Pilot Trial of Pravastatin as a Novel Prophylactic Medicine to Reduce Endothelial Injury in Pediatric Patients With Elevated Body Mass Index
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Percentage of participants who developed clinically significant transaminitis, renal dysfunction and rhabdomyolysis
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Scheduled for allogeneic stem cell transplant
- •Ages ≥ 2 - ≤ 25 years old
- •Elevated BMI defined by the Center for Disease Control and Prevention definitions. Both overweight (BMI between 85th-94th percentile) and obese (BMI >95th percentile) patients are eligible
- •All diagnoses are eligible
排除标准
- •Patients with documented anaphylaxis to pravastatin
- •Patients will be ineligible if they are unable to take medication orally or enterally (i.e. intestinal failure)
- •Patients with elevations in ALT/AST levels 3x ULN at time of enrollment
- •Patients with renal impairment as clinically measured (GFR <50 ml/min/1.73m2) at time of enrollment
- •Patients with known neuromuscular and metabolic disorders associated with an increased risk of rhabdomyolysis (ie metabolic muscle disorders, mitochondrial disorders, and muscular dystrophies)
- •Patients taking any drugs that are known substrates for OATP1B1 and OATP1B3 transporters
研究组 & 干预措施
Pravastatin Prophylactic Treatment
干预措施: Pravastatin (Drug)
结局指标
主要结局
Percentage of participants who developed clinically significant transaminitis, renal dysfunction and rhabdomyolysis
时间窗: Until day 35 after bone marrow transplant when pravastatin is discontinued
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.
Percentage of participants who adhered to the medication plan
时间窗: Until day 35 after bone marrow transplant when pravastatin is discontinued
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.
次要结局
- Number of participants with overall survival(100 days after bone marrow transplant)
- Number of participants with graft failure(100 days after bone marrow transplant)
- Number of participants with primary disease relapse(100 days after bone marrow transplant)
- Median number of days until neutrophil engraftment(Through study completion, an average of up to 100 days)
- Median number of days until platelet engraftment(Through study completion, an average of up to 100 days)
- Assessment of SLCO1B1 genotyping(Baseline)
- Measurement of sphingosine-1-phosphate (S1P) levels in plasma(Weekly from admission until day 35 from bone marrow transplant)
- Number of participants who adhered to the medication plan(Through study completion, an average of 35 days after bone marrow transplant)