Chemotherapy and radiation used in patients undergoing bone marrow transplant (BMT) disrupts the endothelial lining (a thin layer of cells inside the blood vessels) which is found all throughout the body including the kidney, heart, lungs, and intestines. Disruption of this endothelial lining can lead to complications such as graft-vs-host disease (GVHD), thrombotic microangiopathy (TMA) and veno-occlusive disease (VOD). The purpose of this research study is to help investigators see if pravastatin is safe and well tolerated in patients undergoing BMT to see if it will reduce endothelial injury after BMT. The investigator hypothesizes that prophylactic pravastatin in pediatric allogeneic hematopoietic stem cell transplant recipients with elevated BMI is safe and feasible.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
25
Participants will receive pravastatin orally once daily through the first 35 days after bone marrow transplant.
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Percentage of participants who developed clinically significant transaminitis, renal dysfunction and rhabdomyolysis
Every enrolled patient will have routine liver function test (LFT) and renal function profile monitoring as part of their standardized transplant care. Transaminitis is expected and often multifactorial in the HSCT population, (i.e. preparative regimen, azole antifungal prophylaxis, or post-transplant complications such as infection and GVHD), therefore, we have determined modified parameters to hold or modify the dose of pravastatin. We will modify and/or hold pravastatin dosing at the time of transaminase elevations \> 3X upper limit of normal unless a clear-cut alternative explanation can be provided. Additionally, we will also check creatinine kinase (CK) levels on admission and once weekly while the patient is actively taking pravastatin to monitor for rhabdomyolysis.
Time frame: Until day 35 after bone marrow transplant when pravastatin is discontinued
Percentage of participants who adhered to the medication plan
Participants will be considered adhered to the medication plan if they took the study drug at least 70% of the time. Nursing documentation of pravastatin administration and drug diaries will be used as documentation of compliance.
Time frame: Until day 35 after bone marrow transplant when pravastatin is discontinued
Number of participants with overall survival
Time frame: 100 days after bone marrow transplant
Number of participants with graft failure
Graft failure is defined as follows: Primary graft failure is defined as no evidence of engraftment or hematological recovery of donor cells, within the first month after transplant, without evidence of disease relapse. Secondary graft failure refers to the loss of a previously functioning graft, resulting in cytopenia involving at least two blood cell lineages.
Time frame: 100 days after bone marrow transplant
Number of participants with primary disease relapse
Primary disease relapse is defined as: The return of a disease or the signs and symptoms of a disease after a period of improvement.
Time frame: 100 days after bone marrow transplant
Median number of days until neutrophil engraftment
Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 500 cells/mm3 (0.5 x 10\^9/L) or greater.
Time frame: Through study completion, an average of up to 100 days
Median number of days until platelet engraftment
Platelet engraftment is usually defined as independence from platelet transfusion for at least 7 days with a platelet count of more than \>20 × 10\^9/L
Time frame: Through study completion, an average of up to 100 days
Assessment of SLCO1B1 genotyping
The SLCO1B1 gene encodes for making the protein organic anion transporting polypeptide 1B1 (OATP1B1), which is the transporter for drugs, including statins, into the liver. Patients enrolled on study will have their SLCO1B1 genotyping performed from whole blood samples at baseline to determine how this affects their overall statin clearance.
Time frame: Baseline
Measurement of sphingosine-1-phosphate (S1P) levels in plasma
S1P levels will be measured on weekly intervals using mass spectrometry
Time frame: Weekly from admission until day 35 from bone marrow transplant
Number of participants who adhered to the medication plan
The lipid profile is a blood test that includes measurements of cholesterol, triglycerides, High-density lipoprotein (HDL) and Low-density lipoprotein (LDL). It is a routine test that monitors cholesterol levels. Pravastatin reduces cholesterol production. The lipid profile will be measured prior to the first dose of pravastatin. After the last dose of pravastatin the lipid profile will be measured. Any reduction in total cholesterol and LDL levels will be used as a surrogate marker for medication adherence.
Time frame: Through study completion, an average of 35 days after bone marrow transplant
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