Back to resultsTRial to EvaluAte Tranexamic Acid Therapy in Thrombocytopenia (TREATT)
Primary Purpose
Hematologic Neoplasms, Hemorrhage, Hematopoietic Stem Cell Transplantation
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Tranexamic acid (TXA).
Placebo
Sponsored by
About this trial
This is an interventional supportive care trial for Hematologic Neoplasms focused on measuring Tranexamic acid, Platelet transfusion
Eligibility Criteria
Inclusion Criteria:
Patients are eligible for this trial if:
- Aged ≥18 years of age
- Confirmed diagnosis of a haematological malignancy
- Undergoing chemotherapy, or chemotherapy is planned, or haematopoietic stem cell transplantation
- Anticipated to have a hypoproliferative thrombocytopenia resulting in a platelet count of ≤10x10⁹/L for ≥ 5 days
- Able to comply with treatment and monitoring
Exclusion Criteria:
A patient will not be eligible for this trial if he/she fulfils one or more of the following criteria:
- 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.
- Diagnosis of acute promyelocytic leukaemia (APML) and undergoing induction chemotherapy
- Patients with a diagnosis/previous history of veno-occlusive disease (also called sinusoidal obstruction syndrome)
Patients with known inherited or acquired prothrombotic disorders e.g.
- Lupus anticoagulant
- Positive antiphospholipids
- 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
- Patients receiving L-asparaginase as part of their current cycle of treatment
- History of immune thrombocytopenia (ITP), thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome (HUS)
- Patients with overt disseminated intravascular coagulation (DIC) (See Appendix 3 in the protocol for definition)
- Patients requiring a platelet transfusion threshold >10x10/⁹L 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.)
Patients with a known inherited or acquired bleeding disorder e.g.
- Acquired storage pool deficiency
- Paraproteinaemia with platelet inhibition
- Patients receiving anticoagulant therapy or anti-platelet therapy
- Patients with visible haematuria at time of randomisation
- Patients with anuria (defined as urine output < 10 mls/hr over 24 hours).
- Patients with severe renal impairment (eGFR ≤30 ml/min/1.73m²)
- Patients with a previous history of epilepsy, convulsions, fits or seizures
- Patients who are pregnant or breast-feeding
- Allergic to tranexamic acid.
- Patients enrolled in other trials involving platelet transfusions, anti-fibrinolytics, platelet growth factors or other pro-coagulant agents.
- Patients previously randomised into this trial at any stage of their treatment.
Sites / Locations
- Royal Adelaide Hospital
- Royal Brisbane
- Canberra Hospital
- Andrew Love Cancer Centre
- Alfred Hospital
- Monash Health
- St Vincent's Hospital
- Victorian Comprehensive Cancer Centre
- Royal North Shore Hospital
- St Vincent's Hospital
- Westmead Hospital
- Royal United Hospital
- Belfast City Hospital
- Heartlands Hospital
- Queen Elizabeth Hospital
- Bristol Haematology and Oncology Centre
- University Hospital Coventry
- Royal Devon and Exeter Hospital
- Beatson West of Scotland Cancer Centre
- St James's Hospital
- Lincoln County Hospital
- King's College Hospital
- University College London Hospitals
- Freeman Hospital
- Churchill Hospital
- Derriford Hospital
- Salisbury District Hospital
- Royal Hallamshire Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Intervention Arm
Control Arm
Arm Description
Tranexamic acid (TXA). Dose schedule TXA 1g every eight hours IV or 1.5g every eight hours PO.
Placebo (saline) if administration is IV. Placebo tablet matched for appearance to TXA if oral.
Outcomes
Primary Outcome Measures
The proportion of patients who die or have bleeding of WHO grade 2 or above by WHO criteria during the first 30 days from the first dose of trial treatment, or planned first dose for those participants who do not receive treatment.
The proportion of patients who die or have bleeding of WHO grade 2 or above by WHO criteria during the first 30 days from the first dose of trial treatment, or planned first dose for those participants who do not receive treatment.
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
Proportion of days with bleeding (WHO grade 2 or above) up to Study Day 30.
Number of days where WHO grade 2 or above bleeding has been recorded bleeding using WHO bleeding criteria.
Time to first episode of bleeding of WHO grade 2 or greater up to study day 30.
Bleeding assessed using WHO bleeding criteria.
Highest grade of bleeding a patient experiences up to study day 30.
Measured using WHO bleeding criteria.
Number of platelet transfusions per patient up to study day 30.
Measured by number of recorded platelet transfusions per patient.
Number of red cell transfusions per patient up to study day 30.
Measured by number of recorded red cell transfusions per patient.
Proportion of patients surviving at least 30 days without a platelet transfusion.
Measured by calculating number of patients surviving at least 30 days without a platelet transfusion.
Proportion of patients surviving at least 30 days without a red cell transfusion.
Measured by calculating the number of patients surviving at least 30 days without a red cell transfusion.
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.
Measured by calculating number of clinically diagnosed thrombotic events from Treatment Day 1 i.e the first day that the investigational medicinal product (IMP) is administered, up to and including the next 120 days.
Number of patients developing Veno-occlusive Disease (VOD; Sinusoidal obstructive syndrome, SOS) within 60 days of first administration of trial treatment.
Measured by calculating number of patients developing Veno-occlusive Disease (VOD; Sinusoidal obstructive syndrome, SOS) within 60 days of Treatment Day 1 i.e the first day that the IMP is administered.
All-cause mortality during the first 30 days and 120 days after the first dose of trial treatment is administered. All-cause mortality during the first 30 days and 120 days after the first dose of trial treatment is administered
Measured by calculating number of deaths in first 30 days and 120 days after Treatment Day 1 i.e the first day that the IMP is administered.
Death due to thrombosis during the first 120 days after the first dose of trial treatment is administered.
Measured by calculating number of deaths due to thrombosis during the first 120 days after Treatment Day 1 i.e the first day that the IMP is administered.
Death due to bleeding during the first 30 days after the first dose of trial treatment is administered.
Measured by calculating number of deaths due to bleeding during the first 30 days
Number of serious adverse events (SAE) from first administration of trial treatment until 60 days after the first dose of trial treatment is administered.
Measured by calculating the total number of SAE's reported from first administration of IMP.
Full Information
NCT ID
NCT03136445
First Posted
February 21, 2017
Last Updated
June 20, 2022
Sponsor
NHS Blood and Transplant
Collaborators
National Health and Medical Research Council, Australia, Monash University
1. Study Identification
Unique Protocol Identification Number
NCT03136445
Brief Title
TRial to EvaluAte Tranexamic Acid Therapy in Thrombocytopenia
Acronym
TREATT
Official Title
A Double-blind, Randomised Controlled Trial Evaluating the Safety and Efficacy of Antifibrinolytics (Tranexamic Acid) in Patients With Haematological Malignancies With Severe Thrombocytopenia
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
June 2015 (Actual)
Primary Completion Date
February 18, 2022 (Actual)
Study Completion Date
June 18, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NHS Blood and Transplant
Collaborators
National Health and Medical Research Council, Australia, Monash University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
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. The investigators will measure the rates of bleeding daily using a short structured assessment of bleeding and will record the number of transfusions given to patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Neoplasms, Hemorrhage, Hematopoietic Stem Cell Transplantation
Keywords
Tranexamic acid, Platelet transfusion
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
616 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intervention Arm
Arm Type
Experimental
Arm Description
Tranexamic acid (TXA). Dose schedule TXA 1g every eight hours IV or 1.5g every eight hours PO.
Arm Title
Control Arm
Arm Type
Placebo Comparator
Arm Description
Placebo (saline) if administration is IV. Placebo tablet matched for appearance to TXA if oral.
Intervention Type
Drug
Intervention Name(s)
Tranexamic acid (TXA).
Other Intervention Name(s)
Cyklokapron®, trans-4-(aminomethyl)cyclohexanecarboxylic acid, Lysteda
Intervention Description
IV or oral preparation. IV tranexamic acid or Oral tablet of tranexamic acid.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo for tranexamic acid
Intervention Description
IV (saline) or oral placebo tablets
Primary Outcome Measure Information:
Title
The proportion of patients who die or have bleeding of WHO grade 2 or above by WHO criteria during the first 30 days from the first dose of trial treatment, or planned first dose for those participants who do not receive treatment.
Description
The proportion of patients who die or have bleeding of WHO grade 2 or above by WHO criteria during the first 30 days from the first dose of trial treatment, or planned first dose for those participants who do not receive treatment.
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.
Time Frame
The first 30 days from first dose of trial treatment
Secondary Outcome Measure Information:
Title
Proportion of days with bleeding (WHO grade 2 or above) up to Study Day 30.
Description
Number of days where WHO grade 2 or above bleeding has been recorded bleeding using WHO bleeding criteria.
Time Frame
The first 30 days from first dose of trial treatment .
Title
Time to first episode of bleeding of WHO grade 2 or greater up to study day 30.
Description
Bleeding assessed using WHO bleeding criteria.
Time Frame
The first 30 days from first dose of trial treatment.
Title
Highest grade of bleeding a patient experiences up to study day 30.
Description
Measured using WHO bleeding criteria.
Time Frame
The first 30 days from first dose of trial treatment.
Title
Number of platelet transfusions per patient up to study day 30.
Description
Measured by number of recorded platelet transfusions per patient.
Time Frame
The first 30 days from first dose of trial treatment.
Title
Number of red cell transfusions per patient up to study day 30.
Description
Measured by number of recorded red cell transfusions per patient.
Time Frame
The first 30 days from first dose of trial treatment.
Title
Proportion of patients surviving at least 30 days without a platelet transfusion.
Description
Measured by calculating number of patients surviving at least 30 days without a platelet transfusion.
Time Frame
The first 30 days from first dose of trial treatment.
Title
Proportion of patients surviving at least 30 days without a red cell transfusion.
Description
Measured by calculating the number of patients surviving at least 30 days without a red cell transfusion.
Time Frame
The first 30 days from first dose of trial treatment.
Title
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.
Description
Measured by calculating number of clinically diagnosed thrombotic events from Treatment Day 1 i.e the first day that the investigational medicinal product (IMP) is administered, up to and including the next 120 days.
Time Frame
Up to and including 120 days from the first administration of investigational medicinal product (IMP).
Title
Number of patients developing Veno-occlusive Disease (VOD; Sinusoidal obstructive syndrome, SOS) within 60 days of first administration of trial treatment.
Description
Measured by calculating number of patients developing Veno-occlusive Disease (VOD; Sinusoidal obstructive syndrome, SOS) within 60 days of Treatment Day 1 i.e the first day that the IMP is administered.
Time Frame
Up to and including 60 days from the first administration of IMP.
Title
All-cause mortality during the first 30 days and 120 days after the first dose of trial treatment is administered. All-cause mortality during the first 30 days and 120 days after the first dose of trial treatment is administered
Description
Measured by calculating number of deaths in first 30 days and 120 days after Treatment Day 1 i.e the first day that the IMP is administered.
Time Frame
Up to and including 120 days from the first administration of IMP.
Title
Death due to thrombosis during the first 120 days after the first dose of trial treatment is administered.
Description
Measured by calculating number of deaths due to thrombosis during the first 120 days after Treatment Day 1 i.e the first day that the IMP is administered.
Time Frame
Up to and including 120 days from the first administration of IMP.
Title
Death due to bleeding during the first 30 days after the first dose of trial treatment is administered.
Description
Measured by calculating number of deaths due to bleeding during the first 30 days
Time Frame
Up to and including 30 days from the first administration of IMP.
Title
Number of serious adverse events (SAE) from first administration of trial treatment until 60 days after the first dose of trial treatment is administered.
Description
Measured by calculating the total number of SAE's reported from first administration of IMP.
Time Frame
Up to and including 60 days from the first administration of IMP.
Other Pre-specified Outcome Measures:
Title
Proportion of days with thrombocytopenia (≤10x10⁹/L, ≤30x10⁹L, ≤50x10⁹/L).
Description
Measured by number of days that the patient's laboratory results indicate that the patient is thrombocytopenic.
Time Frame
Measured during first 30 days from first dose of IMP.
Title
Reasons for platelet and red cell transfusions.
Description
Reasons for platelet and red cell transfusions as documented by clinician.
Time Frame
Measured during first 30 days from first dose of IMP.
Title
Proportion of days with fever
Description
Highest daily temperature ≥ 38.1°C
Time Frame
Measured during first 30 days from first dose of IMP.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients are eligible for this trial if:
Aged ≥18 years of age
Confirmed diagnosis of a haematological malignancy
Undergoing chemotherapy, or chemotherapy is planned, or haematopoietic stem cell transplantation
Anticipated to have a hypoproliferative thrombocytopenia resulting in a platelet count of ≤10x10⁹/L for ≥ 5 days
Able to comply with treatment and monitoring
Exclusion Criteria:
A patient will not be eligible for this trial if he/she fulfils one or more of the following criteria:
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.
Diagnosis of acute promyelocytic leukaemia (APML) and undergoing induction chemotherapy
Patients with a diagnosis/previous history of veno-occlusive disease (also called sinusoidal obstruction syndrome)
Patients with known inherited or acquired prothrombotic disorders e.g.
Lupus anticoagulant
Positive antiphospholipids
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
Patients receiving L-asparaginase as part of their current cycle of treatment
History of immune thrombocytopenia (ITP), thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome (HUS)
Patients with overt disseminated intravascular coagulation (DIC) (See Appendix 3 in the protocol for definition)
Patients requiring a platelet transfusion threshold >10x10/⁹L 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.)
Patients with a known inherited or acquired bleeding disorder e.g.
Acquired storage pool deficiency
Paraproteinaemia with platelet inhibition
Patients receiving anticoagulant therapy or anti-platelet therapy
Patients with visible haematuria at time of randomisation
Patients with anuria (defined as urine output < 10 mls/hr over 24 hours).
Patients with severe renal impairment (eGFR ≤30 ml/min/1.73m²)
Patients with a previous history of epilepsy, convulsions, fits or seizures
Patients who are pregnant or breast-feeding
Allergic to tranexamic acid.
Patients enrolled in other trials involving platelet transfusions, anti-fibrinolytics, platelet growth factors or other pro-coagulant agents.
Patients previously randomised into this trial at any stage of their treatment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lise J Estcourt, MBBChir MSc DPhil MRCP FRCPath
Organizational Affiliation
NHS Blood and Transplant
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Zoe K McQuilten, MBBS PhD
Organizational Affiliation
Monash University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Simon J Stanworth, DPhil FRCP FRCPath
Organizational Affiliation
NHS Blood and Transplant
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Erica M Wood, MB BS, FRACP, FRCPA
Organizational Affiliation
Monash University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Royal Adelaide Hospital
City
Adelaide
Country
Australia
Facility Name
Royal Brisbane
City
Brisbane
Country
Australia
Facility Name
Canberra Hospital
City
Canberra
Country
Australia
Facility Name
Andrew Love Cancer Centre
City
Geelong
Country
Australia
Facility Name
Alfred Hospital
City
Melbourne
Country
Australia
Facility Name
Monash Health
City
Melbourne
Country
Australia
Facility Name
St Vincent's Hospital
City
Melbourne
Country
Australia
Facility Name
Victorian Comprehensive Cancer Centre
City
Melbourne
Country
Australia
Facility Name
Royal North Shore Hospital
City
St Leonards
Country
Australia
Facility Name
St Vincent's Hospital
City
Sydney
Country
Australia
Facility Name
Westmead Hospital
City
Westmead
Country
Australia
Facility Name
Royal United Hospital
City
Bath
Country
United Kingdom
Facility Name
Belfast City Hospital
City
Belfast
Country
United Kingdom
Facility Name
Heartlands Hospital
City
Birmingham
Country
United Kingdom
Facility Name
Queen Elizabeth Hospital
City
Birmingham
Country
United Kingdom
Facility Name
Bristol Haematology and Oncology Centre
City
Bristol
Country
United Kingdom
Facility Name
University Hospital Coventry
City
Coventry
Country
United Kingdom
Facility Name
Royal Devon and Exeter Hospital
City
Exeter
Country
United Kingdom
Facility Name
Beatson West of Scotland Cancer Centre
City
Glasgow
Country
United Kingdom
Facility Name
St James's Hospital
City
Leeds
Country
United Kingdom
Facility Name
Lincoln County Hospital
City
Lincoln
Country
United Kingdom
Facility Name
King's College Hospital
City
London
Country
United Kingdom
Facility Name
University College London Hospitals
City
London
Country
United Kingdom
Facility Name
Freeman Hospital
City
Newcastle
Country
United Kingdom
Facility Name
Churchill Hospital
City
Oxford
Country
United Kingdom
Facility Name
Derriford Hospital
City
Plymouth
Country
United Kingdom
Facility Name
Salisbury District Hospital
City
Salisbury
Country
United Kingdom
Facility Name
Royal Hallamshire Hospital
City
Sheffield
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing Time Frame
9 months after publication and ending 5 years following article publication.
IPD Sharing Access Criteria
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.
Citations:
PubMed Identifier
31615553
Citation
Estcourt LJ, McQuilten Z, Powter G, Dyer C, Curnow E, Wood EM, Stanworth SJ; TREATT Trial Collaboration (provisional). The TREATT Trial (TRial to EvaluAte Tranexamic acid therapy in Thrombocytopenia): safety and efficacy of tranexamic acid in patients with haematological malignancies with severe thrombocytopenia: study protocol for a double-blind randomised controlled trial. Trials. 2019 Oct 15;20(1):592. doi: 10.1186/s13063-019-3663-2.
Results Reference
derived
Learn more about this trial
TRial to EvaluAte Tranexamic Acid Therapy in Thrombocytopenia
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