Heart Transplant Failure and RejectionHEARTBiTNCT03575910
HEARTBiT: Multi-Marker Blood Test for Acute Cardiac Transplant Rejection
An observational study of Heart Transplant Failure and Rejection and Heart Failure, run by University of British Columbia at 4 sites in 2 countries.
Trial summary
Heart transplantation is a life saving therapy for people with end stage heart failure. Acute rejection, a process where the immune system recognizes the transplanted heart as foreign and mounts a response against it, remains a clinical problem despite improvements in immunosuppressive drugs. Read more about this study
- Who is it for?
- Ages 19 years and olderHealthy volunteers can take part
- Conditions the study is for
- Heart Transplant Failure and Rejection, Heart Failure, Heart Diseases
- How many people
- 196 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 9 Aug 2018to 30 Mar 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: It is anticipated that up to 400 heart transplant recipients will be enrolled as participants. Given the prevalence of treatable AR observed at the recruiting sites, 40-50 AR and 350 NR/MR are expected, excluding the time course (first year post-transplant) samples. Additionally, we plan on enrolling 30 normal control subjects. Comparisons will be made between AR, MR, and NR samples from independent patients.
Who may be able to join
- recipients who are ≥ 19 years of age
- willing and able to provide informed consent
- all individuals who are ≥ 19 years of age
- willing and able to provide informed consent
Who cannot join
- recipients under 19 years of age
- recipients who have received multiple, different solid organ transplants (i.e. a heart and a kidney)
- recipients who are HIV positive
- recipients of organs from donors who test positive for HIV
- Normal Subjects:
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Canada3 sites
Ottawa Heart Institute
Ottawa, Ontario, K1Y4W7
Toronto General Hospital UHN
Toronto, Ontario, M5G 2C4
St. Paul's Hospital
Vancouver, British Columbia, V6Z 1Y6
United States1 site
University of Nebraska Medical Center
Omaha, Nebraska, 68198
About this study
Official title: HEARTBiT: A Novel Multi-Marker Blood Test for Management of Acute Cardiac Allograft Rejection
Heart transplantation is a life saving therapy for people with end stage heart failure. Acute rejection, a process where the immune system recognizes the transplanted heart as foreign and mounts a response against it, remains a clinical problem despite improvements in immunosuppressive drugs. Acute rejection occurs in 20-30% of patients within the first 3 months post-transplant, and is currently detected by highly invasive heart tissue biopsies that happen 12-15 times in the first year post-transplant. Replacing the biopsy with a simple blood test is of utmost value to patients and will reduce healthcare costs. The goal of our project is to develop a new blood test to monitor heart transplant rejection. Advances in biotechnology have enabled simultaneous measurement of many molecules (e.g., proteins, nucleic acids) in blood, driving the development of new diagnostics. Our team is a leader in using computational tools to combine information from numerous biological molecules and clinical data to generate "biomarker panels" that are more powerful than existing diagnostic tests. Our sophisticated analytic methods has recently derived HEARTBiT, a promising test of acute rejection comprising 9 RNA biomarkers, from the measurement of 30,000 blood molecules in 150 Canadian heart transplant patients. Our objective is to study a custom-built HEARTBiT test in a setting and on a technology that enable clinical adoption. We will evaluate the new test on 400 new patients from 5 North American transplant centres. We will also track patients' HEARTBiT scores over time to help predict future rejection, and explore use of proteins and micoRNAs to improve HEARTBiT. Our work will provide the basis for a future clinical trial. The significance of this work rests in that it will provide a tool to identify acute cardiac rejection in a fast, accurate, cost-effective and minimally invasive manner, allowing for facile long-term monitoring and therapy tailoring for heart transplant patients.
Read the detailed description
Rationale:
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.
- Conditions
- Heart Transplant Failure and Rejection, Heart Failure, Heart Diseases, Heart Failure，Congestive, Transplant; Failure, Heart, Transplant Failure
- Keywords
- Heart, Transplantation, Acute cardiac rejection, Biomarkers, Genomics
- Medical subject headings
- Rejection, Psychology, Heart Failure, Heart Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. | |
| Non-Rejection (NR) | Heart transplant patients diagnosed with an ISHLT grade 0R via endomyocardial biopsy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of the HEARTBiT Biomarker Panel Score (BPS) between acute rejection and non-rejection/mild-rejection samples on the NanoString platform.
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.
Measured: Within 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2018
- Study start9 Aug 2018
- Primary completion30 Dec 2025
- Study completion30 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Heart Transplant Failure and RejectionStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 196 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), PROOF Centre of Excellence, Duke University, University of Nebraska, Toronto General Hospital, St. Paul's Hospital, Canada
- Responsible party
- Principal investigator, Scott Tebbutt, University of British Columbia
- Investigators
- Scott Tebbutt, PhD, Principal investigator, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03575910
- Sponsor's protocol ID
- PROOF
- Acronym
- HEARTBiT
- Status last verified
- Apr 2026
- First submitted
- 19 Jun 2018
- Last updated
- 4 May 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Sukma Dewi I, Gidlof O, Hollander Z, Lam KK, Benson MD, Braun OO, Nilsson J, Tebbutt SJ, Ng RT, Ohman J, McManus BM, Smith JG. Immunological Serum Protein Profiles for Noninvasive Detection of Acute Cellular Rejection After Heart Transplantation. J Am Coll Cardiol. 2017 Dec 12;70(23):2946-2947. doi: 10.1016/j.jacc.2017.10.012. No abstract available.
PubMed 29216990Toma M, Mak GJ, Chen V, Hollander Z, Shannon CP, Lam KKY, Ng RT, Tebbutt SJ, Wilson-McManus JE, Ignaszewski A, Anderson T, Dyck JRB, Howlett J, Ezekowitz J, McManus BM, Oudit GY. Differentiating heart failure phenotypes using sex-specific transcriptomic and proteomic biomarker panels. ESC Heart Fail. 2017 Aug;4(3):301-311. doi: 10.1002/ehf2.12136. Epub 2017 Mar 4.
PubMed 28772032Sukma Dewi I, Hollander Z, Lam KK, McManus JW, Tebbutt SJ, Ng RT, Keown PA, McMaster RW, McManus BM, Gidlof O, Ohman J. Association of Serum MiR-142-3p and MiR-101-3p Levels with Acute Cellular Rejection after Heart Transplantation. PLoS One. 2017 Jan 26;12(1):e0170842. doi: 10.1371/journal.pone.0170842. eCollection 2017.
PubMed 28125729Sukma Dewi I, Celik S, Karlsson A, Hollander Z, Lam K, McManus JW, Tebbutt S, Ng R, Keown P, McMaster R, McManus B, Ohman J, Gidlof O. Exosomal miR-142-3p is increased during cardiac allograft rejection and augments vascular permeability through down-regulation of endothelial RAB11FIP2 expression. Cardiovasc Res. 2017 Apr 1;113(5):440-452. doi: 10.1093/cvr/cvw244.
PubMed 28073833Hollander Z, Lazarova M, Lam KK, Ignaszewski A, Oudit GY, Dyck JR, Schreiner G, Pauwels J, Chen V, Cohen Freue GV, Ng RT, Wilson-McManus JE, Balshaw R, Tebbutt SJ, McMaster RW, Keown PA, McManus BM; NCE CECR PROOF Prevention of Organ Failure (PROOF) Centre of Excellence. Proteomic biomarkers of recovered heart function. Eur J Heart Fail. 2014 May;16(5):551-9. doi: 10.1002/ejhf.65. Epub 2014 Feb 23.
PubMed 24574204Shin H, Gunther O, Hollander Z, Wilson-McManus JE, Ng RT, Balshaw R, Keown PA, McMaster R, McManus BM, Isbel NM, Knoll G, Tebbutt SJ. Longitudinal analysis of whole blood transcriptomes to explore molecular signatures associated with acute renal allograft rejection. Bioinform Biol Insights. 2014 Jan 22;8:17-33. doi: 10.4137/BBI.S13376.. eCollection 2014.
PubMed 24526836Cohen Freue GV, Meredith A, Smith D, Bergman A, Sasaki M, Lam KK, Hollander Z, Opushneva N, Takhar M, Lin D, Wilson-McManus J, Balshaw R, Keown PA, Borchers CH, McManus B, Ng RT, McMaster WR; Biomarkers in Transplantation and the NCE CECR Prevention of Organ Failure Centre of Excellence Teams. Computational biomarker pipeline from discovery to clinical implementation: plasma proteomic biomarkers for cardiac transplantation. PLoS Comput Biol. 2013 Apr;9(4):e1002963. doi: 10.1371/journal.pcbi.1002963. Epub 2013 Apr 4.
PubMed 23592955Hollander Z, Chen V, Sidhu K, Lin D, Ng RT, Balshaw R, Cohen-Freue GV, Ignaszewski A, Imai C, Kaan A, Tebbutt SJ, Wilson-McManus JE, McMaster RW, Keown PA, McManus BM; NCE CECR PROOF Centre of Excellence. Predicting acute cardiac rejection from donor heart and pre-transplant recipient blood gene expression. J Heart Lung Transplant. 2013 Feb;32(2):259-65. doi: 10.1016/j.healun.2012.11.008. Epub 2012 Dec 21.
PubMed 23265908Shannon CP, Hollander Z, Wilson-McManus J, Balshaw R, Ng RT, McMaster R, McManus BM, Keown PA, Tebbutt SJ. White blood cell differentials enrich whole blood expression data in the context of acute cardiac allograft rejection. Bioinform Biol Insights. 2012;6:49-61. doi: 10.4137/BBI.S9197. Epub 2012 Apr 10.
PubMed 22550401Lin D, Hollander Z, Meredith A, Stadnick E, Sasaki M, Cohen Freue G, Qasimi P, Mui A, Ng RT, Balshaw R, Wilson-McManus JE, Wishart D, Hau D, Keown PA, McMaster R, McManus BM; Biomarkers in Transplantation Team; NCE CECR PROOF Centre of Excellence. Molecular signatures of end-stage heart failure. J Card Fail. 2011 Oct;17(10):867-74. doi: 10.1016/j.cardfail.2011.07.001. Epub 2011 Sep 3.
PubMed 21962426Hollander Z, Lin D, Chen V, Ng R, Wilson-McManus J, Ignaszewski A, Cohen Freue G, Balshaw R, Mui A, McMaster R, Keown PA, McManus BM; NCE CECR PROOF Centre of Excellence. Whole blood biomarkers of acute cardiac allograft rejection: double-crossing the biopsy. Transplantation. 2010 Dec 27;90(12):1388-93. doi: 10.1097/TP.0b013e3182003df6.
PubMed 21076371Lin D, Hollander Z, Ng RT, Imai C, Ignaszewski A, Balshaw R, Freue GC, Wilson-McManus JE, Qasimi P, Meredith A, Mui A, Triche T, McMaster R, Keown PA, McManus BM; Biomarkers in Transplantation Team; NCE CECR Centre of Excellence for the Prevention of Organ Failure. Whole blood genomic biomarkers of acute cardiac allograft rejection. J Heart Lung Transplant. 2009 Sep;28(9):927-35. doi: 10.1016/j.healun.2009.04.025.
PubMed 19716046
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HEARTBiT: A Novel Multi-Marker Blood Test for Management of Acute Cardiac Allograft Rejection
- ClinicalTrials.gov ID
- NCT03575910
- Acronym / sponsor ID
- HEARTBiT / PROOF
- Conditions
- Heart Transplant Failure and Rejection, Heart Failure, Heart Diseases, Heart Failure，Congestive, Transplant; Failure, Heart, Transplant Failure
- Keywords
- Heart, Transplantation, Acute cardiac rejection, Biomarkers, Genomics
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 196 participants (actual)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), PROOF Centre of Excellence, Duke University, University of Nebraska, Toronto General Hospital, St. Paul's Hospital, Canada
- Study start
- 9 Aug 2018 (actual)
- Primary completion
- 30 Dec 2025 (actual)
- Study completion
- 30 Mar 2026 (actual)
- First posted
- 3 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Heart transplantation is a life saving therapy for people with end stage heart failure. Acute rejection, a process where the immune system recognizes the transplanted heart as foreign and mounts a response against it, remains a clinical problem despite improvements in immunosuppressive drugs. Acute rejection occurs in 20-30% of patients within the first 3 months post-transplant, and is currently detected by highly invasive heart tissue biopsies that happen 12-15 times in the first year post-transplant. Replacing the biopsy with a simple blood test is of utmost value to patients and will reduce healthcare costs. The goal of our project is to develop a new blood test to monitor heart transplant rejection. Advances in biotechnology have enabled simultaneous measurement of many molecules (e.g., proteins, nucleic acids) in blood, driving the development of new diagnostics. Our team is a leader in using computational tools to combine information from numerous biological molecules and clinical data to generate "biomarker panels" that are more powerful than existing diagnostic tests. Our sophisticated analytic methods has recently derived HEARTBiT, a promising test of acute rejection comprising 9 RNA biomarkers, from the measurement of 30,000 blood molecules in 150 Canadian heart transplant patients. Our objective is to study a custom-built HEARTBiT test in a setting and on a technology that enable clinical adoption. We will evaluate the new test on 400 new patients from 5 North American transplant centres. We will also track patients' HEARTBiT scores over time to help predict future rejection, and explore use of proteins and micoRNAs to improve HEARTBiT. Our work will provide the basis for a future clinical trial. The significance of this work rests in that it will provide a tool to identify acute cardiac rejection in a fast, accurate, cost-effective and minimally invasive manner, allowing for facile long-term monitoring and therapy tailoring for heart transplant patients.
Detailed description
Rationale:
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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. |
| Non-Rejection (NR) | – | –Heart transplant patients diagnosed with an ISHLT grade 0R via endomyocardial biopsy. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- It is anticipated that up to 400 heart transplant recipients will be enrolled as participants. Given the prevalence of treatable AR observed at the recruiting sites, 40-50 AR and 350 NR/MR are expected, excluding the time course (first year post-transplant) samples. Additionally, we plan on enrolling 30 normal control subjects. Comparisons will be made between AR, MR, and NR samples from independent patients.
Key inclusion criteria (4 listed)
- recipients who are ≥ 19 years of age
- willing and able to provide informed consent
- all individuals who are ≥ 19 years of age
- willing and able to provide informed consent
Key exclusion criteria (5 listed)
- recipients under 19 years of age
- recipients who have received multiple, different solid organ transplants (i.e. a heart and a kidney)
- recipients who are HIV positive
- recipients of organs from donors who test positive for HIV
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2026.
- Background: PubMed 29216990Sukma Dewi I, Gidlof O, Hollander Z, Lam KK, Benson MD, Braun OO, Nilsson J, Tebbutt SJ, Ng RT, Ohman J, McManus BM, Smith JG. Immunological Serum Protein Profiles for Noninvasive Detection of Acute Cellular Rejection After Heart Transplantation. J Am Coll Cardiol. 2017 Dec 12;70(23):2946-2947. doi: 10.1016/j.jacc.2017.10.012. No abstract available.
- Background: PubMed 28772032Toma M, Mak GJ, Chen V, Hollander Z, Shannon CP, Lam KKY, Ng RT, Tebbutt SJ, Wilson-McManus JE, Ignaszewski A, Anderson T, Dyck JRB, Howlett J, Ezekowitz J, McManus BM, Oudit GY. Differentiating heart failure phenotypes using sex-specific transcriptomic and proteomic biomarker panels. ESC Heart Fail. 2017 Aug;4(3):301-311. doi: 10.1002/ehf2.12136. Epub 2017 Mar 4.
- Background: PubMed 28125729Sukma Dewi I, Hollander Z, Lam KK, McManus JW, Tebbutt SJ, Ng RT, Keown PA, McMaster RW, McManus BM, Gidlof O, Ohman J. Association of Serum MiR-142-3p and MiR-101-3p Levels with Acute Cellular Rejection after Heart Transplantation. PLoS One. 2017 Jan 26;12(1):e0170842. doi: 10.1371/journal.pone.0170842. eCollection 2017.
- Background: PubMed 28073833Sukma Dewi I, Celik S, Karlsson A, Hollander Z, Lam K, McManus JW, Tebbutt S, Ng R, Keown P, McMaster R, McManus B, Ohman J, Gidlof O. Exosomal miR-142-3p is increased during cardiac allograft rejection and augments vascular permeability through down-regulation of endothelial RAB11FIP2 expression. Cardiovasc Res. 2017 Apr 1;113(5):440-452. doi: 10.1093/cvr/cvw244.
- Background: PubMed 24574204Hollander Z, Lazarova M, Lam KK, Ignaszewski A, Oudit GY, Dyck JR, Schreiner G, Pauwels J, Chen V, Cohen Freue GV, Ng RT, Wilson-McManus JE, Balshaw R, Tebbutt SJ, McMaster RW, Keown PA, McManus BM; NCE CECR PROOF Prevention of Organ Failure (PROOF) Centre of Excellence. Proteomic biomarkers of recovered heart function. Eur J Heart Fail. 2014 May;16(5):551-9. doi: 10.1002/ejhf.65. Epub 2014 Feb 23.
- Background: PubMed 24526836Shin H, Gunther O, Hollander Z, Wilson-McManus JE, Ng RT, Balshaw R, Keown PA, McMaster R, McManus BM, Isbel NM, Knoll G, Tebbutt SJ. Longitudinal analysis of whole blood transcriptomes to explore molecular signatures associated with acute renal allograft rejection. Bioinform Biol Insights. 2014 Jan 22;8:17-33. doi: 10.4137/BBI.S13376.. eCollection 2014.
- Background: PubMed 23592955Cohen Freue GV, Meredith A, Smith D, Bergman A, Sasaki M, Lam KK, Hollander Z, Opushneva N, Takhar M, Lin D, Wilson-McManus J, Balshaw R, Keown PA, Borchers CH, McManus B, Ng RT, McMaster WR; Biomarkers in Transplantation and the NCE CECR Prevention of Organ Failure Centre of Excellence Teams. Computational biomarker pipeline from discovery to clinical implementation: plasma proteomic biomarkers for cardiac transplantation. PLoS Comput Biol. 2013 Apr;9(4):e1002963. doi: 10.1371/journal.pcbi.1002963. Epub 2013 Apr 4.
- Background: PubMed 23265908Hollander Z, Chen V, Sidhu K, Lin D, Ng RT, Balshaw R, Cohen-Freue GV, Ignaszewski A, Imai C, Kaan A, Tebbutt SJ, Wilson-McManus JE, McMaster RW, Keown PA, McManus BM; NCE CECR PROOF Centre of Excellence. Predicting acute cardiac rejection from donor heart and pre-transplant recipient blood gene expression. J Heart Lung Transplant. 2013 Feb;32(2):259-65. doi: 10.1016/j.healun.2012.11.008. Epub 2012 Dec 21.
- Background: PubMed 22550401Shannon CP, Hollander Z, Wilson-McManus J, Balshaw R, Ng RT, McMaster R, McManus BM, Keown PA, Tebbutt SJ. White blood cell differentials enrich whole blood expression data in the context of acute cardiac allograft rejection. Bioinform Biol Insights. 2012;6:49-61. doi: 10.4137/BBI.S9197. Epub 2012 Apr 10.
- Background: PubMed 21962426Lin D, Hollander Z, Meredith A, Stadnick E, Sasaki M, Cohen Freue G, Qasimi P, Mui A, Ng RT, Balshaw R, Wilson-McManus JE, Wishart D, Hau D, Keown PA, McMaster R, McManus BM; Biomarkers in Transplantation Team; NCE CECR PROOF Centre of Excellence. Molecular signatures of end-stage heart failure. J Card Fail. 2011 Oct;17(10):867-74. doi: 10.1016/j.cardfail.2011.07.001. Epub 2011 Sep 3.
- Background: PubMed 21076371Hollander Z, Lin D, Chen V, Ng R, Wilson-McManus J, Ignaszewski A, Cohen Freue G, Balshaw R, Mui A, McMaster R, Keown PA, McManus BM; NCE CECR PROOF Centre of Excellence. Whole blood biomarkers of acute cardiac allograft rejection: double-crossing the biopsy. Transplantation. 2010 Dec 27;90(12):1388-93. doi: 10.1097/TP.0b013e3182003df6.
- Background: PubMed 19716046Lin D, Hollander Z, Ng RT, Imai C, Ignaszewski A, Balshaw R, Freue GC, Wilson-McManus JE, Qasimi P, Meredith A, Mui A, Triche T, McMaster R, Keown PA, McManus BM; Biomarkers in Transplantation Team; NCE CECR Centre of Excellence for the Prevention of Organ Failure. Whole blood genomic biomarkers of acute cardiac allograft rejection. J Heart Lung Transplant. 2009 Sep;28(9):927-35. doi: 10.1016/j.healun.2009.04.025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott Tebbutt, PhD principal investigator
University of British Columbia
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Transplant Failure and Rejection and Heart Failure, run by University of British Columbia at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Canada, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03575910, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2026.