Clinical trial NCT04410042: Tranexamic Acid Use to Reduce Blood Transfusion in Pediatric Cancer Patients Undergoing Limb Salvage Procedure
Official title: Tranexamic Acid (TXA) to Reduce Volume Of Blood Transfused In Pediatric And Young Adult Cancer Patients Undergoing Limb Salvage Procedure Of A Lower Extremity
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
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
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
First posted: 2020-06-01
Enrollment: 15
Sex: ALL
Maximum age (years): 24
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Detailed description: Eligible participants undergoing limb salvage procedures will be randomized to receive either tranexamic acid (TXA) or placebo peri-operatively.

The initial dose of tranexamic acid/placebo will be given at the initiation of surgical preparation. The second dose will be given 6 hours after the first dose (either intraoperatively or post-operatively). All doses will be given intravenously. Doses will be double blinded and randomized for each surgical procedure.

Eligibility criteria: Inclusion Criteria:

* 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
* Female participants of child-bearing potential (\>10 years old) must have a negative serum or urine pregnancy test within 72 hours of sedation

Exclusion Criteria:

* 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.
* Participants with a history of CNS disease.
* Participants with known bleeding disorder.
* Participants with known platelet dysfunction.

Primary outcomes:
measure: 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.
timeFrame: intra- or post-operatively transfused blood volume (mL/kg), 6 months
Secondary outcomes:
measure: To Evaluate Changes in Platelets From Pre-op to Post-op Level for Patients Randomized to Receive Perioperative TXA Versus Placebo.
timeFrame: changes in platelets from pre-op to post-op level, 6 months
measure: To Evaluate Changes in Hemoglobin From Pre-op to Post-op Level for Patients Randomized to Receive Perioperative TXA Versus Placebo.
timeFrame: changes in hemoglobin from pre-op to post-op level, 6 months
measure: To Evaluate Differences in Post-operative Daily Surgical Drain Output for Patients Randomized to Receive Perioperative TXA Versus Placebo.
timeFrame: Conclusion of surgery to time of drain removal (prior to discharge from inpatient)
measure: To Evaluate Changes in Estimated Blood Loss (EBL) for Patients Randomized to Receive Perioperative TXA Versus Placebo.
timeFrame: At conclusion of surgery
measure: To Evaluate Log Transfused Blood Volume Between the intra-or Post-operatively for Patients Randomized to Receive Perioperative TXA and Placebo, Respectively.
timeFrame: At conclusion of surgery
measure: To Evaluate Log Estimated Blood Loss (EBL) Between the intra-or Post-operatively for Patients Randomized to Receive Perioperative TXA and Placebo, Respectively.
timeFrame: At conclusion of surgery
measure: 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.
timeFrame: At conclusion of surgery
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Michael D. Neel, MD
role: PRINCIPAL_INVESTIGATOR
References: