Tranexamic Acid for the Reduction of Blood Loss in Pediatric and Young Adult Cancer Patients Undergoing Surgery in a Lower Extremity, TXAKIDS Trial
This phase III trial compares tranexamic acid to salt water for the reduction of blood loss in pediatric and young adult patients with bone tumor undergoing surgery in a lower extremity. Tranexamic acid is a drug that helps blood to clot and may slow down bleeding during surgery. Giving tranexamic acid may work better at slowing down the amount of blood loss during surgery and ultimately reduce the amount of blood transfused during and after bone surgery compared to salt water.
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
- Upward trending peripheral absolute neutrophil count (ANC)
- Platelet count >= 100,000/mm^3 (transfusion independent defined as no platelets required for 4 days) (performed within 14 days prior to enrollment)
- Hemoglobin >= 8.0 g/dL (performed within 14 days prior to enrollment)
- No red blood cell (RBC) transfusion within 24 hours
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR maximum serum creatinine based on age/gender as follows: (threshold creatinine values were derived from the Schwartz formula for estimating GFR) * Age; maximum serum creatinine (mg/dL) ** 1 day to < 1 years; 0.6 (male), 0.5 (female) ** 1 to < 2 years; 0.6 (male), 0.6 (female) ** 2 to < 6 years; 0.8 (male), 0.8 (female) ** 6 to < 10 years; 1.0 (male), 1.0 (female) ** 10 to < 13 years; 1.2 (male), 1.2 (female) ** 13 to < 16 years; 1.5 (male) , 1.4 (female) ** >= 16 years; 1.7 (male), 1.4 (female)
- Total bilirubin =< 1.5 x the institutional upper limit of normal (IULN) for age (performed within 14 days prior to enrollment)
- Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) and aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 x IULN for age (or < 5 x IULN for patients with documented disease involving the liver or 10 x IULN for patients receiving HDMTX) (performed within 14 days prior to enrollment)
- Serum albumin > 2 g/dL (performed within 14 days prior to enrollment)
- International normalized ratio (INR) =< 1.5 (performed within 14 days prior to enrollment)
- 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 principal investigator (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 Investigational New Drug (IND)/Investigational Device Exemption (IDE) experimental therapy
- Participants with a history of central nervous system (CNS) disease
- Participants with known bleeding disorder
- Participants with known platelet dysfunction
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04410042.
PRIMARY OBJECTIVE:
I. 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:
I. To evaluate changes in platelets and in hemoglobin from pre-operative (pre-op) to post-operative (post-op) level for patients randomized to receive perioperative TXA versus placebo.
II. To evaluate differences in post-operative daily surgical drain output for patients randomized to receive perioperative TXA versus placebo.
III. To evaluate changes in estimated blood loss (EBL) for patients randomized to receive perioperative TXA versus placebo.
IV. 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:
I. To evaluate differences in functional outcomes post-operatively for patients randomized to receive perioperative TXA versus placebo.
II. 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.
III. 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.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Before surgery, patients receive tranexamic acid intravenously (IV) over 15 minutes. If no unacceptable toxicities occur, 6 hours after the first dose patients receive a second dose tranexamic acid IV over 5-15 minutes.
ARM II: Before surgery, patients receive placebo IV over 15 minutes. If no unacceptable toxicities occur, 6 hours after the first dose patients receive a second dose placebo IV over 5-15 minutes.
Trial PhasePhase III
Trial Typesupportive care
Lead OrganizationSaint Jude Children's Research Hospital
Principal InvestigatorMichael Daniel Neel
- Primary IDTXAKIDS
- Secondary IDsNCI-2020-02984
- ClinicalTrials.gov IDNCT04410042