Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Hemorrhage
Conditions
Keywords
Tranexamic acid, Platelet transfusion
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.
Interventions
DRUGTranexamic acid (TXA).
IV or oral preparation. IV tranexamic acid or Oral tablet of tranexamic acid.
DRUGPlacebo
IV (saline) or oral placebo tablets
Sponsors
National Health and Medical Research Council, Australia
Monash University
NHS Blood and Transplant
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients are eligible for this trial if: 1. Aged ≥18 years of age 2. Confirmed diagnosis of a haematological malignancy 3. Undergoing chemotherapy, or chemotherapy is planned, or haematopoietic stem cell transplantation 4. Anticipated to have a hypoproliferative thrombocytopenia resulting in a platelet count of ≤10x10⁹/L for ≥ 5 days 5. 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: 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. 1. Lupus anticoagulant 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 disseminated intravascular coagulation (DIC) (See Appendix 3 in the protocol for definition) 9. 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.) 10. Patients with a known inherited or acquired bleeding disorder e.g. 1. Acquired storage pool deficiency 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 breast-feeding 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.
Design outcomes
Primary
| Measure | Time frame | 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. | The first 30 days from first dose of trial 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
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Surviving at Least 30 Days Without a Platelet Transfusion. | The first 30 days from first dose of trial treatment. | Measured by calculating number of patients surviving at least 30 days without a platelet transfusion. |
| All-cause Mortality During the First 30 Days and 120 Days After the First Dose of Trial Treatment is Administered. | Up to and including 120 days from the first administration of IMP. | 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. | Up to and including 120 days from the first administration of IMP. | 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. | Up to and including 30 days from the first administration of IMP. | 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. | Up to and including 60 days from the first administration of IMP. | Measured by calculating the total number of SAE's reported from first administration of IMP. |
| Mean (SD) Percentage of Days With WHO Grade 2 Bleeding or Above, Per Participant. | The first 30 days from first dose of trial treatment . | 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. | The first 30 days from first dose of trial treatment. | Bleeding assessed using WHO bleeding criteria. Time to first episode of bleeding of WHO grade 2 or above was estimated using a cumulative incidence function, with death as a competing risk. The lower quartile for the time is reported as the median was not estimable. |
| Highest Grade of Bleeding a Patient Experiences up to Study Day 30. | The first 30 days from first dose of trial treatment. | Measured using WHO bleeding criteria (The higher the grade, the most severe the bleed). Grade 0: no bleeding Grade 1: petechial bleeding Grade 2: mild blood loss (clinically significant) Grade 3: gross blood loss, requires transfusion(severe) Grade 4: debilitating blood loss, retinal or cerebral associated with fatality |
| Number of Platelet Transfusions Per Patient up to Study Day 30. | The first 30 days from first dose of trial treatment. | Measured by number of recorded platelet transfusions per patient. |
| Number of Red Cell Transfusions Per Patient up to Study Day 30. | The first 30 days from first dose of trial treatment. | Measured by number of recorded red cell transfusions per patient. |
| Proportion of Patients Surviving at Least 30 Days Without a Red Cell Transfusion. | The first 30 days from first dose of trial treatment. | Measured by calculating the number of patients surviving at least 30 days without a red cell transfusion. |
| Number of Participants With a Thrombotic Event From First Administration of Trial Treatment up to and Including 120 Days After the First Dose of Trial Treatment is Received (N) | Up to and including 120 days from the first administration of investigational medicinal product (IMP). | Measured by calculating number of patients developing clinically diagnosed thrombotic events within 120 days of Treatment Day 1 i.e the first day that the IMP is administered. |
| Number of Patients Developing Veno-occlusive Disease (VOD; Sinusoidal Obstructive Syndrome, SOS) Within 60 Days of First Administration of Trial Treatment. | Up to and including 60 days from the first administration of IMP. | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Reasons for Red Cell Transfusions. | Measured during first 30 days from first dose of IMP. | Reasons for red cell transfusions as documented by clinician. |
| Proportion of Days With Fever | Measured during first 30 days from first dose of IMP. | Highest daily temperature ≥ 38.1°C |
| Reasons for Platelet Transfusions. | Measured during first 30 days from first dose of IMP. | Reasons for platelet transfusions as documented by clinician. |
| Proportion of Days With Thrombocytopenia (≤10x10⁹/L, ≤30x10⁹L, ≤50x10⁹/L). | Measured during first 30 days from first dose of IMP. | Measured by number of days that the patient's laboratory results indicate that the patient is thrombocytopenic. |
Countries
Australia, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intervention Arm Tranexamic acid (TXA). Dose schedule TXA 1g every eight hours IV or 1.5g every eight hours PO.
Tranexamic acid (TXA).: IV or oral preparation. IV tranexamic acid or Oral tablet of tranexamic acid. | 310 |
| Control Arm Placebo (saline) if administration is IV. Placebo tablet matched for appearance to TXA if oral.
Placebo: IV (saline) or oral placebo tablets | 306 |
| Total | 616 |
Baseline characteristics
| Characteristic | Control Arm | Total | Intervention Arm |
|---|---|---|---|
| Age, Continuous | 55.3 years STANDARD_DEVIATION 12.1 | 55.6 years STANDARD_DEVIATION 12.2 | 55.8 years STANDARD_DEVIATION 12.3 |
| Diagnosis ALL | 11 Participants | 20 Participants | 9 Participants |
| Diagnosis AML | 129 Participants | 264 Participants | 135 Participants |
| Diagnosis APL | 2 Participants | 2 Participants | 0 Participants |
| Diagnosis CLL | 4 Participants | 7 Participants | 3 Participants |
| Diagnosis CML | 7 Participants | 12 Participants | 5 Participants |
| Diagnosis Hodgkin's Lymphoma | 12 Participants | 29 Participants | 17 Participants |
| Diagnosis MDS | 22 Participants | 40 Participants | 18 Participants |
| Diagnosis Myeloma | 36 Participants | 71 Participants | 35 Participants |
| Diagnosis Non-Hodgkin Lymphoma | 62 Participants | 132 Participants | 70 Participants |
| Diagnosis Other | 21 Participants | 38 Participants | 17 Participants |
| FACT-G subscale score at randomisation Emotional well-being | 18.5 scores on a scale STANDARD_DEVIATION 4.3 | 18.4 scores on a scale STANDARD_DEVIATION 4.2 | 18.3 scores on a scale STANDARD_DEVIATION 4.1 |
| FACT-G subscale score at randomisation Functional well-being | 14.3 scores on a scale STANDARD_DEVIATION 6.8 | 14.3 scores on a scale STANDARD_DEVIATION 6.5 | 14.3 scores on a scale STANDARD_DEVIATION 6.2 |
| FACT-G subscale score at randomisation Physical well-being | 17.1 scores on a scale STANDARD_DEVIATION 6.7 | 16.7 scores on a scale STANDARD_DEVIATION 6.9 | 16.4 scores on a scale STANDARD_DEVIATION 7.1 |
| FACT-G subscale score at randomisation Social/family well-being | 23.7 scores on a scale STANDARD_DEVIATION 4.5 | 23.7 scores on a scale STANDARD_DEVIATION 4.6 | 23.8 scores on a scale STANDARD_DEVIATION 4.7 |
| FACT-G total score at randomisation | 73.6 scores on a scale STANDARD_DEVIATION 16.6 | 73.1 scores on a scale STANDARD_DEVIATION 15.6 | 72.6 scores on a scale STANDARD_DEVIATION 14.5 |
| FACT-Th total score at randomisation | 127.6 scores on a scale STANDARD_DEVIATION 24.5 | 126.7 scores on a scale STANDARD_DEVIATION 23.3 | 125.7 scores on a scale STANDARD_DEVIATION 22 |
| Haemoglobin at consent | 98.5 G/L STANDARD_DEVIATION 18 | 99.4 G/L STANDARD_DEVIATION 18 | 100.2 G/L STANDARD_DEVIATION 18.1 |
| Haemoglobin at randomisation | 91.2 G/L STANDARD_DEVIATION 15.8 | 92.8 G/L STANDARD_DEVIATION 15.9 | 94.3 G/L STANDARD_DEVIATION 16 |
| Height | 171.7 cm STANDARD_DEVIATION 9.7 | 172.1 cm STANDARD_DEVIATION 9.9 | 172.4 cm STANDARD_DEVIATION 10.1 |
| Medical history Confirmed invasive fungal infection | 3 Participants | 13 Participants | 10 Participants |
| Medical history Diabetes requiring treatment | 20 Participants | 41 Participants | 21 Participants |
| Medical history HLA antibodies | 6 Participants | 7 Participants | 1 Participants |
| Medical history Hypertension requiring treatment | 40 Participants | 82 Participants | 42 Participants |
| Medical history Other malignancy | 8 Participants | 18 Participants | 10 Participants |
| Medical history Renal impairment requiring treatment | 5 Participants | 11 Participants | 6 Participants |
| Platelet count at consent | 113.1 10^9 cells/L STANDARD_DEVIATION 94.9 | 114.7 10^9 cells/L STANDARD_DEVIATION 99.1 | 116.2 10^9 cells/L STANDARD_DEVIATION 103.3 |
| Platelet count at randomisation | 29.2 10^9 cells/L STANDARD_DEVIATION 13.3 | 30.4 10^9 cells/L STANDARD_DEVIATION 15.9 | 31.7 10^9 cells/L STANDARD_DEVIATION 18.1 |
| Race/Ethnicity, Customized Aboriginal | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Arab / Other Middle East ancestry | 3 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 14 Participants | 21 Participants | 7 Participants |
| Race/Ethnicity, Customized Black African | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Black Caribbean | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized (Mixed ethnic group:) Other mixed ethnic group | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized (Mixed ethnic group:) White / Black Caribbean | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized (Mixed ethnic group:) White / Other | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 9 Participants | 4 Participants |
| Race/Ethnicity, Customized Unknown / Not Stated | 13 Participants | 30 Participants | 17 Participants |
| Race/Ethnicity, Customized White | 266 Participants | 538 Participants | 272 Participants |
| Sex/Gender, Customized Female | 120 Participants | 235 Participants | 115 Participants |
| Sex/Gender, Customized Male | 186 Participants | 380 Participants | 194 Participants |
| Treatment plan Allograft | 79 Participants | 156 Participants | 77 Participants |
| Treatment plan Autograft | 105 Participants | 216 Participants | 111 Participants |
| Treatment plan Consolidation chemotherapy | 46 Participants | 95 Participants | 49 Participants |
| Treatment plan Induction chemotherapy | 72 Participants | 142 Participants | 70 Participants |
| Treatment plan Other | 4 Participants | 6 Participants | 2 Participants |
| Weight | 80.5 kg STANDARD_DEVIATION 17.6 | 80.8 kg STANDARD_DEVIATION 17.1 | 81.1 kg STANDARD_DEVIATION 16.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 23 / 300 | 14 / 297 |
| other Total, other adverse events | 8 / 300 | 5 / 297 |
| serious Total, serious adverse events | 77 / 300 | 82 / 297 |
Outcome results
Primary
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.
Time frame: The first 30 days from first dose of trial treatment
Population: Participants with primary outcome data reported
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention Arm | 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. | 31.7 percentage of participants |
| Control Arm | 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. | 34.2 percentage of participants |
Secondary
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.
Time frame: Up to and including 120 days from the first administration of IMP.
Population: 4 Participants were missing mortality data and so weren't analysd
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Intervention Arm | All-cause Mortality During the First 30 Days and 120 Days After the First Dose of Trial Treatment is Administered. | 30 days | 2.9 proportion |
| Intervention Arm | All-cause Mortality During the First 30 Days and 120 Days After the First Dose of Trial Treatment is Administered. | 120 days | 8.7 proportion |
| Control Arm | All-cause Mortality During the First 30 Days and 120 Days After the First Dose of Trial Treatment is Administered. | 30 days | 1.1 proportion |
| Control Arm | All-cause Mortality During the First 30 Days and 120 Days After the First Dose of Trial Treatment is Administered. | 120 days | 5.3 proportion |
Secondary
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
Time frame: Up to and including 30 days from the first administration of IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention Arm | Death Due to Bleeding During the First 30 Days After the First Dose of Trial Treatment is Administered. | 0 percent |
| Control Arm | Death Due to Bleeding During the First 30 Days After the First Dose of Trial Treatment is Administered. | 0 percent |
Secondary
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.
Time frame: Up to and including 120 days from the first administration of IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention Arm | Death Due to Thrombosis During the First 120 Days After the First Dose of Trial Treatment is Administered. | 0 percent |
| Control Arm | Death Due to Thrombosis During the First 120 Days After the First Dose of Trial Treatment is Administered. | 0 percent |
Secondary
Highest Grade of Bleeding a Patient Experiences up to Study Day 30.
Measured using WHO bleeding criteria (The higher the grade, the most severe the bleed). Grade 0: no bleeding Grade 1: petechial bleeding Grade 2: mild blood loss (clinically significant) Grade 3: gross blood loss, requires transfusion(severe) Grade 4: debilitating blood loss, retinal or cerebral associated with fatality
Time frame: The first 30 days from first dose of trial treatment.
Population: Data is only presented for participants who experienced at least one bleed
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Intervention Arm | Highest Grade of Bleeding a Patient Experiences up to Study Day 30. | Grade 0 | 7 Participants |
| Intervention Arm | Highest Grade of Bleeding a Patient Experiences up to Study Day 30. | Grade unassigned | 0 Participants |
| Intervention Arm | Highest Grade of Bleeding a Patient Experiences up to Study Day 30. | Grade 2 | 85 Participants |
| Intervention Arm | Highest Grade of Bleeding a Patient Experiences up to Study Day 30. | Grade 3 | 0 Participants |
| Intervention Arm | Highest Grade of Bleeding a Patient Experiences up to Study Day 30. | Grade 4 | 2 Participants |
| Intervention Arm | Highest Grade of Bleeding a Patient Experiences up to Study Day 30. | Grade 1 | 111 Participants |
| Control Arm | Highest Grade of Bleeding a Patient Experiences up to Study Day 30. | Grade 4 | 1 Participants |
| Control Arm | Highest Grade of Bleeding a Patient Experiences up to Study Day 30. | Grade 0 | 6 Participants |
| Control Arm | Highest Grade of Bleeding a Patient Experiences up to Study Day 30. | Grade 3 | 3 Participants |
| Control Arm | Highest Grade of Bleeding a Patient Experiences up to Study Day 30. | Grade unassigned | 1 Participants |
| Control Arm | Highest Grade of Bleeding a Patient Experiences up to Study Day 30. | Grade 1 | 121 Participants |
| Control Arm | Highest Grade of Bleeding a Patient Experiences up to Study Day 30. | Grade 2 | 93 Participants |
Secondary
Mean (SD) Percentage of Days With WHO Grade 2 Bleeding or Above, Per Participant.
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 .
Population: Participants with primary outcome data reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Arm | Mean (SD) Percentage of Days With WHO Grade 2 Bleeding or Above, Per Participant. | 3.1 percentage of days | Standard Deviation 9.5 |
| Control Arm | Mean (SD) Percentage of Days With WHO Grade 2 Bleeding or Above, Per Participant. | 3.2 percentage of days | Standard Deviation 7.8 |
Secondary
Number of Participants With a Thrombotic Event From First Administration of Trial Treatment up to and Including 120 Days After the First Dose of Trial Treatment is Received (N)
Measured by calculating number of patients developing clinically diagnosed thrombotic events within 120 days of 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 investigational medicinal product (IMP).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Arm | Number of Participants With a Thrombotic Event From First Administration of Trial Treatment up to and Including 120 Days After the First Dose of Trial Treatment is Received (N) | 8 Participants |
| Control Arm | Number of Participants With a Thrombotic Event From First Administration of Trial Treatment up to and Including 120 Days After the First Dose of Trial Treatment is Received (N) | 5 Participants |
Secondary
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.
Time frame: Up to and including 60 days from the first administration of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Arm | Number of Patients Developing Veno-occlusive Disease (VOD; Sinusoidal Obstructive Syndrome, SOS) Within 60 Days of First Administration of Trial Treatment. | 3 Participants |
| Control Arm | Number of Patients Developing Veno-occlusive Disease (VOD; Sinusoidal Obstructive Syndrome, SOS) Within 60 Days of First Administration of Trial Treatment. | 2 Participants |
Secondary
Number of Platelet Transfusions Per Patient up to Study Day 30.
Measured by number of recorded platelet transfusions per patient.
Time frame: The first 30 days from first dose of trial treatment.
Population: Participants with primary outcome data reported
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intervention Arm | Number of Platelet Transfusions Per Patient up to Study Day 30. | 3 platelet units |
| Control Arm | Number of Platelet Transfusions Per Patient up to Study Day 30. | 3 platelet units |
Secondary
Number of Red Cell Transfusions Per Patient up to Study Day 30.
Measured by number of recorded red cell transfusions per patient.
Time frame: The first 30 days from first dose of trial treatment.
Population: Participants with primary outcome data reported
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intervention Arm | Number of Red Cell Transfusions Per Patient up to Study Day 30. | 2 Red cell units |
| Control Arm | Number of Red Cell Transfusions Per Patient up to Study Day 30. | 2 Red cell units |
Secondary
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.
Time frame: Up to and including 60 days from the first administration of IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Intervention Arm | Number of Serious Adverse Events (SAE) From First Administration of Trial Treatment Until 60 Days After the First Dose of Trial Treatment is Administered. | Transfusion reaction | 2 Serious adverse events |
| Intervention Arm | Number of Serious Adverse Events (SAE) From First Administration of Trial Treatment Until 60 Days After the First Dose of Trial Treatment is Administered. | Sepsis | 25 Serious adverse events |
| Intervention Arm | Number of Serious Adverse Events (SAE) From First Administration of Trial Treatment Until 60 Days After the First Dose of Trial Treatment is Administered. | Other SAEs | 34 Serious adverse events |
| Intervention Arm | Number of Serious Adverse Events (SAE) From First Administration of Trial Treatment Until 60 Days After the First Dose of Trial Treatment is Administered. | Organ failure | 4 Serious adverse events |
| Intervention Arm | Number of Serious Adverse Events (SAE) From First Administration of Trial Treatment Until 60 Days After the First Dose of Trial Treatment is Administered. | Fever | 24 Serious adverse events |
| Intervention Arm | Number of Serious Adverse Events (SAE) From First Administration of Trial Treatment Until 60 Days After the First Dose of Trial Treatment is Administered. | GvHD | 5 Serious adverse events |
| Intervention Arm | Number of Serious Adverse Events (SAE) From First Administration of Trial Treatment Until 60 Days After the First Dose of Trial Treatment is Administered. | Total number of serious adverse events (SAE) up to day 60 | 94 Serious adverse events |
| Control Arm | Number of Serious Adverse Events (SAE) From First Administration of Trial Treatment Until 60 Days After the First Dose of Trial Treatment is Administered. | GvHD | 7 Serious adverse events |
| Control Arm | Number of Serious Adverse Events (SAE) From First Administration of Trial Treatment Until 60 Days After the First Dose of Trial Treatment is Administered. | Transfusion reaction | 4 Serious adverse events |
| Control Arm | Number of Serious Adverse Events (SAE) From First Administration of Trial Treatment Until 60 Days After the First Dose of Trial Treatment is Administered. | Fever | 20 Serious adverse events |
| Control Arm | Number of Serious Adverse Events (SAE) From First Administration of Trial Treatment Until 60 Days After the First Dose of Trial Treatment is Administered. | Other SAEs | 38 Serious adverse events |
| Control Arm | Number of Serious Adverse Events (SAE) From First Administration of Trial Treatment Until 60 Days After the First Dose of Trial Treatment is Administered. | Total number of serious adverse events (SAE) up to day 60 | 103 Serious adverse events |
| Control Arm | Number of Serious Adverse Events (SAE) From First Administration of Trial Treatment Until 60 Days After the First Dose of Trial Treatment is Administered. | Sepsis | 27 Serious adverse events |
| Control Arm | Number of Serious Adverse Events (SAE) From First Administration of Trial Treatment Until 60 Days After the First Dose of Trial Treatment is Administered. | Organ failure | 7 Serious adverse events |
Secondary
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.
Time frame: The first 30 days from first dose of trial treatment.
Population: Participants with primary outcome data reported
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention Arm | Proportion of Patients Surviving at Least 30 Days Without a Platelet Transfusion. | 8.3 proportion |
| Control Arm | Proportion of Patients Surviving at Least 30 Days Without a Platelet Transfusion. | 6.4 proportion |
Secondary
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.
Time frame: The first 30 days from first dose of trial treatment.
Population: Participants with primary outcome data reported
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention Arm | Proportion of Patients Surviving at Least 30 Days Without a Red Cell Transfusion. | 29.4 proportion |
| Control Arm | Proportion of Patients Surviving at Least 30 Days Without a Red Cell Transfusion. | 20.5 proportion |
Secondary
Time to First Episode of Bleeding of WHO Grade 2 or Greater up to Study Day 30.
Bleeding assessed using WHO bleeding criteria. Time to first episode of bleeding of WHO grade 2 or above was estimated using a cumulative incidence function, with death as a competing risk. The lower quartile for the time is reported as the median was not estimable.
Time frame: The first 30 days from first dose of trial treatment.
Population: Participants with primary outcome data reported
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intervention Arm | Time to First Episode of Bleeding of WHO Grade 2 or Greater up to Study Day 30. | NA Lower quartile for number of days |
| Control Arm | Time to First Episode of Bleeding of WHO Grade 2 or Greater up to Study Day 30. | NA Lower quartile for number of days |
Other Pre-specified
Proportion of Days With Fever
Highest daily temperature ≥ 38.1°C
Time frame: Measured during first 30 days from first dose of IMP.
Population: Participants with fever data reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Arm | Proportion of Days With Fever | 20 Days | Standard Deviation 21.5 |
| Control Arm | Proportion of Days With Fever | 17.7 Days | Standard Deviation 20.2 |
Other Pre-specified
Proportion of Days With Thrombocytopenia (≤10x10⁹/L, ≤30x10⁹L, ≤50x10⁹/L).
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.
Population: Days platelet count count was recorded (so risk of thrombocytopenia could be detected)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention Arm | Proportion of Days With Thrombocytopenia (≤10x10⁹/L, ≤30x10⁹L, ≤50x10⁹/L). | Thrombocytopenia (≤10x109/L) | 13.7 Days with thrombocytopenia | Standard Deviation 13.9 |
| Intervention Arm | Proportion of Days With Thrombocytopenia (≤10x10⁹/L, ≤30x10⁹L, ≤50x10⁹/L). | Thrombocytopenia (≤30x109/L) | 64.8 Days with thrombocytopenia | Standard Deviation 25.9 |
| Intervention Arm | Proportion of Days With Thrombocytopenia (≤10x10⁹/L, ≤30x10⁹L, ≤50x10⁹/L). | Thrombocytopenia (≤50x109/L) | 78.2 Days with thrombocytopenia | Standard Deviation 22.3 |
| Control Arm | Proportion of Days With Thrombocytopenia (≤10x10⁹/L, ≤30x10⁹L, ≤50x10⁹/L). | Thrombocytopenia (≤10x109/L) | 15.3 Days with thrombocytopenia | Standard Deviation 15.4 |
| Control Arm | Proportion of Days With Thrombocytopenia (≤10x10⁹/L, ≤30x10⁹L, ≤50x10⁹/L). | Thrombocytopenia (≤30x109/L) | 60.2 Days with thrombocytopenia | Standard Deviation 24.8 |
| Control Arm | Proportion of Days With Thrombocytopenia (≤10x10⁹/L, ≤30x10⁹L, ≤50x10⁹/L). | Thrombocytopenia (≤50x109/L) | 74 Days with thrombocytopenia | Standard Deviation 23.1 |
Other Pre-specified
Reasons for Platelet Transfusions.
Reasons for platelet transfusions as documented by clinician.
Time frame: Measured during first 30 days from first dose of IMP.
Population: Participants with at least one platelet transfusion
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Intervention Arm | Reasons for Platelet Transfusions. | Invasive procedure | 27 Platelet transfusions |
| Intervention Arm | Reasons for Platelet Transfusions. | Active bleeding | 59 Platelet transfusions |
| Intervention Arm | Reasons for Platelet Transfusions. | Prophylaxis for platelet count ≤10x109/L | 438 Platelet transfusions |
| Intervention Arm | Reasons for Platelet Transfusions. | Missing data for reasons for platelet transfusions | 10 Platelet transfusions |
| Intervention Arm | Reasons for Platelet Transfusions. | Prophylaxis and platelet count >10x109/L | 671 Platelet transfusions |
| Control Arm | Reasons for Platelet Transfusions. | Missing data for reasons for platelet transfusions | 6 Platelet transfusions |
| Control Arm | Reasons for Platelet Transfusions. | Prophylaxis and platelet count >10x109/L | 705 Platelet transfusions |
| Control Arm | Reasons for Platelet Transfusions. | Invasive procedure | 31 Platelet transfusions |
| Control Arm | Reasons for Platelet Transfusions. | Prophylaxis for platelet count ≤10x109/L | 456 Platelet transfusions |
| Control Arm | Reasons for Platelet Transfusions. | Active bleeding | 66 Platelet transfusions |
Other Pre-specified
Reasons for Red Cell Transfusions.
Reasons for red cell transfusions as documented by clinician.
Time frame: Measured during first 30 days from first dose of IMP.
Population: Participants with at least one red cell transfusion
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Intervention Arm | Reasons for Red Cell Transfusions. | Missing data for reasons for red cell transfusions | 6 Red cell transfusions |
| Intervention Arm | Reasons for Red Cell Transfusions. | Low haemoglobin | 736 Red cell transfusions |
| Intervention Arm | Reasons for Red Cell Transfusions. | Active bleeding | 7 Red cell transfusions |
| Intervention Arm | Reasons for Red Cell Transfusions. | Other | 17 Red cell transfusions |
| Control Arm | Reasons for Red Cell Transfusions. | Other | 14 Red cell transfusions |
| Control Arm | Reasons for Red Cell Transfusions. | Missing data for reasons for red cell transfusions | 6 Red cell transfusions |
| Control Arm | Reasons for Red Cell Transfusions. | Active bleeding | 7 Red cell transfusions |
| Control Arm | Reasons for Red Cell Transfusions. | Low haemoglobin | 818 Red cell transfusions |