A Pediatric Trial Using Tranexamic Acid in Thrombocytopenia

NCT03806556 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: PRO18100519
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

tranexamic acid; anti-fibrinolytic agents; chemotherapy-induced thrombocytopenia

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• World Health Organization (WHO) Bleeding Scale Grade 2 or Higher Bleeding

  30 days after activation of study drug

• Number of Platelet and Red Blood Cell Transfusions

  30 days after activation of study drug

• Number of Days Alive and Without WHO Grade 2 Bleeding or Greater

  30 days after activation of study drug

• 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

• Bleeding of Any Grade

  From activation of the study drug (maximum 30 days) through 30 days from discontinuation of study drug

Study Arms (2)

Tranexamic Acid

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Tranexamic Acid DRUG

IV medication administered after patient meets inclusion/exclusion criteria

Also known as: TXA

Tranexamic Acid

Normal saline DRUG

IV medication administered after patient meets inclusion/exclusion criteria

Also known as: NS

Placebo

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Meghan McCormick: lead

Study Sites (1)

UPMC Childrens Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

MeSH Terms

Conditions

Neoplasms; Thrombocytopenia; Hemostatic Disorders

Interventions

Tranexamic Acid; Saline Solution

Condition Hierarchy (Ancestors)

Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

The pre-specified analysis described in the study protocol stated the following: "For secondary endpoints, events of WHO Grade 2 or higher bleeding will be compared through the use of odds ratio or T-test statistic of means. The mean number of platelet transfusions will be analyzed using a T-test statistic of means." This analysis was not completed as it would be scientifically inappropriate due to insufficient enrollment. Instead a descriptive analysis was completed.

Results Point of Contact

• Title: Meghan McCormick, MD MS
• Organization: University of Pittsburgh Medical Center

meghan.mccormick3@chp.edu

412-692-6938

Study Officials

• Meghan McCormick, MD

  UPMC Childrens Hospital of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Fellow

Model Details: 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.

Study Record Dates

• First Submitted: January 4, 2019
• First Posted: January 16, 2019
• Study Start: April 22, 2019
• Primary Completion: August 25, 2020
• Study Completion: August 25, 2020
• Last Updated: September 20, 2021
• Results First Posted: September 20, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Beginning within 1 year and ending 5 years after trial completion
• Access Criteria: Researchers who provide a methodologically sound proposal may request data. Proposals should be directed to meghan.mccormick3@chp.edu. To gain access data requestors will need to sign a data access agreement.

Locations

US (1)