Coagulation Defect; Acquired, Hemostatic Disorder, Pediatric Cancer, Thrombocytopenia
Conditions
Keywords
tranexamic acid, anti-fibrinolytic agents, chemotherapy-induced thrombocytopenia
Brief summary
This study evaluates the use of tranexamic acid (TXA) in addition to standard therapy in children receiving chemotherapy or blood and/or marrow transplantation to decrease the risk of bleeding. Half of participants will receive tranexamic acid and half of participants will receive placebo.
Detailed description
The purpose of this study is to conduct a prospective, randomized, blinded, placebo controlled trial to evaluate the safety and feasibility of the addition of antifibrinolytic therapy with tranexamic acid to the standard care in patients who are thrombocytopenic due to primary bone marrow disorders or chemotherapy, immunotherapy and/or radiation therapy in order to prevent bleeding. 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
IV medication administered after patient meets inclusion/exclusion criteria
DRUGNormal saline
IV medication administered after patient meets inclusion/exclusion criteria
Sponsors
Meghan McCormick
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The investigational pharmacy will be notified when patients enroll on trial. When participants meet criteria for randomization, this will be completed by the Investigational Pharmacy. The pharmacy will prepare and distribute to floor nursing staff all doses of tranexamic acid (available in IV form as a colorless liquid) or placebo (as an equal volume of normal saline). Labels will not carry identifiers of which study arm the enrolled patient is on.
Intervention model description
This trial is designed as a prospective, randomized, controlled, blinded (patient, caregiver, physician, assessor) trial with two parallel groups and a primary endpoint of feasibility and safety. Randomization will be performed as block randomization with a 1:1 allocation within blocks of size four.
Eligibility
Sex/Gender
ALL
Age
2 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have a confirmed diagnosis of hematologic malignancy or solid tumor malignancy * Patients must be undergoing or planned chemotherapy or BMT * Patients will only be eligible to receive study drug or placebo during inpatient periods * Patients must be predicted to have thrombocytopenia ≤20,000/microliter (uL) for ≥5 days * Patient must have a platelet transfusion threshold of ≤30,000/uL * Patients must be \>14 days beyond their last dose of Pegylated(PEG)-Asparaginase or \>72 hours beyond their last dose of Erwinia Asparaginase * Patients must be able to comply with treatment and monitoring
Exclusion criteria
* Diagnosis of acute promyelocytic leukemia (APL) * History of Immune Thrombocytopenic Purpura (ITP), Thrombotic Thrombocytopenic Purpura (TTP) or Hemolytic Uremic Syndrome (HUS) * Diagnosis of Disseminated Intravascular Coagulopathy (DIC) * History of inherited or acquired bleeding disorder AND/OR inherited or acquired prothrombotic disorder * Patient must not have WHO Grade 2 bleeding or greater within 48 hours prior to enrollment or study drug activation * Patient must not have received PEG-Asparaginase within the 7 day period prior to enrollment. If given within the 8-14 day period prior to enrollment patients are eligible if prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR) and fibrinogen are obtained and are within 1.5 times the upper limits of normal. * Patient must not be receiving tranexamic acid or other anti-fibrinolytic agent or any other agent to promote hemostasis (which includes DDAVP, recombinant Factor VII, Prothrombin Complex Concentrate, Estrogen Derivatives and Progestins) * Patient must not be receiving therapy with anticoagulation or antiplatelet therapy (which includes heparin infusion, enoxaparin, aspirin. If anticoagulant/antiplatelet therapy is discontinued when platelet count is \<50,000/uL patient will be eligible for enrollment) * Patient must not be receiving platelet growth factors * Current thromboembolic event * History of thromboembolic event \<6 months prior to enrollment * Current/prior history of sinusoidal obstruction disease * Visible hematuria * Renal dysfunction (as defined by age-specific creatinine values calculated by Schwartz equation) or hemodialysis or anuria (defined as \<10 mL urine/hour over 24 hours) * History of seizures * Allergy to tranexamic acid * Pregnancy * Unwilling to accept blood product transfusions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug | Adverse Events and Serious Adverse Events (SAE) will be collected on subjects throughout their participation in the study and up to 30 days following discontinuation of the study drug, regardless of attribution. Adverse events and serious adverse events will be tabulated by type and grade according to the NCI CTCAE v 4.03. The hypothesis is that tranexamic acid can be safely added to standard care regimens in patients with hematologic malignancies or solid tumors during periods of severe thrombocytopenia. Analysis limited to a descriptive assessment of the safety of tranexamic acid in patients with hematologic malignancies or solid tumors by reported adverse events, serious adverse events and death. |
| Feasibility of Tranexamic Acid as an Adjunct to Standard Therapy: Number of Participants Eligible and Recruited | From time of recruitment of the first patient until the last patient is enrolled, up to 16 months in duration | Number of participants eligible for study enrollment and recruited. The hypothesis is that tranexamic acid can be safely added to standard care regimens in patients with hematologic malignancies or solid tumors during periods of severe thrombocytopenia. A descriptive assessment of feasibility of recruitment by monitoring number of patients screened, number of patients eligible for enrollment and rate of recruitment (both start-up and ongoing) during study period to be completed by collecting data on the number of patients screened, the number of patients eligible for study inclusion, the number of eligible patients who consent to study inclusion and the number of consented patients activated to the study drug, organized in visual form by CONSORT diagram. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Days Alive and Without WHO Grade 2 Bleeding or Greater | 30 days after 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. Bleeding graded on a scale ranging from 1 (minor bleeding) through 4 (bleeding that is fatal or life-threatening). |
| The Occurrence of Thromboembolic Adverse Events and Serious Adverse Events | From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug | Any venous or arterial thrombosis on standard diagnostic imaging post-randomization |
| World Health Organization (WHO) Bleeding Scale Grade 2 or Higher Bleeding | 30 days after activation of study drug | Proportion of patients with bleeding of WHO grade 2 or above, after activation of study drug. Bleeding graded on a scale ranging from 1 (minor bleeding) through 4 (bleeding that is fatal or life-threatening). |
| Highest Observed Grade of Bleeding (as Measured on WHO Bleeding Scale) During the Study Period | From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug | Highest grade of bleeding (as measured on WHO bleeding scale) during study period in each enrolled patient. Bleeding graded on a scale ranging from 1 (minor bleeding) through 4 (bleeding that is fatal or life-threatening). |
| Bleeding of Any Grade | From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug | Proportion of patients with bleeding of any grade as assessed by WHO bleeding score, after activation of study drug |
| Number of Platelet and Red Blood Cell Transfusions | 30 days after activation of study drug | Number of platelet and red blood cell transfusions per patient during the first 30 days post prescription activation of study drug |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tranexamic Acid Doses will be given intravenous (IV). Doses are administered every 8 hours or three times daily (TID) per the discretion of the treating investigator. TXA dose will be 10mg/kg, diluted in normal saline to a total volume of 15 milliliters (mL).
Tranexamic Acid: IV medication administered after patient meets inclusion/exclusion criteria | 6 |
| Placebo Doses will be given intravenous (IV). Doses are administered every 8 hours or TID per the discretion of the treating investigator. Normal saline will be administered at a total volume of 15mL.
Normal saline: IV medication administered after patient meets inclusion/exclusion criteria | 5 |
| Total | 11 |
Baseline characteristics
| Characteristic | Total | Placebo | Tranexamic Acid |
|---|---|---|---|
| Age, Continuous | 11 years | 11 years | 9.5 years |
| Diagnosis Lymphoid Leukemia | 4 Participants | 0 Participants | 4 Participants |
| Diagnosis Lymphoma | 2 Participants | 1 Participants | 1 Participants |
| Diagnosis Myeloid Leukemia | 2 Participants | 2 Participants | 0 Participants |
| Diagnosis Solid Tumor | 3 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 5 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 8 Participants | 4 Participants | 4 Participants |
| Type of Therapy Allogeneic Hematopoietic Stem Cell Transplant | 2 Participants | 1 Participants | 1 Participants |
| Type of Therapy Autologous Hematopoietic Stem Cell Transplant | 3 Participants | 2 Participants | 1 Participants |
| Type of Therapy Chemotherapy | 6 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 5 |
| other Total, other adverse events | 6 / 6 | 5 / 5 |
| serious Total, serious adverse events | 6 / 6 | 5 / 5 |
Outcome results
Primary
Feasibility of Tranexamic Acid as an Adjunct to Standard Therapy: Number of Participants Eligible and Recruited
Number of participants eligible for study enrollment and recruited. The hypothesis is that tranexamic acid can be safely added to standard care regimens in patients with hematologic malignancies or solid tumors during periods of severe thrombocytopenia. A descriptive assessment of feasibility of recruitment by monitoring number of patients screened, number of patients eligible for enrollment and rate of recruitment (both start-up and ongoing) during study period to be completed by collecting data on the number of patients screened, the number of patients eligible for study inclusion, the number of eligible patients who consent to study inclusion and the number of consented patients activated to the study drug, organized in visual form by CONSORT diagram.
Time frame: From time of recruitment of the first patient until the last patient is enrolled, up to 16 months in duration
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tranexamic Acid | Feasibility of Tranexamic Acid as an Adjunct to Standard Therapy: Number of Participants Eligible and Recruited | Assessed for Eligibility | 693 Participants |
| Tranexamic Acid | Feasibility of Tranexamic Acid as an Adjunct to Standard Therapy: Number of Participants Eligible and Recruited | Screened for Complete Inclusion/Exclusion Criteria | 148 Participants |
| Tranexamic Acid | Feasibility of Tranexamic Acid as an Adjunct to Standard Therapy: Number of Participants Eligible and Recruited | Eligible for Enrollment | 31 Participants |
| Tranexamic Acid | Feasibility of Tranexamic Acid as an Adjunct to Standard Therapy: Number of Participants Eligible and Recruited | Consented to Participate | 11 Participants |
Primary
Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03
Adverse Events and Serious Adverse Events (SAE) will be collected on subjects throughout their participation in the study and up to 30 days following discontinuation of the study drug, regardless of attribution. Adverse events and serious adverse events will be tabulated by type and grade according to the NCI CTCAE v 4.03. The hypothesis is that tranexamic acid can be safely added to standard care regimens in patients with hematologic malignancies or solid tumors during periods of severe thrombocytopenia. Analysis limited to a descriptive assessment of the safety of tranexamic acid in patients with hematologic malignancies or solid tumors by reported adverse events, serious adverse events and death.
Time frame: From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Hypotension | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Blood Bilirubin Increased | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Anemia | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Anorexia | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Bone Pain | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Catheter Related Infection | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Vomiting | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Febrile Neutropenia | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Fever | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Hypoalbuminemia | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Hypotension | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Hypoxia | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Hypophosphatemia | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Rash Maculo-Papular | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Nausea | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Mucositis Oral | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Sinusitis | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Skin Infection | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : White Blood Cell Decreases | 6 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Platelet Count Decreased | 6 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Blood Bilirubin Increased | 1 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Anemia | 4 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Anorexia | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Bone Pain | 1 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Catheter Related Infection | 3 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Vomiting | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Febrile Neutropenia | 2 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Fever | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Hypoalbuminemia | 1 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Nausea | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Hypoxia | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Hypophosphatemia | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Rash Maculo-Papular | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Mucositis Oral | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Sinusitis | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Skin Infection | 1 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : White Blood Cell Decreases | 0 Participants |
| Tranexamic Acid | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Platelet Count Decreased | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Platelet Count Decreased | 5 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Blood Bilirubin Increased | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Hypotension | 1 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Blood Bilirubin Increased | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Anemia | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Platelet Count Decreased | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Anorexia | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Anemia | 4 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Bone Pain | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Hypoxia | 1 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Catheter Related Infection | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Anorexia | 2 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Vomiting | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Sinusitis | 1 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Febrile Neutropenia | 1 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Bone Pain | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Fever | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Hypophosphatemia | 1 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Hypoalbuminemia | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Catheter Related Infection | 1 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Hypotension | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : White Blood Cell Decreases | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Hypoxia | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Vomiting | 2 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Hypophosphatemia | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Rash Maculo-Papular | 2 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Rash Maculo-Papular | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Febrile Neutropenia | 3 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Nausea | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Nausea | 1 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Mucositis Oral | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Fever | 1 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Sinusitis | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Skin Infection | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : Skin Infection | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Hypoalbuminemia | 0 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 4 Adverse Events : White Blood Cell Decreases | 5 Participants |
| Placebo | Safety and Tolerability of Tranexamic Acid in Participants as the Number of Patients With Any Adverse Events and Serious Adverse Events (SAE) as Assessed by CTCAE v4.03 | Grade 3 Adverse Events : Mucositis Oral | 1 Participants |
Secondary
Bleeding of Any Grade
Proportion of patients with bleeding of any grade as assessed by WHO bleeding score, after activation of study drug
Time frame: From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tranexamic Acid | Bleeding of Any Grade | 4 Participants |
| Placebo | Bleeding of Any Grade | 5 Participants |
Secondary
Highest Observed Grade of Bleeding (as Measured on WHO Bleeding Scale) During the Study Period
Highest grade of bleeding (as measured on WHO bleeding scale) during study period in each enrolled patient. Bleeding graded on a scale ranging from 1 (minor bleeding) through 4 (bleeding that is fatal or life-threatening).
Time frame: From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tranexamic Acid | Highest Observed Grade of Bleeding (as Measured on WHO Bleeding Scale) During the Study Period | Grade 5 Bleeding | 0 Participants |
| Tranexamic Acid | Highest Observed Grade of Bleeding (as Measured on WHO Bleeding Scale) During the Study Period | Grade 1 Bleeding | 4 Participants |
| Tranexamic Acid | Highest Observed Grade of Bleeding (as Measured on WHO Bleeding Scale) During the Study Period | Grade 2 Bleeding | 0 Participants |
| Tranexamic Acid | Highest Observed Grade of Bleeding (as Measured on WHO Bleeding Scale) During the Study Period | Grade 3 Bleeding | 0 Participants |
| Tranexamic Acid | Highest Observed Grade of Bleeding (as Measured on WHO Bleeding Scale) During the Study Period | Grade 4 Bleeding | 0 Participants |
| Placebo | Highest Observed Grade of Bleeding (as Measured on WHO Bleeding Scale) During the Study Period | Grade 4 Bleeding | 0 Participants |
| Placebo | Highest Observed Grade of Bleeding (as Measured on WHO Bleeding Scale) During the Study Period | Grade 3 Bleeding | 0 Participants |
| Placebo | Highest Observed Grade of Bleeding (as Measured on WHO Bleeding Scale) During the Study Period | Grade 1 Bleeding | 2 Participants |
| Placebo | Highest Observed Grade of Bleeding (as Measured on WHO Bleeding Scale) During the Study Period | Grade 5 Bleeding | 0 Participants |
| Placebo | Highest Observed Grade of Bleeding (as Measured on WHO Bleeding Scale) During the Study Period | Grade 2 Bleeding | 3 Participants |
Secondary
Number of Days Alive and Without WHO Grade 2 Bleeding or Greater
Number of days alive and without WHO grade 2 bleeding or greater during the first 30 days post activation of study drug. Bleeding graded on a scale ranging from 1 (minor bleeding) through 4 (bleeding that is fatal or life-threatening).
Time frame: 30 days after activation of study drug
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tranexamic Acid | Number of Days Alive and Without WHO Grade 2 Bleeding or Greater | 5.5 days |
| Placebo | Number of Days Alive and Without WHO Grade 2 Bleeding or Greater | 10.4 days |
Secondary
Number of Platelet and Red Blood Cell Transfusions
Number of platelet and red blood cell 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 | Group | Value (MEDIAN) |
|---|---|---|---|
| Tranexamic Acid | Number of Platelet and Red Blood Cell Transfusions | Number of platelet transfusions per patient | 1.5 transfusions |
| Tranexamic Acid | Number of Platelet and Red Blood Cell Transfusions | Number of pRBC transfusions per patient | 0.5 transfusions |
| Placebo | Number of Platelet and Red Blood Cell Transfusions | Number of platelet transfusions per patient | 4 transfusions |
| Placebo | Number of Platelet and Red Blood Cell Transfusions | Number of pRBC transfusions per patient | 1 transfusions |
Secondary
The Occurrence of Thromboembolic Adverse Events and Serious Adverse Events
Any venous or arterial thrombosis on standard diagnostic imaging post-randomization
Time frame: From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tranexamic Acid | The Occurrence of Thromboembolic Adverse Events and Serious Adverse Events | 0 events |
| Placebo | The Occurrence of Thromboembolic Adverse Events and Serious Adverse Events | 0 events |
Secondary
World Health Organization (WHO) Bleeding Scale Grade 2 or Higher Bleeding
Proportion of patients with bleeding of WHO grade 2 or above, after activation of study drug. Bleeding graded on a scale ranging from 1 (minor bleeding) through 4 (bleeding that is fatal or life-threatening).
Time frame: 30 days after activation of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tranexamic Acid | World Health Organization (WHO) Bleeding Scale Grade 2 or Higher Bleeding | 0 Participants |
| Placebo | World Health Organization (WHO) Bleeding Scale Grade 2 or Higher Bleeding | 3 Participants |