Optimal Pediatric Heart Transplant Immunosuppression With MicroRNAs (OPTIMA)

Recruiting

• Conditions: Cardiac Failure; Graft Rejection

• Registration Number: NCT06532890
• Lead Sponsor: Inova Health Care Services

Brief Summary

This study aims to discover circulating microRNAs (associated with drug doses and levels) that can be used to characterize the overall immune state in pediatric heart transplant patients and predict patients that will go on to develop infection and rejection. MicroRNAs (miRs) are small, non-coding RNA molecules that regulate gene expression and serve as molecular biomarkers found in the circulation.

Detailed Description

The study objectives will be accomplished in a prospective, multicenter observational, longitudinal cohort study that includes 100-150 Pediatric Heart Transplant (PHT) patients from the United States. Patients will be screened for eligibility and enrolled \~1 month after PHT. Study participation will last 24 months.

All patients will follow the center's standard of care surveillance schedule after transplant. Blood samples will be collected for miR evaluation at:

1. specified time intervals after transplant and

2. when a clinical event of interest occurs, including rejection, infection, or major change in immunosuppression.

Research samples will be collected and used to evaluate microRNA expression as well as other biomarkers related to heart transplantation and immunosuppression medications. Additional data collection will include demographics, medical history, medications, human leukocyte (HLA)/donor specific antibody (DSA) evaluations, endomyocardial biopsy (EMB), echocardiography, donor-derived cell-free DNA (dd-cfDNA), and other post-transplant events and testing.

This work will form the basis for a non-invasive, genomic blood test that can be used to monitor patients after heart transplant to mitigate complications of over-immunosuppression, such as infection, without increasing the risks of under-immunosuppression, such as rejection.

Study Timeline

• Study First Submitted: 2024-07-29
• Study First Submitted QC: 2024-07-29
• Study First Posted: 2024-08-01
• Study Start: 2025-02-06
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-30
• Last Update Posted: 2025-05-01
• Primary Completion: 2029-10-01
• Study Completion: 2029-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

• Age ≤ 18 years at enrollment
• Receipt of orthotopic heart transplant (OHT) within the prior 1 month ± 2 weeks
• Planned follow-up at the transplant center for a minimum of one-year.
• Caregiver able and willing to comply with the study visit schedule, study procedures, and study requirements.

Exclusion Criteria

• Recipient of a multi-organ transplant
• History of prior solid organ transplant before the index heart transplant
• Ongoing mechanical circulatory support or hemodynamic instability
• Active infection requiring either a) hospitalization b) treatment with antimicrobial therapy or c) reduction in immunosuppression
• History of rejection prior to enrollment
• Inability to collect specified blood volume at enrollment +/- 1 week

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Time-to-Event Analysis of Circulating microRNAs (miRs) Predicting Rejection in Pediatric Heart Transplant Recipients	up to 2 years post-transplant	A time-to-event analysis will be performed to identify specific circulating microRNAs (miRs) that predict the risk of rejection in heart transplant recipients. Rejection is defined as treated rejection based on 1) endomyocardial biopsy (EMB) pathology, 2) unexplained graft dysfunction, or 3) molecular testing; leading to treatment with pulse dose steroids, monoclonal antibodies, plasmapheresis, and/or intravenous immunoglobulin (IVIg).; EMB Pathology: Acute Cellular Rejection (ACR) Grade ≥ 2R and/or Antibody-mediated Rejection (AMR) Grade ≥ pAMR1, per International Society for Heart and Lung Transplantation (ISHLT) grading systems.; Graft Dysfunction: Left Ventricular Ejection Fraction (LVEF) decline ≥ 10% from baseline and \< 50% absolute LVEF by echocardiography.; Molecular Testing: Presence of 2 of the following 3 criteria-presence of HLA-DSA, elevated donor-derived cell-free DNA (dd-cfDNA), or gene expression results from blood or EMB testing.
Time-to-Event Analysis of Circulating microRNAs (miRs) Predicting Infection in Pediatric Heart Transplant Recipients	up to 2 years post-transplant	A time-to-event analysis will be performed to identify specific circulating microRNAs (miRs) that predict the risk of infection in heart transplant recipients. Infections are defined as any bacterial, viral, fungal, or opportunistic infection leading to: 1) hospitalization, 2) prescription of antimicrobial therapy, or 3) reduction in immunosuppression.

Trial Locations

Locations (5)

Columbia University; 🇺🇸 New York, New York, United States

Texas Children's Hospital; 🇺🇸 Houston, Texas, United States

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

Monroe Carell Jr. Children's Hospital at Vanderbilt; 🇺🇸 Nashville, Tennessee, United States

Inova Health System; 🇺🇸 Falls Church, Virginia, United States