Tranexamic Acid Use to Reduce Blood Transfusion in Pediatric Cancer Patients Undergoing Limb Salvage Procedure

NCT04410042 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: TXAKIDSNCI-2020-02984
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized double-blind control trial evaluating the use Tranexamic acid (TXA) to decrease blood loss and transfusion requirements in pediatric and young adult cancer patients undergoing a limb salvage procedure that frequently requires perioperative or post-operative transfusions of blood products. Primary Objective

• To evaluate the difference in intra-or post-operatively transfused blood volume (mL/kg) for patients undergoing limb salvage procedures of the distal femur or proximal tibia who are randomized to receive perioperative tranexamic acid (TXA) versus placebo. Secondary Objectives
• To evaluate changes in platelets and in hemoglobin from pre-op to post-op level for patients randomized to receive perioperative TXA versus placebo.
• To evaluate differences in post-operative daily surgical drain output for patients randomized to receive perioperative TXA versus placebo.
• To evaluate changes in estimated blood loss (EBL) for patients randomized to receive perioperative TXA versus placebo.
• To evaluate the association between the intra-or post-operatively transfused blood volume and estimated blood loss (EBL) for patients randomized to receive perioperative TXA and placebo, respectively. Exploratory Objectives
• To evaluate differences in functional outcomes post-operatively for patients randomized to receive perioperative TXA versus placebo.
• To explore if significant correlations are observed between parameters reported with rotational thromboelastometry (ROTEM®) and EBL and transfusion requirements in pediatric and young adult patients undergoing limb salvage procedure who are randomized to perioperative TXA versus placebo.
• To evaluate differences in the prevalence and management of wound complications such as superficial or periprosthetic infections, wound dehiscence, contact dermatitis, post- operative hematomas, or any other clinically significant wound complication between patients randomized to receive perioperative TXA versus placebo.

Conditions

Cancer of the Bone; Limb Salvage

Keywords

Blood Transfusion; Cancer of the bone; Distal femur; Limb Salvage; Malignant Bone Tumor; Placebo; Proximal tibia; Randomized; Tranexamic acid; TXA

Outcome Measures

Primary Outcomes (1)

• To Evaluate the Difference in intra-or Post-operatively Transfused Blood Volume (mL/kg) for Patients Undergoing Limb Salvage Procedures of the Distal Femur or Proximal Tibia Who Are Randomized to Receive Perioperative Tranexamic Acid (TXA) Versus Placebo.

  The intra-or post-operative volumes of transfused blood for both the TXA treated group and placebo group will be estimated with a two-sided 95% confidence interval. The blood volumes transfused per kilogram of body weight of the two groups (TXA vs. Placebo) will be evaluated using a two-sided student's t-test after log(1+x) transformation.

  intra- or post-operatively transfused blood volume (mL/kg), 6 months

Secondary Outcomes (7)

• To Evaluate Changes in Platelets From Pre-op to Post-op Level for Patients Randomized to Receive Perioperative TXA Versus Placebo.

  changes in platelets from pre-op to post-op level, 6 months

• To Evaluate Changes in Hemoglobin From Pre-op to Post-op Level for Patients Randomized to Receive Perioperative TXA Versus Placebo.

  changes in hemoglobin from pre-op to post-op level, 6 months

• To Evaluate Differences in Post-operative Daily Surgical Drain Output for Patients Randomized to Receive Perioperative TXA Versus Placebo.

  Conclusion of surgery to time of drain removal (prior to discharge from inpatient)

• To Evaluate Changes in Estimated Blood Loss (EBL) for Patients Randomized to Receive Perioperative TXA Versus Placebo.

  At conclusion of surgery

• To Evaluate Log Transfused Blood Volume Between the intra-or Post-operatively for Patients Randomized to Receive Perioperative TXA and Placebo, Respectively.

  At conclusion of surgery

Study Arms (2)

Tranexamic Acid

EXPERIMENTAL

At initiation of surgical preparation, participants randomized to the active treatment arm will receive tranexamic acid 10 mg/kg (max 1 g), given via syringe pump programmed to infuse over 15 minutes. If no unacceptable toxicities occur, a second dose of tranexamic acid IV push over 5 to 15 minutes will be given 6 hours (with a window of +/- 30 minutes) after the first dose (either intra- or post-operatively).

Drug: Tranexamic Acid

Placebo

PLACEBO COMPARATOR

At initiation of surgical preparation, participants randomized to the placebo treatment arm will receive 0.9% sodium chloride (salt water). It will be matched in appearance, volume, and administration to the active treatment arm with tranexamic acid. If no unacceptable toxicities occur, a second dose of placebo IV push over 5 to 15 minutes will be given 6 hours (with a window of +/- 30 minutes) after the first dose (either intra- or post-operatively).

Other: 0.9% sodium chloride

Interventions

Tranexamic Acid DRUG

Given IV

Also known as: Cyklokapron®

Tranexamic Acid

0.9% sodium chloride OTHER

Given IV

Also known as: Salt water

Placebo

Eligibility Criteria

• Age: Up to 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participant undergoing limb salvage procedure of malignant bone tumor of the distal femur or proximal tibia, which typically requires blood transfusions.
• Patient under the age of 25
• Adequate bone marrow function defined as:
• Upward trending peripheral absolute neutrophil count (ANC)
• Platelet count ≥ 100,000/mm\^3 (transfusion independent defined as no platelets required for 4 days)
• Hemoglobin ≥ 8.0 g/dL
• No RBC transfusion within 24 hours
• Adequate renal function defined as:
• Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73m\^2 OR
• Maximum serum creatinine based on age/gender as follows: Age 1 day to \< 1 years: maximum serum creatinine (mg/dL) 0.6 for males and 0.5 for females; Age 1 to \< 2 years: maximum serum creatinine (mg/dL) 0.6 for males and 0.6 for females; Age 2 to \< 6 years: maximum serum creatinine (mg/dL) 0.8 for males and 0.8 for females; Age 6 to \< 10 years: maximum serum creatinine (mg/dL) 1.0 for males and 1.0 for females; Age 10 to \< 13 years: maximum serum creatinine (mg/dL) 1.2 for males and 1.2 for females; Age 13 to \< 16 years: maximum serum creatinine (mg/dL) 1.5 for males and 1.4 for females; Age ≥ 16 years: maximum serum creatinine (mg/dL) 1.7 for males and 1.4 for females
• Adequate liver function defined as:
• Total bilirubin ≤ 1.5x the institutional upper limit of normal (IULN) for age
• ALT (SGPT) and AST (SGOT) ≤ 2.5x IULN for age (or \<5x IULN for patients with documented disease involving the liver or 10x IULN for patients receiving HDMTX)
• Serum albumin \> 2 g/dL
• Adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5

You may not qualify if:

• Participants whose limb salvage procedure may require significant manipulation of major blood vessels.
• Participants with known bone marrow deficiency resulting in red blood cell deficiency (e.g. Diamond-Blackfan anemia)
• Participants receiving erythropoietin-stimulating agents (e.g. epoetin alfa)
• Participants with active hemorrhagic cystitis (e.g. alkylator-induced) with gross hematuria or \>50 RBCs per high powered field on urinalysis
• Participants actively receiving all-trans retinoic acid (ATRA) or isotretinoin (Accutane)
• Participants with known allergies to antifibrinolytics
• Participants with known hypercoagulopathies
• Personal history of a thrombosis or active thrombus
• Participants currently on anticoagulation medications (e.g. warfarin, enoxaparin)
• Participants with a history of seizures. Patients with a history of febrile seizure are eligible.
• Persisting toxicity related to other systemic therapies (e.g. chemotherapy) which constitutes an unacceptable safety risk based on the judgment of the PI and/or the primary treating physician.
• Female participants who are currently pregnant or actively breastfeeding.
• Female participants who are currently receiving estrogen-based contraception therapy.
• Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.
• Participants enrolled in another clinical trial utilizing an IND/IDE experimental therapy.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital
• ClinicalTrials Open at St. Jude

MeSH Terms

Conditions

Bone Neoplasms

Interventions

Tranexamic Acid; Sodium Chloride; Fluoridation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Preventive Dentistry; Dentistry; Public Health Dentistry; Environment and Public Health

Results Point of Contact

• Title: Michael D. Neel, MD
• Organization: St. Jude Children's Research Hospital

mneel@orthosouth.org

901-259-1600

Study Officials

• Michael D. Neel, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: To allow for the study team and participants to remain blinded to the treatment assignment, the study drug will be labeled as Tranexamic Acid/Placebo (TXAKIDS) followed by applicable dose and administration instructions.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2020
• First Posted: June 1, 2020
• Study Start: January 29, 2021
• Primary Completion: January 16, 2024
• Study Completion: January 16, 2024
• Last Updated: December 20, 2024
• Results First Posted: December 5, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available at the time of article publication.
• Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

Locations

US (1)