Thrombocytopenia
Conditions
Keywords
Thrombocytopenia, Tranexamic Acid, TXA, Chemotherapy induced thrombocytopenia
Brief summary
The purpose of this study is to evaluate the usefulness of antifibrinolytic therapy with tranexamic acid (TXA) in preventing bleeding in patients who are thrombocytopenic due to primary bone marrow disorders or chemotherapy, immunotherapy and/or radiation therapy.
Detailed description
The purpose of this study is to conduct a prospective, randomized, blinded, placebo controlled trial to evaluate the usefulness of antifibrinolytic therapy with tranexamic acid in preventing bleeding in patients who are thrombocytopenic due to primary bone marrow disorders or chemotherapy, immunotherapy and/or radiation therapy. The results of this study will change practice by providing evidence as to whether or not TXA is effective and safe treatment when used as an adjunct to platelet transfusion therapy in the thrombocytopenic patient.
Interventions
DRUGTranexamic Acid
Doses will be given intravenous (IV) or orally (PO) per the discretion of the treating investigator. Doses are administered every 8 hours. When given IV, TXA 1.0 gram will be administered. When given PO, TXA 1.3 grams will be administered
DRUGPlacebo
Doses will be given intravenous (IV) or orally (PO) per the discretion of the treating investigator. Doses are administered every 8 hours. When given IV, Normal Saline will be administered. When given PO, placebo pills will be administered
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(all must be met): * Must be ≥ 18 years of age * Confirmed diagnosis of a hematologic malignancy or aplasia * Undergoing or planned chemotherapy, immunotherapy, or hematopoietic stem cell transplantation * Anticipated to have hypoproliferative thrombocytopenia resulting in a platelet count of ≤ 10,000/microliters for ≥ 5 days * Able to provide informed consent and comply with treatment and monitoring, or having a Legally Authorized Representative (LAR)
Exclusion criteria
(none can be present): * Diagnosis of acute promyelocytic leukemia undergoing induction chemotherapy * History of ITP, TTP or HUS * Subjects receiving L-asparaginase as part of their current cycle of treatment * Subjects with a past history or current diagnosis of arterial or venous thromboembolic disease including acute coronary syndrome, peripheral vascular disease and retinal arterial or venous thrombosis (except when a prior history of central line thrombosis has resolved) * Subjects with a diagnosis/previous history of sinusoidal obstruction syndrome (also called veno-occlusive disease) * Subjects receiving any pro-coagulant agents (e.g. DDAVP, recombinant Factor VIIa or Prothrombin Complex Concentrates (PCC) and/or an antifibrinolytic agent within 48 hours of enrollment, or with known hypercoagulable state * Known inherited or acquired bleeding disorder including, but not limited to: * Acquired storage pool deficiency * Paraproteinemia with platelet inhibition * Known inherited or acquired prothrombotic disorders, including antiphospholipid syndrome. Those with lupus anticoagulant or positive antiphospholipid serology without thrombosis are not excluded. * Subjects receiving anticoagulant therapy or anti-platelet therapy (except when receiving prophylactic anticoagulant or low dose aspirin therapy for prophylaxis only with a plan to discontinue when the platelet count falls below 50,000) * Patients with DIC according to the patient's physician * Subjects with WHO Grade 2 bleeding or greater within 48 hours prior to activation * Subjects requiring a platelet transfusion threshold \> 10,000/microliters at time of randomization * Subjects with anuria (defined as urine output \< 10mls/hr over 24 hours) * Subjects on dialysis * Subjects with creatinine ≥5.7mg/dL * Subjects who are pregnant or nursing or unwilling to use contraception during and for 30 days after taking the study drug (both males and females) * Subjects enrolled in other trials involving platelet transfusions, anti-fibrinolytics, platelet growth factors or other pro-coagulant agents. * Known allergy to tranexamic acid * Having been previously randomized in this study at any stage of their treatment * Subjects who are unwilling to accept blood or blood component transfusions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bleeding Within 30 Days | 30 days after activation of study drug | Proportion of patients with bleeding of WHO grade 2 or above, over the study period of 30 days after activation of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Platelet Transfusions | 30 days after activation of study drug | Number of platelet transfusions per patient during the first 30 days post prescription activation of study drug |
| Number of Days Alive and Without WHO Grade 2 Bleeding | during the first 30 days post activation of study drug | Number of days alive and without WHO grade 2 bleeding or greater during the first 30 days post activation of study drug |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tranexamic Acid (TXA) IV or PO administered after meeting inclusion/exclusion criteria
Tranexamic Acid: Doses will be given intravenous (IV) or orally (PO) per the discretion of the treating investigator. Doses are administered every 8 hours. When given IV, TXA 1.0 gram will be administered. When given PO, TXA 1.3 grams will be administered | 165 |
| Placebo IV Normal Saline or PO placebo pills administered after meeting inclusion/exclusion criteria
Placebo: Doses will be given intravenous (IV) or orally (PO) per the discretion of the treating investigator. Doses are administered every 8 hours. When given IV, Normal Saline will be administered. When given PO, placebo pills will be administered | 165 |
| Total | 330 |
Baseline characteristics
| Characteristic | Placebo | Total | Tranexamic Acid (TXA) |
|---|---|---|---|
| Age, Continuous | 54.3 years STANDARD_DEVIATION 13.2 | 54.2 years STANDARD_DEVIATION 13.1 | 54.1 years STANDARD_DEVIATION 13 |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 12 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 23 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 6 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 8 Participants | 5 Participants |
| Race (NIH/OMB) White | 129 Participants | 270 Participants | 141 Participants |
| Sex: Female, Male Female | 65 Participants | 138 Participants | 73 Participants |
| Sex: Female, Male Male | 100 Participants | 192 Participants | 92 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 19 / 163 | 19 / 163 |
| other Total, other adverse events | 161 / 163 | 161 / 163 |
| serious Total, serious adverse events | 123 / 163 | 110 / 163 |
Outcome results
Primary
Bleeding Within 30 Days
Proportion of patients with bleeding of WHO grade 2 or above, over the study period of 30 days after activation of study drug.
Time frame: 30 days after activation of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tranexamic Acid (TXA) | Bleeding Within 30 Days | 73 Participants |
| Placebo | Bleeding Within 30 Days | 78 Participants |
Secondary
Number of Days Alive and Without WHO Grade 2 Bleeding
Number of days alive and without WHO grade 2 bleeding or greater during the first 30 days post activation of study drug
Time frame: during the first 30 days post activation of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tranexamic Acid (TXA) | Number of Days Alive and Without WHO Grade 2 Bleeding | 28.1 days | Standard Deviation 3.7 |
| Placebo | Number of Days Alive and Without WHO Grade 2 Bleeding | 27.7 days | Standard Deviation 4.7 |
Secondary
Number of Platelet Transfusions
Number of platelet transfusions per patient during the first 30 days post prescription activation of study drug
Time frame: 30 days after activation of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tranexamic Acid (TXA) | Number of Platelet Transfusions | 7.7 platelet transfusions | Standard Deviation 8.7 |
| Placebo | Number of Platelet Transfusions | 7.6 platelet transfusions | Standard Deviation 10.1 |