the brain and their families worldwide.
The researchers have worked closely with stroke survivors and their carers to design this study. They told them that increased survival is important, but most people would not want to be alive at the expense of very severe disability, and also that 3 months is too early to measure recovery after stroke 6 months is more appropriate. The researchers discussed emergency consent in detail, and their advisors suggested that most people would be happy with the emergency consent procedure for this study. They also would prefer a blinded study where participants do not know which treatment they receive.
Who can participate?
Patients most likely to benefit from the treatment - those within 4.5 hours of the start of stroke symptoms
What does the study involve?
Patients will be approached about the study in the emergency department as soon as the brain scan confirms bleeding in the brain. The patient will be asked if they want to take part in the study; if they agree, a computer will decide, akin to the toss of a coin, whether they get an injection of tranexamic acid into a vein, or whether they receive saltwater as a placebo. The researchers will use a rapid emergency consent process, in accordance with ethical guidelines. It will be decided by chance which treatment the participants receive and it will not be possible for the doctor or the patient to know if they receive the tranexamic acid or placebo as the treatment packs look identical. It will be one injection, and then normal standard care will be given. The researchers will also contact people at 6 months after their stroke to assess their recovery and quality of life.
What are the possible benefits and risks of participating?
Tranexamic acid may stop participants from having a further bleed and may help them recover from the stroke but this is not guaranteed. The results of the study will help the treatment of stroke patients in the future. A risk of seizures has been demonstrated with tranexamic acid use in cardiac surgery where high doses of TXA are used. The proposed dose for this study is well below the dose associated with increased seizure risk. A recent traumatic brain injury study demonstrated a reduced death rate in patients given tranexamic acid. A recent study also revealed no increased risk of thromboembolic events (blood clots).
Where is the study run from?
University of Nottingham (UK)
When is the study starting and how long is it expected to run for?
May 2021 to February 2028
Who is funding the study?
National Institute for Health Research (NIHR) (UK) and Programme Hospitalier de Recherche Clinique (PHRC) (France)
Who is the main contact?
Dr Tiffany Hamilton
tiffany.hamilton@nottingham.ac.uk
Contact information
Scientific
Stroke Trials Unit
Mental Health & Clinical Neurosciences
University of Nottingham
D Floor, South Block, Room 2106
Queens Medical Centre
Nottingham
NG7 2UH
United Kingdom
 ORCID ID |
0000-0002-5871-8168 |
|---|---|
| Phone | +44 (0)115 823 1778 |
| nikola.sprigg@nottingham.ac.uk |
Scientific
The Stroke Trials Unit
University of Nottingham
D Floor South Block
Queens Medical Centre
Nottingham
NG7 2UH
United Kingdom
| Phone | +44 (0)115 8231060 |
|---|---|
| tiffany.hamilton@nottingham.ac.uk |
Study information
| Study design | Pragmatic phase III prospective blinded randomized placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | Tranexamic acid for hyperacute primary intracerebral haemorrhage (TICH-3) |
| Study acronym | TICH-3 |
| Study hypothesis | Does tranexamic acid (TXA) improve outcomes when given within 4.5 hours after intracerebral haemorrhage (ICH)? |
| Ethics approval(s) | Approved 17/11/2021, East Midlands - Nottingham 2 REC (Equinox House, City Link, Nottingham, NG2 4LA, UK; +44 (0)207 104 8169; Nottingham2.rec.nra.nhs.uk), ref: 21/EM/0243 |
| Condition | Hyperacute primary intracerebral haemorrhage (stroke) |
| Intervention | Pragmatic phase III prospective blinded randomised placebo-controlled trial performed in two phases: a 30-month internal pilot phase with pre-specified progression criteria then the main phase. Using a pragmatic design with emergency consent processes, simple randomisation and minimal data collection will optimise enrolment and the blinded design will minimise bias. Participants are randomised to receive intravenous TXA 2 g given as 1 g bolus in 100 ml normal saline 0.9% infusion over 10 min and 1 g infusion in 250 ml normal saline 0.9% over 8 hours or a placebo (normal saline 0.9%) administered by an identical regimen. Randomisation will be to TXA vs placebo in a 1:1 ratio. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Tranexamic acid |
| Primary outcome measure | Death at 7 days, measured by the number of participants who have died by Day 7 |
| Secondary outcome measures | 1. Disability measured by modified Rankin Scale (mRS) at Day 180 2. Venous thromboembolism/ischaemic events/seizures measured by review of medical notes at Day 7 3. Quality of life measured by EQ-5D visual analogue score (VAS) at Day 180 4. Cognition measured by AD-8 at Day 180 5. Health economics (use of antihypertensive medication, Do Not Resuscitate orders, admission to intensive care, neurosurgical intervention, hospital length of stay and discharge disposition) measured by review of medical notes at Day 180 |
| Overall study start date | 01/05/2021 |
| Overall study end date | 01/02/2028 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 5500 |
| Participant inclusion criteria | Adult patients with ICH confirmed on brain imaging within 4.5 hours of symptom onset |
| Participant exclusion criteria | Current participant exclusion criteria as of 01/03/2023: 1. Patient with a known indication for TXA treatment (e.g. traumatic brain injury) 2. Patient with contraindication for TXA treatment 3. Patient known to be taking therapeutic anticoagulation with warfarin or low molecular weight heparin at the time of enrolment. Patients taking direct oral anticoagulants can be included and are not excluded. 4. Massive ICH for which haemostatic treatment seems futile (This would ordinarily be when haematoma volume is estimated as larger than 60ml) 5. Severe coma (Glasgow Coma Scale <5) 6. Decision was already taken for palliative (end of life) care with the withdrawal of active treatment Previous participant exclusion criteria: 1. Indication for TXA 2. Patient known to be taking anti-coagulation 3. Glasgow Coma Scale (GCS) <5 4. Estimated haematoma volume (HV) >60 ml 5. Palliative care |
| Recruitment start date | 23/03/2022 |
| Recruitment end date | 01/08/2027 |
Locations
Countries of recruitment
- Denmark
- England
- France
- Georgia
- Ireland
- Italy
- Malaysia
- Northern Ireland
- Scotland
- Spain
- Sweden
- Switzerland
- United Kingdom
- Wales
Study participating centres
Luton
LU4 0DZ
United Kingdom
Enniskillen
BT74 6DN
United Kingdom
Torquay
TQ2 7AA
United Kingdom
Brixton
London
SE5 9RS
United Kingdom
Morriston
Swansea
SA6 6NL
United Kingdom
DE22 3NE
United Kingdom
Yeovil
BA21 4AT
United Kingdom
Belfast
BT12 6BA
United Kingdom
Harrow
HA1 3UJ
United Kingdom
Bretton Gate
Bretton
Peterborough
PE3 9GZ
United Kingdom
Upton
Wirral
CH49 5PE
United Kingdom
Salford
Manchester
M6 8HD
United Kingdom
Southampton
SO16 6YD
United Kingdom
Newcastle-upon-Tyne
NE1 4LP
United Kingdom
London
SW17 0QT
United Kingdom
London
E1 1BB
United Kingdom
Stoke-on-Trent
ST4 6QG
United Kingdom
Kirkcaldy
KY2 5AH
United Kingdom
Taunton
TA1 5DA
United Kingdom
Exeter
EX2 5DW
United Kingdom
Gloucester
GL1 3NN
United Kingdom
Old Dalkeith Road
Edinburgh
EH16 4SA
United Kingdom
Bath
BA1 3NG
United Kingdom
Bury St. Edmunds
IP33 2QZ
United Kingdom
Nottingham
NG5 1PB
United Kingdom
Portadown
BT63 5QQ
United Kingdom
Watford
WD18 0HB
United Kingdom
BS10 5NB
United Kingdom
Sheffield
S10 2JF
United Kingdom
Middlesbrough
TS4 3BW
United Kingdom
Crewe
CW1 4QJ
United Kingdom
Fulwood
Preston
PR2 9HT
United Kingdom
Northampton
NN1 5BD
United Kingdom
Chester
CH2 1UL
United Kingdom
Glasgow
G4 0SF
United Kingdom
Sunderland
SR4 7TP
United Kingdom
Orpington
BR6 8ND
United Kingdom
Bradford
BD9 6RJ
United Kingdom
Westcliff-on-Sea
SS0 0RY
United Kingdom
London
NW1 2BU
United Kingdom
Aberdeen
AB25 2ZN
United Kingdom
Canterbury
CT1 3NG
United Kingdom
Fulham Palace Rd
London
W6 8RF
United Kingdom
Bandar Tun Razak
Kuala Lumpur
56000
Malaysia
42300
Malaysia
Kuala Lumpur
50586
Malaysia
Klang
41200
Malaysia
Pulau Pinang
13700
Malaysia
20400
Malaysia
93586
Malaysia
Kubang Kerian
Kota Bharu
16150
Malaysia
Serdang
43400
Malaysia
Kota Kinabalu
88200
Malaysia
Jalan Damai
Luyang Commercial Centre
Kota Kinabalu
88300
Malaysia
Bukit Rasah
Seremban
70300
Malaysia
Bandar
Alor Setar
05460
Malaysia
Johor Bahru
80100
Malaysia
Tbilisi
0141
Georgia
Tbilisi
0114
Georgia
Tbilisi
0144
Georgia
Tbilisi
0144
Georgia
Copenhagen
DK2400
Denmark
Aarhus
DK8200
Denmark
Odense
DK5000
Denmark
Servei de Farmàcia, Unitat d'Assaigos Clínics (UAC), planta sòtan -1
Ps. Vall d'Hebron 119
Barcelona
08035
Spain
Carrer Sant Quintí 89
Barcelona
08025
Spain
Servei de Farmàcia, Planta SS
Av. de França s/n
Girona
17007
Spain
Servicio de Farmacia, planta -3 derecha
Carretera de Colmenar km 9.1
Madrid
28034
Spain
Servicio de Farmacia, planta -1
As Xubias, 84
A Coruña
15006
Spain
Servicio de Farmacia, planta -2
Av. Ramón y Cajal, 3
Valladolid
47003
Spain
Gldani-Nadzaladevi district
Tbilisi
0192
Georgia
Beaumont Road
Dublin
D09 V2N0
Ireland
Cork
T12 DC4A
Ireland
Dublin
D07 R2WY
Ireland
Saint James' (part of Phoenix Park)
Dublin
D08 NHY1
Ireland
Dublin
D04 T6F4
Ireland
Tallaght
Dublin
D24 NR04
Ireland
Dooradoyle
Limerick
V94 F858
Ireland
Waterford
X91 ER8E
Ireland
Mantova
46100
Italy
Bergamo
24127
Italy
Napoli
80131
Italy
Selargius
Cagliari
09047
Italy
Brescia
25123
Italy
Milano
20162
Italy
Lecco
23900
Italy
Rome
00152
Italy
Via Branca
Gubbio
Perugia
06024
Italy
Castello
06012
Italy
Newry
BT35 8DR
United Kingdom
Bath
BA1 3NG
United Kingdom
Edgbaston
Birmingham
B15 2TH
United Kingdom
Brighton
BN2 5BE
United Kingdom
Bury
BL9 7TD
United Kingdom
Cambridge
CB2 0QQ
United Kingdom
Liverpool Road
Chester
CH2 1UL
United Kingdom
Dorchester
DT1 2JY
United Kingdom
Longfleet Road
Poole
BH15 2JB
United Kingdom
Dryburn Hospital
North Road
Durham
DH1 5TW
United Kingdom
High Wycombe
HP11 2TT
United Kingdom
Leeds
LS1 3EX
United Kingdom
Prescot Street
Liverpool
L7 8XP
United Kingdom
Leicester
LE1 5WW
United Kingdom
London
WC1N 3BG
United Kingdom
Eaglestone
Milton Keynes
MK6 5LD
United Kingdom
King's Lynn
PE30 4ET
United Kingdom
Antrim
BT41 2RL
United Kingdom
Londonderry
BT47 6SB
United Kingdom
Cramlington
NE23 6NZ
United Kingdom
Colney
Norwich
NR4 7UY
United Kingdom
Derriford
Plymouth
PL6 8DH
United Kingdom
London Road
Reading
RG1 5AN
United Kingdom
Romford
RM7 0AG
United Kingdom
Salisbury
SP2 8BJ
United Kingdom
Dundee
DD1 9SY
United Kingdom
Airdrie
ML6 0JS
United Kingdom
Hardwick Road
Stockton-on-tees
TS19 8PE
United Kingdom
Sunderland
SR4 7TP
United Kingdom
Portsmouth Road
Frimley
Camberley
GU16 7UJ
United Kingdom
Marlborough Road
Swindon
SN3 6BB
United Kingdom
Caradoc Road
Aberystwyth
SY23 1ER
United Kingdom
York
YO31 8HE
United Kingdom
Wakefield
WF1 4DG
United Kingdom
Dorking Road
Epsom
KT18 7EG
United Kingdom
Lincoln
LN2 5QY
United Kingdom
Heath Town
Wolverhampton
WV10 0QP
United Kingdom
Basildon
SS16 5NL
United Kingdom
Carlisle
CA2 7HY
United Kingdom
Truro
TR1 3LJ
United Kingdom
Coventry
CV2 2DX
United Kingdom
Dartford
DA2 8DA
United Kingdom
Doncaster
DN2 5LT
United Kingdom
Eastbourne
BN21 2UD
United Kingdom
Ipswich
IP4 5PD
United Kingdom
Hull
HU3 2JZ
United Kingdom
Rhyl
LL18 3AS
United Kingdom
Sutton-in-Ashfield
NG17 4JL
United Kingdom
Dafen
Llanelli
SA14 8QF
United Kingdom
Winchester
SO22 5DG
United Kingdom
4, Gudamakari str.
Tbilisi
0141
Georgia
UKM Medical Centre
Tuanku Muhriz, Jalan Yaacob Latif
Bandar Tun Razak 56000, Cheras
Federal Territory Kuala Lumpur
56000
Malaysia
Bispebjerg Hospital
Copenhagen
Bispebjerg Bakke 23
Denmark
ASST di Mantova
Strada Lago Paiolo, 10
Mantova
46100
Italy
Insel Gruppe AG
Inselspital
Freiburgstrasse, 8
Bern
3010
Switzerland
Haartmaninkatu 4 (P.O. Box 340)
Helsinki
FI-00029 HUS
Finland
et Pathologie Neurovasculaire
Hôpital Roger Salengro
Rue Emile Laine, Cedex
Lille
59037
France
Uppsala University Hospital
Akademiska sjukhuset
Sjukhusvägen
Uppsala
751 85
Sweden
Hospital Universitari Vall d'Hebron
Passeig de la Vall d'Hebron, 119
Barcelona
08035
Spain
Tallaght
Dublin
D24 NR0A
Ireland
Sponsor information
University/education
c/o Angela Shone
Research and Innovation
East Atrium
Jubilee Conference Centre
Triumph Road
Nottingham
NG8 1DH
England
United Kingdom
| Phone | +44 (0)115 8467906 |
|---|---|
| angela.shone@nottingham.ac.uk | |
| Website | https://www.nottingham.ac.uk/fabs/research-innovation/meettheteam/angela.shone |
"ROR" |
https://ror.org/01ee9ar58 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
No information available
Results and Publications
| Intention to publish date | 01/07/2028 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Stored in repository |
| Publication and dissemination plan | Protocol paper to be published at a later date. Simultaneous oral presentation at a large international stroke conference and publication in high impact journal. Stroke survivors and carers will inform dissemination to patients and public which is likely to include social media and a roadshow. |
| IPD sharing plan | An anonymised dataset, collected during the duration of the trial by the University of Nottingham, will be stored securely and in a password-protected database by the University of Nottingham. Individual anonymised participant data will be shared with the Virtual International Stroke Trials Archive (VISTA). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 2.0 | 07/10/2022 | 16/05/2023 | No | No |
| Protocol file | Protocol for the CTIS EU countries version 4.2 |
30/03/2023 | 16/05/2023 | No | No |
| HRA research summary | 28/06/2023 | No | No |
Additional files
- ISRCTN97695350_PROTOCOL_V2.0_07Oct22.pdf
- ISRCTN97695350_PROTOCOL_V4.2_30Mar23.pdf
- Protocol for the CTIS EU countries
Editorial Notes
28/08/2024: The following updates were made:
1. Basildon University Hospital, Cumberland Infirmary, Royal Cornwall Hospital, University Hospital Coventry, Darent Valley Hospital, Doncaster Royal Infirmary, Eastbourne General District Hospital, Ipswich Hospital, Hull Royal Infirmary, Royal Alexandra Hospital, King's Mill Hospital, Prince Philip Hospital and Royal Hampshire County Hospital were added as UK study participating sites.
2. LEPL The First University Clinic of Tbilisi State, UKM Medical Centre, Bispebjerg Hospital, ASST di Mantova, Insel Gruppe AG (Bern), Helsinki University Hospital, Hôpital Roger Salengro (Lille), Uppsala University Hospital, Hospital Universitari Vall d'Hebron and Tallaght University Hospital were added as International study participating sites.
16/05/2023: Protocol files uploaded.
01/03/2023: The following changes have been made:
1. The participant exclusion criteria have been changed.
2. The trial participating centres Epsom Hospital, and New Cross Hospital have been added.
14/06/2022: Contact details updated.
20/05/2022: The following changes have been made:
1. The recruitment start date has been changed from 01/05/2022 to 23/03/2022.
2. The ethics approval has been added.
3. A study contact has been added.
4. The trial website has been added.
06/05/2022: The trial participating centres “Royal United Hospital”, “Queen Elizabeth Hospital”, “Royal Sussex County Hospital”, “Fairfield General Hospital”, “Addenbrookes Hospital”, “Countess of Chester Hospital”, “Dorset County Hospital”, “Poole Hospital Bcsc”, “University Hospital of North Durham”, “Wycombe General Hospital”, “Leeds General Infirmary”, “Royal Liverpool University Hospital NHS Trust”, “Leicester Royal Infirmary”, “The National Hospital for Neurology and Neurosurgery”, “Milton Keynes University Hospital”, “Queen Elizabeth Hospital”, “Antrim Area Hospital”, “Altnagelvin Area Hospital”, “Northumbria Specialist Emergency Care Hospital”, “Norfolk and Norwich University Hospital”, “Derriford Hospital”, “Royal Berkshire Hospital”, “Queens Hospital”, “Salisbury District Hospital”, “Ninewells Hospital”, “Monklands District General Hospital”, “University Hospital of North Tees Tatchell Centre”, “Sunderland Royal Hospital”, “Frimley Park Hospital Laboratory”, “Great Western Hospital Laboratory”, “Bronglais General Hospital”, “York Teaching Hospital”, and “Pinderfields Hospital” have been added.
29/04/2022: The trial participating centre “Daisy Hill Hospital” has been added.
20/04/2022: The trial participating centres “Malkhaz Katsiashvili Multiprofile Emergency Medicine Center”, “Beaumount Hospital”, "Cork University Hospital", "The Mater Misericordiae University Hospital", "St. James Hospital", "St Vincents University Hospital", "Tallaght University Hospital", "University Hospital Limerick", "Univeristy Hospital Waterford", "ASST di Mantova", "ASST Papa Giovanni XXIII", "Azienda Ospedaliera di Rilievo Nazionale Antonia Cardarelli", "Azienda Ospedaliera G. Brotzu", "Bresia Civili", "ASST Grande Ospedale Metropolitano Niguarda", "Alessandro Manzoni Hospital", "San Camillo Forlanini Hospital", "The Hospital of Gubbio and Gualdo Tadino (Ospedale di Gubbio e Gualdo Tadino)", and "Ospedale Città di Castello" have been added.
21/03/2022: The EudraCT number has been added.
18/03/2022: The following changes have been made:
1. The scientific contact's details have been changed.
2. All trial sites in Malaysia, Georgia, Denmark and Spain have been added.
27/01/2022: The following changes have been made:
1. Programme Hospitalier de Recherche Clinique has been added as a funder and the plain English summary has been updated accordingly.
2. Denmark, France, Georgia, Ireland, Italy, Malaysia, Spain, Sweden, and Switzerland have been added as countries of recruitment.
13/05/2021: Trial's existence confirmed by the NIHR.
