A Pediatric Trial Using Tranexamic Acid in Thrombocytopenia

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Pediatric Trial Using Tranexamic Acid in Thrombocytopenia

Conditions
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Pediatric Cancer, Thrombocytopenia, Hemostatic Disorder, Coagulation Defect; Acquired

Intervention / Treatment
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* Drug: Tranexamic Acid
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tranexamic Acid<br>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). | Drug: Tranexamic Acid<br>* IV medication administered after patient meets inclusion/exclusion criteria<br>* Other names: TXA;|
| Placebo Comparator: Placebo<br>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. | Drug: Normal saline<br>* IV medication administered after patient meets inclusion/exclusion criteria<br>* Other names: NS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug | 
| 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. | From time of recruitment of the first patient until the last patient is enrolled, up to 16 months in duration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 30 days after activation of study drug | 
| 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 | 30 days after activation of study drug | 
| 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). | 30 days after activation of study drug | 
| The Occurrence of Thromboembolic Adverse Events and Serious Adverse Events | Any venous or arterial thrombosis on standard diagnostic imaging post-randomization | From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug | 
| Bleeding of Any Grade | Proportion of patients with bleeding of any grade as assessed by WHO bleeding score, after activation of study drug | From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug | 
| 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). | From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tranexamic acid, anti-fibrinolytic agents, chemotherapy-induced thrombocytopenia