HEARTBiT: Multi-Marker Blood Test for Acute Cardiac Transplant Rejection (HEARTBiT)
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|ClinicalTrials.gov Identifier: NCT03575910|
Recruitment Status : Recruiting
First Posted : July 3, 2018
Last Update Posted : June 19, 2019
|Condition or disease|
|Heart Transplant Failure and Rejection Heart Failure Heart Diseases Heart Failure，Congestive Transplant; Failure, Heart Transplant Failure|
Cardiac transplantation remains the main intervention for those with end-stage heart failure. Maintenance immunosuppression is given to all transplant recipients to prevent acute rejection and loss of the allograft. Despite great improvements in immunosuppressive therapies, acute rejection remains a clinical problem and occurs at varying severity in 20-30% of patients within the first 3 months post-transplant. Timely detection of moderate rejection allows for treatment to be modified, preventing organ damage, graft failure and patient death. The current method to monitor for rejection remains the endomyocardial biopsy (EMB), a highly invasive and costly procedure that poses physical risks and emotional stress to patients, who must undergo 12-15 such tests during the first year post-transplant. EMB detects rejection only when tissue damage has occurred, and lacks sensitivity as it provides information about tiny pieces of the endomyocardium. Clearly, patients and clinicians would benefit from an effective, cheaper, less invasive diagnostic test that can indicate when an EMB is not needed.
Our team used unbiased omics strategies and computational tools to identify potential biomarkers of treatable acute rejection (ISHLT grade 2R or higher) in peripheral blood. We hypothesize that there are distinctive RNA and protein signatures in blood that can be developed into a simple test to accurately indicate when heart transplant patients do not require EMB, and that studying these biomarkers in a clinically relevant setting will facilitate clinical adoption.
Our Specific Aims are to:
- Evaluate the performance of HEARTBiT, a custom 9-mRNA biomarker test developed on the NanoString platform, in an environment suitable for clinical translation, on >4000 newly collected samples from 400 patients across North America
- Examine the biomarker panel score and individual biomarkers serially across the first year post-transplant to identify predictive signatures of rejection and characterize underlying biology
- Develop and assess 5 promising protein biomarker candidates on NanoString, test 7 candidate miRNAs, and evaluate combinatorial RNA-protein classifier performance metrics to improve HEARTBiT
Expertise: Our team at the Centre of Excellence for Prevention of Organ Failure has over 10 years experience in computational analysis of omics and clinical data to create biomarker tests that out-perform current gold standards. Our Biomarkers in Transplantation (BiT) study has been continuously funded by competitive grants, philanthropy and industry between 2004-2017 and has generated many publications related to heart and kidney transplant rejection. Via our collaborators, we will have access to a Canadian Blood Services facility for testing our biomarkers, and patient samples from 5 major transplant sites (St. Paul's/Vancouver, Toronto, Nebraska, Newark Beth Israel, Duke).
Outcomes: The HEARTBiT test will be ready for clinical utility studies. The test will have significant clinical and socioeconomic value by reducing EMBs for transplant patients and enabling the tailoring of therapy. Insights into the biology of immune rejection will also be enhanced.
|Study Type :||Observational|
|Estimated Enrollment :||400 participants|
|Official Title:||HEARTBiT: A Novel Multi-Marker Blood Test for Management of Acute Cardiac Allograft Rejection|
|Actual Study Start Date :||August 9, 2018|
|Estimated Primary Completion Date :||June 30, 2021|
|Estimated Study Completion Date :||June 30, 2023|
Acute Rejection (AR)
Heart transplant patients diagnosed with an ISHLT grade 2R or 3R via endomyocardial biopsy.
Mild Rejection (MR)
Heart transplant patients diagnosed with an ISHLT grade 1R via endomyocardial biopsy.
Heart transplant patients diagnosed with an ISHLT grade 0R via endomyocardial biopsy.
- Comparison of the HEARTBiT Biomarker Panel Score (BPS) between acute rejection and non-rejection/mild-rejection samples on the NanoString platform. [ Time Frame: Within 5 years ]The performance of HEARTBiT, a custom 9-RNA biomarker assay developed on the NanoString platform, will be evaluated in an environment suitable for clinical translation using a sample size of ~4000 newly collected samples from 400 HT patients. Performance will be assessed by applying an algorithm that combines the quantitative data of the 9 RNA into a single BPS. This score aggregates the influence of all RNAs and will be associated with an estimated probability that AR is occurring in the transplant recipient. The algorithm will establish a single cutoff thus producing a final binary test result (AR or NR/MR), or, if possible, two cutoffs to separate AR, MR and NR as ordered variables.
Biospecimen Retention: Samples With DNA
Whole blood samples to be collected in four (4) tubes (approx. 15mL or 3 teaspoons) consisting of:
- 1 - 6 mL lavender top (EDTA) tube (plasma)
- 1 - 4 mL red top tube (serum)
- 2 - 2.5 mL PAXgene tubes (RNA)
Blood processing (fractionation) of plasma and serum tubes following SOP guidelines will result in collection of:
8 - 0.5mL plasma aliquots
1 - 0.5mL buffy coat DNA sample 6 - 0.5mL serum aliquots
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03575910
|Contact: Sara Assadian, MHS, CCRP||604-682-2344 ext firstname.lastname@example.org|
|Contact: Karen Lam, PhD||604-682-2344 ext email@example.com|
|United States, Nebraska|
|University of Nebraska Medical Center||Recruiting|
|Omaha, Nebraska, United States, 68198|
|Contact: Sandra J Strizek, BSRT, RRT 402-559-0983 firstname.lastname@example.org|
|Canada, British Columbia|
|St. Paul's Hospital||Recruiting|
|Vancouver, British Columbia, Canada, V6Z 1Y6|
|Contact: Sara Assadian, MHS, CCRP 604-682-2344 ext 62557 email@example.com|
|Principal Investigator: Bruce M McManus, MD, PhD|
|Ottawa Heart Institute||Recruiting|
|Ottawa, Ontario, Canada, K1Y4W7|
|Contact: Heather Cosgrove 6136967000 ext 14790 firstname.lastname@example.org|
|Toronto General Hospital UHN||Recruiting|
|Toronto, Ontario, Canada, M5G 2C4|
|Contact: Natalia Nugaeva, PhD, CCRP 416-340-4800 ext 3403 Natalia.Nugaeva@uhn.ca|
|Principal Investigator:||Bruce McManus, MD, PhD||University of British Columbia|