Cardiac FailureOPTIMALNCT06939751
OPtimal Adult Heart Transplant Immunosuppression With MicroRNA Levels
An observational study of Cardiac Failure and Graft Rejection, run by Northwestern University at 6 sites in United States.
Trial summary
This study aims to develop and refine a microRNA (miR) biomarker panel that can be used to phenotype net immune state after heart transplantation using circulating miRs (associated with drug doses and levels). Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Cardiac Failure, Graft Rejection
- How many people
- 250 participants
- Where
- 6 sitesUnited States
- Study dates
- 28 Oct 2025to 1 Jan 2032
- How long will I take part?
- 3 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients ≥ 18 years of age from geographically and socioeconomically diverse regions of the U.S who have undergone orthotopic heart transplant (OHT) Patients will be screened for eligibility and enrolled within ~ 1 month after heart transplant
Who may be able to join
- 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.
- Patient able and willing to comply with the study visit schedule, study procedures, and study requirements.
Who cannot join
- Recipient of a multi-organ transplant
- History of prior solid organ transplant before the index heart transplant
- Ongoing mechanical circulatory support or hemodynamic instability (e.g., inotrope or vasopressor therapy)
- Ongoing need for renal replacement therapy and/or dialysis
- Active infection requiring either a) hospitalization b) treatment with antimicrobial therapy or c) reduction in immunosuppression
- Active rejection being treated with intravenous medications or plasmapheresis
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
United States6 sites, 6 recruiting
- Recruiting
Tufts Medical Center
Boston, Massachusetts, 02111
Abena Adwetewa-Badu, 617-636-9458, Abena.Adwetewa-Badu@tuftsmedicine.org
Jeong Hwan Kim, MD
- Recruiting
Medical University of South Carolina
Charleston, South Carolina, 29425
Melissa Amitrano, amitrano@musc.edu
Ryan Tedford, MD
- Recruiting
Baylor University Medical Center
Dallas, Texas, 75246
Jasha Harvey, jasha.harvey@BSWHealth.org
Shelley Hall, MD
- Recruiting
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Lucilla Garcia, lucilla.garcia@csmns.org
Jon Kobashigawa, MD
- Recruiting
Vanderbilt University
Nashville, Tennessee, 37232
Lisa Slinger, Lisa.slinger@vumc.org
Kelly Schlendorf, MD
- Recruiting
Stanford University
Palo Alto, California, 94304
James Pak, jamespak@stanford.edu
Kiran Khush, MD
About this study
This study aims to develop and refine a microRNA (miR) biomarker panel that can be used to phenotype net immune state after heart transplantation using circulating miRs (associated with drug doses and levels). These miRs will be used to characterize the overall immune state in adult 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.
Read the detailed description
The study objectives will be accomplished in a prospective, multicenter observational, longitudinal cohort study that includes ~250 Heart Transplant patients from the United States. Patients will be screened for eligibility and enrolled ~1 month (± 2 weeks) after transplant. Study participation will last 36 months.
All patients will follow the center's standard of care surveillance schedule after transplant. Blood samples will be collected for miR evaluation at:
- specified time intervals after transplant and
- when a clinical event of interest occurs, including treated rejection, or infection.
Research samples will be collected and used to evaluate miR 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.
- Conditions
- Cardiac Failure, Graft Rejection
- Medical subject headings
- Heart Failure
What is being measured
The primary outcome is the main question the study is designed to answer.
Time-to-Event Analysis of Circulating microRNAs (miRs) Predicting Infection in Pediatric Heart Transplant Recipients
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
Measured: up to 3 years post - transplant
Time-to-Event Analysis of Circulating microRNAs (miRs) Predicting Rejection in Pediatric Heart Transplant Recipients
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.
Measured: up to 3 years post - transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2025
- Study start28 Oct 2025
- Primary completion1 Jan 2031 (estimated)
- Study completion1 Jan 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cardiac FailureStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe 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
- 250 participants (estimated)
- Target duration
- 3 Years
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Palak Shah, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06939751
- Sponsor's protocol ID
- Northwestern-2024-372
- Other IDs
- 1R01HL173248-01A1
- Acronym
- OPTIMAL
- Status last verified
- Aug 2026
- First submitted
- 15 Apr 2025
- Last updated
- 11 Aug 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Shah P, Bristow MR, Port JD. MicroRNAs in Heart Failure, Cardiac Transplantation, and Myocardial Recovery: Biomarkers with Therapeutic Potential. Curr Heart Fail Rep. 2017 Dec;14(6):454-464. doi: 10.1007/s11897-017-0362-8.
PubMed 28940102Shah P, Agbor-Enoh S, Bagchi P, deFilippi CR, Mercado A, Diao G, Morales DJ, Shah KB, Najjar SS, Feller E, Hsu S, Rodrigo ME, Lewsey SC, Jang MK, Marboe C, Berry GJ, Khush KK, Valantine HA; GRAfT Investigators. Circulating microRNAs in cellular and antibody-mediated heart transplant rejection. J Heart Lung Transplant. 2022 Oct;41(10):1401-1413. doi: 10.1016/j.healun.2022.06.019. Epub 2022 Jun 28.
PubMed 35872109
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- OPtimal Adult Heart Transplant Immunosuppression With MicroRNA Levels
- ClinicalTrials.gov ID
- NCT06939751
- Acronym / sponsor ID
- OPTIMAL / Northwestern-2024-372
- Conditions
- Cardiac Failure, Graft Rejection
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 28 Oct 2025 (actual)
- Primary completion
- 1 Jan 2031 (estimated)
- Study completion
- 1 Jan 2032 (estimated)
- First posted
- 23 Apr 2025 (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.
This study aims to develop and refine a microRNA (miR) biomarker panel that can be used to phenotype net immune state after heart transplantation using circulating miRs (associated with drug doses and levels). These miRs will be used to characterize the overall immune state in adult 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 ~250 Heart Transplant patients from the United States. Patients will be screened for eligibility and enrolled ~1 month (± 2 weeks) after transplant. Study participation will last 36 months.
All patients will follow the center's standard of care surveillance schedule after transplant. Blood samples will be collected for miR evaluation at:
- specified time intervals after transplant and
- when a clinical event of interest occurs, including treated rejection, or infection.
Research samples will be collected and used to evaluate miR 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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 3 Years
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients ≥ 18 years of age from geographically and socioeconomically diverse regions of the U.S who have undergone orthotopic heart transplant (OHT) Patients will be screened for eligibility and enrolled within ~ 1 month after heart transplant
Key inclusion criteria (4 listed)
- 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.
- Patient able and willing to comply with the study visit schedule, study procedures, and study requirements.
Key exclusion criteria (6 listed)
- Recipient of a multi-organ transplant
- History of prior solid organ transplant before the index heart transplant
- Ongoing mechanical circulatory support or hemodynamic instability (e.g., inotrope or vasopressor therapy)
- Ongoing need for renal replacement therapy and/or dialysis
- Active infection requiring either a) hospitalization b) treatment with antimicrobial therapy or c) reduction in immunosuppression
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
Time-to-Event Analysis of Circulating microRNAs (miRs) Predicting Infection in Pediatric Heart Transplant Recipients
Time frame: up to 3 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
Time-to-Event Analysis of Circulating microRNAs (miRs) Predicting Rejection in Pediatric Heart Transplant Recipients
Time frame: up to 3 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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2026.
- Background: PubMed 28940102Shah P, Bristow MR, Port JD. MicroRNAs in Heart Failure, Cardiac Transplantation, and Myocardial Recovery: Biomarkers with Therapeutic Potential. Curr Heart Fail Rep. 2017 Dec;14(6):454-464. doi: 10.1007/s11897-017-0362-8.
- Background: PubMed 35872109Shah P, Agbor-Enoh S, Bagchi P, deFilippi CR, Mercado A, Diao G, Morales DJ, Shah KB, Najjar SS, Feller E, Hsu S, Rodrigo ME, Lewsey SC, Jang MK, Marboe C, Berry GJ, Khush KK, Valantine HA; GRAfT Investigators. Circulating microRNAs in cellular and antibody-mediated heart transplant rejection. J Heart Lung Transplant. 2022 Oct;41(10):1401-1413. doi: 10.1016/j.healun.2022.06.019. Epub 2022 Jun 28.
- Individual participant dataSharing planned: No
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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.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiac Failure and Graft Rejection, run by Northwestern University at 6 sites in United States.
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 6 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: looking for participants now, as of the sponsor's last update on 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Palak Shah, MD (312-694-7805, optimal@northwestern.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time-to-Event Analysis of Circulating microRNAs (miRs) Predicting Infection in Pediatric Heart Transplant Recipients (time frame: up to 3 years post - transplant). The study lists 2 primary outcomes in all. 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 NCT06939751, which also lists 2 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 11 Aug 2026.