Pravastatin as a Prophylactic to Reduce Endothelial Injury in Pediatric Patients With Elevated Body Mass Index

NCT05524246 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 2022-0308
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hematopoietic Stem Cell Transplant (HSCT); Endothelial Injury

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Until day 35 after bone marrow transplant when pravastatin is discontinued

Secondary Outcomes (8)

• 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

Study Arms (1)

Pravastatin Prophylactic Treatment

EXPERIMENTAL

Drug: Pravastatin

Interventions

Pravastatin DRUG

Participants will receive pravastatin orally once daily through the first 35 days after bone marrow transplant.

Pravastatin Prophylactic Treatment

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Interventions

Pravastatin

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Jane Koo, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2022
• First Posted: September 1, 2022
• Study Start: January 27, 2023
• Primary Completion: December 31, 2024
• Study Completion: March 5, 2025
• Last Updated: April 18, 2025

Record last verified: 2025-04

Locations

US (1)