A Pediatric Trial Using Tranexamic Acid in Thrombocytopenia

Phase 1

Terminated

Conditions: Hemostatic Disorder
Thrombocytopenia
Coagulation Defect; Acquired
Pediatric Cancer

Interventions: Drug: Normal saline
Drug: Tranexamic Acid

Registration Number: NCT03806556

Lead Sponsor: Meghan McCormick

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 11

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Normal saline	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.
Tranexamic Acid	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).

Primary Outcome Measures

Name	Time	Method
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.
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.

Secondary Outcome Measures

Name	Time	Method
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
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
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).
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).
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).
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

Trial Locations

Locations (1): UPMC Childrens Hospital of Pittsburgh
🇺🇸
Pittsburgh, Pennsylvania, United States
UPMC Childrens Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States