Tranexamic acid (and Desmopressin) for very early bleeds in the brain
| ISRCTN | ISRCTN97695350 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN97695350 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | 2021-001050-62 |
| Integrated Research Application System (IRAS) | 297457 |
| Protocol serial number | IRAS 297457, HTA - NIHR129917 |
| Sponsor | University of Nottingham |
| Funders | National Institute for Health Research, Programme Hospitalier de Recherche Clinique |
- Submission date
- 11/05/2021
- Registration date
- 21/06/2021
- Last edited
- 23/02/2026
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Circulatory System
Plain English summary of protocol
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 (TICH-3), patients taking antiplatelets and within 24 hours of the start of stroke symptoms (DASH-2)
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?
TICH-3: May 2021 to February 2028
DASH-2: February 2026 to September 2027
Who is funding the study?
TICH-3: National Institute for Health Research (NIHR) (UK) and Programme Hospitalier de Recherche Clinique (PHRC) (France)
DASH-2: National Institute of Health Research for Patient Benefit (NIHR RfPB)
Who is the main contact?
Cameron Skinner
cameron.skinner@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 |
|---|---|
| cameron.skinner@nottingham.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Pragmatic phase III prospective blinded randomized placebo-controlled trial |
| Secondary study design | Randomised controlled trial |
| Scientific title | Tranexamic acid for hyperacute primary intracerebral haemorrhage (TICH-3) and Desmopressin for reversal of Antiplatelet drugs in Stroke due to haemorrhage (DASH)-2 |
| Study acronym | TICH-3 / DASH-2 |
| Study objectives | Current study objectives as of 23/02/2026: Does tranexamic acid (TXA) improve outcomes when given within 4.5 hours after intracerebral haemorrhage (ICH)? For patients also taking antiplatelets, does desmopressin improve outcomes when given 24 hours after intracerebral haemorrhage (ICH)? Either independently or in combination with TXA. _____ Previous study objectives: Does tranexamic acid (TXA) improve outcomes when given within 4.5 hours after intracerebral haemorrhage (ICH)? |
| Ethics approval(s) | 1. 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 2. Approved 15/01/2026, East Midlands - Nottingham 2 REC (Health Research Authority, Redman Place, Stratford, London, E20 1 JQ, United Kingdom; 0207 104 8000; nottingham2.rec@hra.nhs.uk), ref: 21/EM/0243 |
| Health condition(s) or problem(s) studied | Hyperacute primary intracerebral haemorrhage (stroke) |
| Intervention | Current interventions as of 23/02/2026: 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. Master Protocol (TICH-3) 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. Optional sub-study (DASH-2) where participants are randomised to receive intravenous desmopressin given as 20 μg in 50 ml Sodium Chloride 0.9% over 20 minutes or a placebo (normal saline 0.9%) administered by an identical regimen. Randomisation will be to desmopressin vs placebo in a 1:1 ratio. _____ Previous interventions: 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 |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Tranexamic acid, desmopressin |
| Primary outcome measure(s) |
Current primary outcome(s) as of 23/02/2026: |
| Key secondary outcome measure(s) |
Current key secondary outcome(s) as of 23/02/2026: |
| Completion date | 01/02/2028 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | All |
| Target sample size at registration | 5500 |
| Key inclusion criteria | Current key inclusion criteria as of 23/02/2026: TICH-3: Adult patients with ICH confirmed on brain imaging within 4.5 hours of symptom onset DASH-2: Adult patients taking antiplatelets with ICH confirmed on brain imaging within 24 hours of symptom onset _____ Previous key inclusion criteria: Adult patients with ICH confirmed on brain imaging within 4.5 hours of symptom onset |
| Key exclusion criteria | Current key exclusion criteria as of 23/02/2026: TICH-3 comparison: 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 DASH-2 comparison: 1. Massive ICH for which haemostatic treatment seems futile (This would ordinarily be when haematoma volume is estimated as larger than 60ml (+/-10%)) 2. Aneurysmal subarachnoid haemorrhage 3. Haemorrhage known to be due to transformation of infarction 4. Haemorrhage known to be due to a thrombolytic drug, 5. Haemorrhage known to be due to venous thrombosis, 6. Risk/s of fluid retention associated with desmopressin judged clinically significant by the attending physician (for example patients with pulmonary oedema and/or cardiac failure), 7. Significant hypotension (systolic blood pressure <90mmHg), 8. Known drug-eluting coronary artery stent in previous three months, 9. Known unstable angina or acute coronary syndrome in past month, 10. Known allergy to desmopressin, 11. Pregnant or breast-feeding, 12. Life expectancy less than four hours, or planned for palliative care only 13. Glasgow coma scale less than 5. 14. Use of substances that are known to induce syndrome of inappropriate ADH section (SIADH), for example, tricyclic antidepressants, selective serotonin re-uptake inhibitors, chlorpromazine and carbamazepine, may cause an additive antidiuretic effect leading to increased rick of water retention and/or hyponatremia. _____ Previous 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 |
| Date of first enrolment | 23/03/2022 |
| Date of final enrolment | 01/08/2027 |
Locations
Countries of recruitment
- United Kingdom
- England
- Scotland
- Wales
- Denmark
- France
- Georgia
- Ireland
- Italy
- Malaysia
- Spain
- Sweden
- Switzerland
Study participating centres
Luton
LU4 0DZ
England
Enniskillen
BT74 6DN
Northern Ireland
Torquay
TQ2 7AA
England
Brixton
London
SE5 9RS
England
Morriston
Swansea
SA6 6NL
Wales
Derby
DE22 3NE
England
Yeovil
BA21 4AT
England
Belfast
BT12 6BA
Northern Ireland
Harrow
HA1 3UJ
England
Bretton Gate
Bretton
Peterborough
PE3 9GZ
England
Upton
Wirral
CH49 5PE
England
Salford
Manchester
M6 8HD
England
Southampton
SO16 6YD
England
Newcastle-upon-Tyne
NE1 4LP
England
London
SW17 0QT
England
London
E1 1BB
England
Stoke-on-Trent
ST4 6QG
England
Kirkcaldy
KY2 5AH
Scotland
Taunton
TA1 5DA
England
Exeter
EX2 5DW
England
Gloucester
GL1 3NN
England
Old Dalkeith Road
Edinburgh
EH16 4SA
Scotland
Bath
BA1 3NG
England
Bury St. Edmunds
IP33 2QZ
England
Nottingham
NG5 1PB
England
Portadown
BT63 5QQ
Northern Ireland
Watford
WD18 0HB
England
Westbury-on-trym
Bristol
BS10 5NB
England
Sheffield
S10 2JF
England
Middlesbrough
TS4 3BW
England
Crewe
CW1 4QJ
England
Fulwood
Preston
PR2 9HT
England
Northampton
NN1 5BD
England
Chester
CH2 1UL
England
Glasgow
G4 0SF
Scotland
Sunderland
SR4 7TP
England
Orpington
BR6 8ND
England
Bradford
BD9 6RJ
England
Westcliff-on-Sea
SS0 0RY
England
London
NW1 2BU
England
Aberdeen
AB25 2ZN
Scotland
Canterbury
CT1 3NG
England
Fulham Palace Rd
London
W6 8RF
England
Newry
BT35 8DR
Northern Ireland
Bath
BA1 3NG
England
Edgbaston
Birmingham
B15 2TH
England
Brighton
BN2 5BE
England
Bury
BL9 7TD
England
Cambridge
CB2 0QQ
England
Liverpool Road
Chester
CH2 1UL
England
Dorchester
DT1 2JY
England
Longfleet Road
Poole
BH15 2JB
England
Dryburn Hospital
North Road
Durham
DH1 5TW
England
High Wycombe
HP11 2TT
England
Leeds
LS1 3EX
England
Prescot Street
Liverpool
L7 8XP
England
Leicester
LE1 5WW
England
London
WC1N 3BG
England
Eaglestone
Milton Keynes
MK6 5LD
England
King's Lynn
PE30 4ET
England
Antrim
BT41 2RL
Northern Ireland
Londonderry
BT47 6SB
Northern Ireland
Cramlington
NE23 6NZ
England
Colney
Norwich
NR4 7UY
England
Derriford
Plymouth
PL6 8DH
England
London Road
Reading
RG1 5AN
England
Romford
RM7 0AG
England
Salisbury
SP2 8BJ
England
Dundee
DD1 9SY
Scotland
Airdrie
ML6 0JS
Scotland
Hardwick Road
Stockton-on-tees
TS19 8PE
England
Sunderland
SR4 7TP
England
Portsmouth Road
Frimley
Camberley
GU16 7UJ
England
Marlborough Road
Swindon
SN3 6BB
England
Caradoc Road
Aberystwyth
SY23 1ER
Wales
York
YO31 8HE
England
Wakefield
WF1 4DG
England
Dorking Road
Epsom
KT18 7EG
England
Lincoln
LN2 5QY
England
Heath Town
Wolverhampton
WV10 0QP
England
Basildon
SS16 5NL
England
Carlisle
CA2 7HY
England
Truro
TR1 3LJ
England
Coventry
CV2 2DX
England
Dartford
DA2 8DA
England
Doncaster
DN2 5LT
England
Eastbourne
BN21 2UD
England
Ipswich
IP4 5PD
England
Hull
HU3 2JZ
England
Rhyl
LL18 3AS
Wales
Sutton-in-Ashfield
NG17 4JL
England
Dafen
Llanelli
SA14 8QF
Wales
Winchester
SO22 5DG
England
Bodelwyddan
Rhyl
LL18 5UJ
Wales
Cardiff
CF14 4XW
Wales
East Kilbride
G75 8RG
Scotland
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Stored in repository |
| 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? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| 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 |
| Study website | Study website | 11/11/2025 | 11/11/2025 | No | Yes |
Additional files
- ISRCTN97695350_PROTOCOL_V2.0_07Oct22.pdf
- Protocol file
- ISRCTN97695350_PROTOCOL_V4.2_30Mar23.pdf
- Protocol for the CTIS EU countries
Editorial Notes
23/02/2026: The following changes were made to the study record:
1. The public title was changed from "Tranexamic acid for very early bleeds in the brain" to "Tranexamic acid (and Desmopressin) for very early bleeds in the brain".
2. The scientific title was changed from "Tranexamic acid for hyperacute primary intracerebral haemorrhage (TICH-3)" to "Tranexamic acid for hyperacute primary intracerebral haemorrhage (TICH-3) and Desmopressin for reversal of Antiplatelet drugs in Stroke due to haemorrhage (DASH)-2".
3. The study acronym was changed from TICH-3 to TICH-3 / DASH-2.
4. The study objectives were changed.
5. The ethics approval (2) was added.
6. The interventions were changed.
7. The drug name was changed from Tranexamic acid to Tranexamic acid, desmopressin.
8. The primary outcome(s) were changed.
9. The key secondary outcome(s) were changed.
10. The key inclusion criteria were changed.
11. The key exclusion criteria were changed.
12. The study participating centres were updated.
13. Contact details updated.
14. The plain English summary was updated to reflect these changes.
05/11/2025: The study participating centres were updated.
14/10/2025: The study participating centres were updated.
28/08/2025: Rigshospitalet and Presidio Ospedale San Carlo were added as study participating cenrtes.
11/08/2025: University Hospital Hairmyres was added to the study participating centres.
05/08/2025: The study participating centre University Hospital of Wales was added.
24/07/2025: The study participating centres Hôpital Jean Minjoz, CHU Dijon Bourgogne, CHU Lyon, Hôpital Nord Laennec, Centre Hospitalier Sud Francilien, Hôpital Universitaire de la Pitié-Salpêtrière, Hôpital Lariboisière, Hôpital Pellegrin Bordeaux, Centre Hospitalier Sainte‐Anne, Hôpital Foch, Hôpital André Mignot, CHU Poitiers, CHU Rouen and Hôpital Pierre Paul Riquet were added.
23/07/2025: The study participating centres LTD Urgent Neurological Clinic Neurology, ASST Ovest Milanese, Presidio Ospedale San Carlo, Azienda USL Toscana Nord Ovest, Klinik Hirslanden were added.
22/07/2025: The study participating centre Glan Clwd Hospital was added.
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.
