Trial to evaluate tranexamic acid therapy in thrombocytopenia

ISRCTN	ISRCTN73545489
DOI	https://doi.org/10.1186/ISRCTN73545489
EudraCT/CTIS number	2014-001513-35
ClinicalTrials.gov number	NCT03136445
Secondary identifying numbers	CPMS 18157

Submission date: 25/03/2015
Registration date: 25/03/2015
Last edited: 01/04/2025

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-of-tranexamic-acid-for-low-platelet-counts-treatt

Study website

Contact information

Ms Claire Rourke
Scientific

NHSBT Clinical Trials Unit
Cambridge Blood Donor Centre
Long Road
Cambridge
CB2 0PT
United Kingdom

ORCID ID	0000-0002-7631-9275
Phone	+44 (0)7385 964361
Email	Claire.Rourke2@nhsbt.nhs.uk

Study information

Study design	Randomized; Interventional; Design type: Treatment
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 contact details to request a patient information sheet
Scientific title	A double blind, randomised controlled TRial EvaluAting the safety and efficacy of Tranexamic acid in patients with haematological malignancies with severe Thrombocytopenia
Study acronym	TREATT
Study hypothesis	Patients with cancers of the blood often develop low blood cell counts either as a consequence of the disease or the treatment by chemotherapy or stem cell transplantation. Platelet transfusions are commonly given to raise any low platelet count and reduce the risk of clinical bleeding (prophylaxis) or stop active bleeding (therapy). But recent studies have indicated that many patients continue to experience bleeding, despite the use of platelet transfusions. Tranexamic acid is a type of drug that is called an antifibrinolytic. These drugs act to reduce the breakdown of clots formed in response to bleeding. These drugs have been used widely in both elective and emergency surgery and have been shown to decrease blood loss and the use of red cell transfusions. The purpose of this study is to test whether giving tranexamic acid to patients receiving treatment for blood cancers reduces the risk of bleeding or death, and the need for platelet transfusions. Patients will be randomised to receive tranexamic acid (given intravenously through a drip, or orally) or a placebo. We will measure the rates of bleeding daily using a short structured assessment of bleeding, and we will record the number of transfusions given to patients.
Ethics approval(s)	South-Central Oxford C, 16/03/2015, ref: 14/SC/1290
Condition	Patients with haematological malignancies receiving intensive chemotherapy and/or stem cell transplantation
Intervention	Prophylactic TXA/Placebo, double-blind, placebo controlled parallel group trial to assess the safety and efficacy of tranexamic acid at reducing bleeding in patients with haematological malignancies and severe thrombocytopenia. Participants will be randomised to receive TXA or placebo. Trial treatment will be started as per randomisation assignment as soon as possible within 24 hours of the first recorded platelet count = 30 x 109/L. Dose schedule TXA 1g every eight hours IV or 1.5g every eight hours PO. Follow Up Length: 4 month(s); Study Entry : Single Randomisation only
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	Tranexamic acid
Primary outcome measure	Current primary outcome measure as of 10/12/2018: Estimated proportion of participants who died or had bleeding of WHO grade 2 or above during the first 30 days of the trial from the first day of trial treatment. A time-to-event analysis will be used to determine this proportion to ensure that all participants are included in the primary outcome analysis, not just those who are followed up for the full 30 days. Any participants lost to follow-up will be included in the analysis and censored at the time that they were lost. Previous primary outcome measure: Proportion of patients who died or had bleeding of WHO grade 2 or above during the first 30 days of the trial. Day 1 being the first day the patient’s platelet count falls to ≤30x109/L. A time-to-event analysis will be used to determine this proportion to ensure that all patients are included in the primary outcome analysis, not just those who are followed up for the full 30 days. Any patients lost to follow-up will be included in the analysis and censored at the time that they were lost.
Secondary outcome measures	Current secondary outcome measures as of 10/12/2018: 1. Secondary Efficacy Outcomes: All measured during first 30 days of the trial, i.e. from the first day of trial treatment. 1.1. Proportion of days with bleeding (WHO grade 2 or above) 1.2. Time to first episode of bleeding of WHO grade 2 or greater 1.3. Highest grade of bleeding a participant experiences 1.4. Number of platelet transfusions/participant 1.5. Number of red cell transfusions/participant 1.6. Proportion of participants surviving up to 30 days without a platelet transfusion 1.7. Proportion of participants surviving up to 30 days without a red cell transfusion 1.8. Quality of life, measured using EQ-5D-5L and FACT-TH18 (V4) at Day of Randomisation, Day 12, Day 30 and Day 120 2. Secondary Safety Outcomes: 2.1. Number of thrombotic events from first administration of trial treatment up to and including 120 days after the first dose of trial treatment is administered, per day at risk 2.2. Number of participants developing Veno-occlusive Disease (VOD; Sinusoidal obstructive syndrome, SOS) within 60 days of first administration of trial treatment 2.3. All-cause mortality during the first 30 days and the first 120 days after the first dose of trial treatment is administered 2.4. Death due to thrombosis during the first 120 days after the first dose of trial treatment is administered 2.5. Death due to bleeding during the first 30 days after the first dose of trial treatment is administered 2.6. Number of serious adverse events from first administration of trial treatment until 60 days after the first dose of trial treatment is administered 3. Other outcomes: All measured during first 30 days of the trial, i.e. from the first dose of trial treatment 3.1. Proportion of days with thrombocytopenia (≤10x109/L, ≤30x109/L, ≤50x109/L) 3.2. Proportion of days with fever (highest daily temperature ≥ 38.1°C) of days spent in hospital, up to study day 30 3.3. Reasons for platelet and red cell transfusions Previous secondary outcome measures: 1. Secondary Efficacy Outcomes: All measured during first 30 days of the trial. Day 1 being the first day the patient’s platelet count falls to ≤30x109/L.) 1.1. Proportion of days with bleeding (WHO grade 2 or above) 1.2. Time to first episode of bleeding of WHO grade 2 or greater for those patients who bled 1.3. Highest grade of bleeding a patient experiences 1.4. Number of platelet transfusions/patient 1.5. Number of red cell transfusions/patient 1.6. Proportion of patients surviving at least 30 days without a platelet transfusion 1.7. Proportion of patients surviving at least 30 days without a red cell transfusion 2. Secondary Safety Outcomes: 2.1. Number of thrombotic events from first administration of trial treatment up to and including 120 days after the first dose of trial treatment is administered, per day at risk 2.2. Number of patients developing Veno-occlusive Disease (VOD; Sinusoidal obstructive syndrome, SOS) within 60 days of first administration of trial treatment 2.3. All-cause mortality during the first 30 days and the first 120 days after the first dose of trial treatment is administered 2.4. Death due to thrombosis during the first 120 days after the first dose of trial treatment is administered 2.5. Death due to bleeding during the first 30 days after the first dose of trial treatment is administered 2.6. Number of serious adverse events from first administration of trial treatment until 60 days after the first dose of trial treatment is administered 3. Other outcomes: All measured during first 30 days of the trial. Day 1 being the first day the patient’s platelet count falls to ≤30x109/L.) 3.1. Number of days with thrombocytopenia (≤10x109/L, ≤30x109/L, ≤50x109/L) 3.2. Reasons for platelet and red cell transfusions
Overall study start date	30/04/2015
Overall study end date	18/06/2022

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	616
Total final enrolment	616
Participant inclusion criteria	1. At least 18 years of age 2. Confirmed diagnosis of a haematological malignancy 3. Undergoing chemotherapy or haematopoietic stem cell transplantation 4. Anticipated to have a hypoproliferative thrombocytopenia resulting in a platelet count of ≤10x10 to the power of 9/L for ≥ 5 days 5. Able to comply with treatment and monitoring
Participant exclusion criteria	Current exclusion criteria as of 10/12/2018: 1. Patients with a past history or current diagnosis of arterial or venous thromboembolic disease including myocardial infarction, peripheral vascular disease and retinal arterial or venous thrombosis 2. Diagnosis of acute promyelocytic leukaemia (APML) and undergoing induction chemotherapy 3. Patients with a diagnosis/previous history of veno-occlusive disease (also called sinusoidal obstruction syndrome) 4. Patients with known inherited or acquired prothrombotic disorders e.g. 4.1. Lupus anticoagulant 4.2. Positive antiphospholipids 5. Patients receiving any pro-coagulant agents (e.g. DDAVP, recombinant Factor VIIa or Prothrombin Complex Concentrates (PCC) within 48 hours of enrolment, or with known hypercoagulable state 6. Patients receiving L-asparaginase as part of their current cycle of treatment 7. History of immune thrombocytopenia (ITP), thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome (HUS) 8. Patients with overt DIC (See Appendix 3 in the protocol for definition) 9. Patients requiring a platelet transfusion threshold >10x109/L at time of randomisation (This refers to patients who require their platelet count to be maintained at a certain specified level on an ongoing basis, and excludes a transient rise in the threshold due to sepsis) 10. Patients with a known inherited or acquired bleeding disorder e.g. 10.1. Acquired storage pool deficiency 10.2. Paraproteinaemia with platelet inhibition 11. Patients receiving anticoagulant therapy or anti-platelet therapy 12. Patients with visible haematuria at time of randomisation 13. Patients with anuria (defined as urine output < 10 mls/hr over 24 hours) 14. Patients with severe renal impairment (eGFR ≤30 ml/min/1.73m2) 15. Patients with a previous history of epilepsy, convulsions, fits or seizures 16. Patients who are pregnant or breastfeeding 17. Allergic to tranexamic acid 18. Patients enrolled in other trials involving platelet transfusions, anti-fibrinolytics, platelet growth factors or other pro-coagulant agents 19. Patients previously randomised into this trial at any stage of their treatment Previous exclusion criteria: 1. Diagnosis of acute promyelocytic leukaemia and undergoing induction chemotherapy 2. History of ITP, TTP or HUS 3. Patients receiving L-asparginase as part of their current cycle of treatment 4. Patients with a past history or current diagnosis of arterial or venous thromboembolic disease including myocardial infarction, peripheral vascular disease and retinal arterial or venous thrombosis 5. Patients with a diagnosis/previous history of veno-occlusive disease (also called sinusoidal obstruction syndrome) 6. Patients receiving any pro-coagulant agents (e.g. DDAVP, recombinant Factor VIIa or Prothrombin Complex Concentrates (PCC) within 48 hours of enrolment, or with known hypercoagulable state 7. Known inherited or acquired bleeding disorder. E.g. acquired storage pool deficiency; paraproteinaemia with platelet inhibition; known inherited or acquired prothrombotic disorders 9. Patients receiving anticoagulant therapy or anti-platelet therapy 10. Patients with overt disseminated intravascular coagulation 11. Patients with visible haematuria at time of randomisation 12. Patients requiring a platelet transfusion threshold >10x10 to the power of 9/L at time of randomisation 13. Patients with anuria (defined as urine output < 10mls/hr over 24 hours) 14. Patients who are pregnant 15. Patients enrolled in other trials involving platelet transfusions, anti-fibrinolytics, platelet growth factors or other pro-coagulant agents 16. Allergic to tranexamic acid or epsilon amino caproic acid 17. Previously randomised in this study at any stage of their treatment
Recruitment start date	30/04/2015
Recruitment end date	18/02/2022

Locations

Countries of recruitment

Australia
England
United Kingdom

Study participating centre

John Radcliffe Hospital

National Blood Service – Oxford Centre
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom

Sponsor information

NHS Blood and Transplant (NHSBT)
Hospital/treatment centre

John Radcliffe Hospital
Headley Way
Oxford
OX3 9DU
England
United Kingdom

"ROR"	https://ror.org/0227qpa16

Funders

Funder type

Hospital/treatment centre

NHS Blood and Transplant
Government organisation / Local government

Alternative name(s): National Health Service Blood and Transplant, UK National Health Service Blood and Transplant, NHSBT
Location: United Kingdom

National Health and Medical Research Council
Government organisation / National government

Alternative name(s): NHMRC
Location: Australia

Results and Publications

Intention to publish date	31/10/2024
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Current publication and dissemination plan as of 17/07/2023: The trialists have published the protocol and will add the final results of the study once ready. Previous publication and dissemination plan: The trialists plan to publish the protocol and the final results of the study.
IPD sharing plan	The datasets generated during and/or analysed during the current study will be available upon request from the NHSBT Clinical Trials Unit after de-identification (text, tables, figures and appendices) 9 months after publication and ending 5 years following article publication. Data will be shared with investigators whose use of the data has been assessed and approved by an NHSBT review committee as a methodologically sound proposal.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article	protocol	15/10/2019	11/02/2020	Yes	No
HRA research summary			28/06/2023	No	No
Plain English results		09/01/2025	09/01/2025	No	Yes
Results article		03/12/2024	09/01/2025	Yes	No
Plain English results			20/02/2025	No	Yes

Additional files

ISRCTN73545489_ResultsPlainEnglish_09Jan25.docx

Editorial Notes

01/04/2025: Contact details updated.
20/02/2025: Cancer Research UK plain English summary link added.
09/01/2025: Publication reference and plain English results added.
23/07/2024: The intention to publish date was changed from 31/01/2024 to 31/10/2024.
17/07/2023: The publication and dissemination plan was updated. The intention to publish date was changed from 30/09/2023 to 31/01/2024.
17/03/2022: The following changes have been made:
1. The recruitment end date has been changed from 31/03/2022 to 18/02/2022.
2. The overall trial end date has been changed from 31/07/2022 to 18/06/2022 and the plain English summary has been updated to reflect this change.
3. The total final enrolment number has been added.
21/01/2022: The overall end date was changed from 31/05/2022 to 31/07/2022.
19/01/2022: The recruitment end date has been changed from 31/01/2022 to 31/03/2022.
06/08/2021: A contact was removed from the record.
26/07/2021: The following changes have been made:
1. The recruitment end date has been changed from 31/07/2021 to 31/01/2022.
2. The overall trial end date has been changed from 30/11/2021 to 31/05/2022.
3. The intention to publish date has been changed from 31/03/2023 to 30/09/2023.
23/03/2021: The recruitment end date was changed from 31/03/2021 to 31/07/2021.
07/08/2020: The following changes have been made:
1. The recruitment end date has been changed from 31/07/2020 to 31/03/2021.
2. The overall trial end date has been changed from 31/03/2021 to 31/11/2021.
3. The intention to publish date has been changed from 31/03/2022 to 31/03/2023.
01/07/2020: This study has restarted and begun randomization at some sites, however, due to current public health guidance, recruitment for this study is still paused at some participating centres.
04/05/2020: Due to current public health guidance, recruitment for this study has been paused at a number of participating centres.
11/02/2020: The following changes have been made:
1. Publication reference added.
2. The recruitment end date has been changed from 31/03/2020 to 31/07/2020.
20/06/2019: Internal review.
15/01/2019: The following changes were made to the trial record:
1. Australia was added to the countries of recruitment.
2. Contact details updated.
3. National Health Medical and Research Council of Australia was added as a funder.
17/12/2018: IPD sharing statement added.
10/12/2018: The following changes were made to the trial record:
1. Trial website added.
2. Contact details updated.
3. The primary and secondary outcome measures and exclusion criteria were updated.
03/12/2018: The following changes were made to the trial record:
1. The recruitment end date was changed from 30/08/2019 to 31/03/2020.
2. The overall trial end date was changed from 28/02/2020 to 30/11/2021.
3. The target number of participants was changed from 616 in the UK + 200 in Australia to 616 in the UK and Australia together.
4. The EudraCT and ClinicalTrials.gov numbers were added.