Congenital Heart DiseaseNCT06642662
Precision Medicine in the CICU: Identifying Proteomic Biomarkers
An observational study of Congenital Heart Disease, run by Boston Children's Hospital at 1 site in United States.
Trial summary
Congenital Heart disease (CHD) is a leading cause of childhood death. Substantial morbidity and mortality relates to the postoperative course. For example, only 70% of neonates survive to hospital discharge after their first complex surgery for single ventricle heart disease. Read more about this study
- Who is it for?
- Ages 2 days to 5 years
- Conditions the study is for
- Congenital Heart Disease
- What is being tested?
- Somascan 5.0
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Apr 2025to 15 Apr 2027
- How long will I take part?
- 3 Weeks
- 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 2 days to 5 years
- All sexes
- No healthy volunteers
- Child
Study population: Prospective patients undergoing S1P for HLHS, BiV repair, or ASO will be identified. Inclusion: elective BiV repair in patients aged >1 and <5 years or standard risk S1P/ASO. Exclusion: preoperative ventilation or vasoactive support. With primary treating team approval, the investigators will approach parents of eligible patients to discuss study participation with written informed consent obtained if they agree to enroll.
Who may be able to join
- consent from parents
- cardiac surgical criteria and age criteria; elective BiV repair in patients aged >1 and <5 years or standard risk S1P/ASO
Who cannot join
- preoperative ventilation or vasoactive support or ECMO
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Boston Children's Hospital
Boston, Massachusetts, 02115
About this study
Official title: Exploring Precision Medicine in the CICU: Feasibility of Proteomic Biomarkers
Congenital Heart disease (CHD) is a leading cause of childhood death. Substantial morbidity and mortality relates to the postoperative course. For example, only 70% of neonates survive to hospital discharge after their first complex surgery for single ventricle heart disease. Adverse systemic inflammatory responses are highly exaggerated in some children postoperatively. This inflammation is pathological, results in leaky blood vessels and fluid overload, toxin release as well as cell damage contributing to lung, heart and kidney injury. Reasons why some children develop this amplified systemic inflammatory response after heart surgery while others do not are poorly understood. Mechanisms for how cardiopulmonary bypass and surgery drive this inflammation are also inadequately characterized. Currently, there are no existing methods to predict patients at high-risk for acute adverse postoperative complications, let alone adjust our management to mitigate these effects. Instead, our postoperative care approach is a one-size fits all, reactive process 'after' patients become inflamed or adverse events occur.
Proteins in a patient's blood participate in and reflect acute inflammatory responses. In other pediatric conditions, protein biomarkers have been shown to both predict and monitor inflammation and adverse outcomes, and importantly predict responsiveness to anti-inflammatory drug therapies. This is the premise of precision medicine. Personalizing treatment to each individual patient.
Read more
New technologies now allow the levels of tens of thousands of proteins to be measured from a few drops of blood. In this proposal the investigators will identify predictors of adverse events after heart surgery by quantifying protein levels and their changes after surgery. It is now possible to detect those proteins with the greatest variability in the postoperative course over time, and between patients, as well as those that are associated with adverse outcomes. The most informative proteins will yield insights into the causes of the inflammatory response. The investigators anticipate identifying protein plasma biomarkers in pathways associated with inflammation, metabolism, blood vessel function and the immune system as these may be key mechanisms involved. Advanced understanding of these mechanisms is critical to deriving targeted therapies to prevent or mitigate inflammatory responses.
The investigators will also collect patient clinical data, such as age, cardiac anatomy, and duration of surgery. By combining this clinical information with blood protein profiles, the investigators will be able to develop a model predicting patients at highest risk for adverse postoperative events using machine learning approaches. The overarching goal of this research integrating clinical and bench research is ultimately to translate precision medicine approaches to the Cardiac ICU. Guiding personalized care of high-risk patients by enabling clinicians to anticipate outcomes and tailor decision-making at the bedside will undoubtably improve outcomes in CHD.
Read the detailed description
Acute inflammation following cardiopulmonary bypass (CPB) contributes to morbidity and mortality; however, mechanisms eliciting these responses and biomarkers predicting at-risk patients remain unidentified. Proteins are disease-associated circulating factors in patients' blood that both participate in and reflect inflammation. Existing data suggests proteomic biomarkers hold promise for predicting and monitoring inflammation and adverse outcomes; however, further research is needed to validate biomarkers in pediatric cardiac disease, elucidate underlying mechanisms of CPB-induced inflammation, and translate them to clinical practice.
Specific Aims: Our overarching goal is to integrate quantitative biomarkers with clinical medicine to enhance care of patients with congenital heart disease (CHD) by personalizing their treatment. The investigators propose a first step towards a precision medicine paradigm for children with CHD, many of whom experience inflammation post-CPB. The investigators hypothesize that proteomic profiling will detect biomarkers that identify patients at highest risk for exaggerated systemic inflammatory responses to CPB. The investigators will conduct a pilot feasibility study integrating unbiased proteome-wide discovery approaches, to offer a deep and unbiased view of the proteomic landscape underlying pathological processes post-CPB (Fig. 1).
AIM 1: To prospectively enroll patients with CHD undergoing CPB in a study of quantitative proteomic profiles.
Hypothesis: Conducting an observational study utilizing unbiased proteome-wide discovery approaches in children in the cardiac intensive care unit (CICU) undergoing CPB is feasible. The investigators will identify 80 children in 3 diagnosis cohorts. Those undergoing stage 1 palliation (S1P) for hypoplastic left heart syndrome (HLHS), or biventricular (BiV) repair both have elevated risk of exaggerated inflammatory responses with postoperative courses characterized by fluid overload, prolonged mechanical ventilation, fevers, and capillary leak, and those with D-transposition of the great arteries (DTGA) post arterial switch operation (ASO) have lower risk. The investigators will collect demographic and clinical data and obtain blood samples at four time points: pre-CPB, immediately post-CPB, 12 hrs post-CPB, and 24 hrs post-CPB. Plasma will be analyzed on the SomaScan v5.0 platform, which measures 10,778 proteins from a 55 µL plasma sample.
AIM 2: To enhance understanding of inflammatory responses in children undergoing CPB by characterizing proteomic changes. Hypothesis: Temporal intra-patient proteomic responses to CPB and their relationships with outcomes will be characterized by the SomaScan platform. The investigators will describe dynamic intra-patient temporal variability in protein levels from pre- to post-CPB. Next, the investigators will identify proteins that demonstrate the greatest variability between patients overall, across timepoints, and between patients, stratified by outcome. To discriminate candidate biomarkers of postoperative inflammation and adverse outcomes, the investigators will study three clinical endpoints: time to successful extubation, extent of fluid overload in the 72 hours post-CPB, and a composite binary adverse outcome. The biomarker search will be unbiased and broad, with control for false discovery. Predictive proteins will be validated by targeted multiplex immunoassay and pathways described using systems biology approaches.
AIM 3: To develop a machine learning classifier predicting patient outcomes based on proteomic profiles and clinical variables. Hypothesis: Adverse outcomes following CPB will be predicted by a combination of clinical and proteomic biomarkers. The investigators will use supervised machine learning classifier approaches to discriminate and define the combination of proteomic and peri-operative clinical features (e.g. age, cardiac morphology/surgery, CPB, and circulatory arrest times) that accurately differentiate individuals at high risk of acute post-operative adverse events.
- Conditions
- Congenital Heart Disease
- Being tested
- Somascan 5.0
- Keywords
- proteomic, pediatric cardiac surgery, cardiopulmonary bypass
- Medical subject headings
- Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Somascan 5.0Diagnostic test
This observational study will test patient plasma using the SomaScan platform, a highly multiplexed proteomic tool that uses SOMAmers (Slow Off-rate Modified Aptamers) to bind with high specificity and affinity to preselected proteins to quantify levels. SomaScan v5.0 quantifies 10,778 clinically relevant human proteins, with several thousand proteins linked to inflammation and immune system functions, across a wide range of concentrations (>10 logs) with high sensitivity (<1 pg/mL) and reproducibility (median coefficient of variation < 5%). Individual protein concentrations are transformed into a corresponding SOMAmer concentration and quantified using a DNA microarray read-out.
| Study group | Role | What they receive |
|---|---|---|
| DTGA ASO | D-transposition of the great arteries (DTGA) post arterial switch operation (ASO) Receives: Diagnostic Test: Somascan 5.0 | |
| S1P | Neonates undergoing stage 1 palliation (S1P) for hypoplastic left heart syndrome (HLHS) Receives: Diagnostic Test: Somascan 5.0 | |
| BiV | Prior single ventricle palliation now undergoing biventricular (BiV) repair Receives: Diagnostic Test: Somascan 5.0 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time in hours to successful extubation
Time to successful extubation in hours
Measured: through ICU admission, average 1 week
Secondary outcomes (2)
Extent of fluid overload
Extent of cumulative fluid overload in the 72 hours post-bypass represented as a proportion of fluid balance by body weight
Measured: 3 days
Composite adverse outcome
The proportion meeting a composite binary adverse outcome; ie the proportion with a cardiac arrest, mechanical support, organ failure, or death within 7 days of surgery.
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2024
- Study start15 Apr 2025
- Primary completion1 Dec 2026 (estimated)
- Study completion15 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Congenital Heart DiseaseStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe 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
- 60 participants (estimated)
- Target duration
- 3 Weeks
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Katie Moynihan, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06642662
- Sponsor's protocol ID
- IRB-P00049754
- Status last verified
- Mar 2026
- First submitted
- 9 Oct 2024
- Last updated
- 2 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided: The investigators may share deidentified high dimensional proteomics data with the broader scientific and clinical community.
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploring Precision Medicine in the CICU: Feasibility of Proteomic Biomarkers
- ClinicalTrials.gov ID
- NCT06642662
- Acronym / sponsor ID
- IRB-P00049754
- Conditions
- Congenital Heart Disease
- Keywords
- proteomic, pediatric cardiac surgery, cardiopulmonary bypass
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Study start
- 15 Apr 2025 (actual)
- Primary completion
- 1 Dec 2026 (estimated)
- Study completion
- 15 Apr 2027 (estimated)
- First posted
- 15 Oct 2024 (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.
Congenital Heart disease (CHD) is a leading cause of childhood death. Substantial morbidity and mortality relates to the postoperative course. For example, only 70% of neonates survive to hospital discharge after their first complex surgery for single ventricle heart disease. Adverse systemic inflammatory responses are highly exaggerated in some children postoperatively. This inflammation is pathological, results in leaky blood vessels and fluid overload, toxin release as well as cell damage contributing to lung, heart and kidney injury. Reasons why some children develop this amplified systemic inflammatory response after heart surgery while others do not are poorly understood. Mechanisms for how cardiopulmonary bypass and surgery drive this inflammation are also inadequately characterized. Currently, there are no existing methods to predict patients at high-risk for acute adverse postoperative complications, let alone adjust our management to mitigate these effects. Instead, our postoperative care approach is a one-size fits all, reactive process 'after' patients become inflamed or adverse events occur.
Proteins in a patient's blood participate in and reflect acute inflammatory responses. In other pediatric conditions, protein biomarkers have been shown to both predict and monitor inflammation and adverse outcomes, and importantly predict responsiveness to anti-inflammatory drug therapies. This is the premise of precision medicine. Personalizing treatment to each individual patient.
New technologies now allow the levels of tens of thousands of proteins to be measured from a few drops of blood. In this proposal the investigators will identify predictors of adverse events after heart surgery by quantifying protein levels and their changes after surgery. It is now possible to detect those proteins with the greatest variability in the postoperative course over time, and between patients, as well as those that are associated with adverse outcomes. The most informative proteins will yield insights into the causes of the inflammatory response. The investigators anticipate identifying protein plasma biomarkers in pathways associated with inflammation, metabolism, blood vessel function and the immune system as these may be key mechanisms involved. Advanced understanding of these mechanisms is critical to deriving targeted therapies to prevent or mitigate inflammatory responses.
The investigators will also collect patient clinical data, such as age, cardiac anatomy, and duration of surgery. By combining this clinical information with blood protein profiles, the investigators will be able to develop a model predicting patients at highest risk for adverse postoperative events using machine learning approaches. The overarching goal of this research integrating clinical and bench research is ultimately to translate precision medicine approaches to the Cardiac ICU. Guiding personalized care of high-risk patients by enabling clinicians to anticipate outcomes and tailor decision-making at the bedside will undoubtably improve outcomes in CHD.
Detailed description
Acute inflammation following cardiopulmonary bypass (CPB) contributes to morbidity and mortality; however, mechanisms eliciting these responses and biomarkers predicting at-risk patients remain unidentified. Proteins are disease-associated circulating factors in patients' blood that both participate in and reflect inflammation. Existing data suggests proteomic biomarkers hold promise for predicting and monitoring inflammation and adverse outcomes; however, further research is needed to validate biomarkers in pediatric cardiac disease, elucidate underlying mechanisms of CPB-induced inflammation, and translate them to clinical practice.
Specific Aims: Our overarching goal is to integrate quantitative biomarkers with clinical medicine to enhance care of patients with congenital heart disease (CHD) by personalizing their treatment. The investigators propose a first step towards a precision medicine paradigm for children with CHD, many of whom experience inflammation post-CPB. The investigators hypothesize that proteomic profiling will detect biomarkers that identify patients at highest risk for exaggerated systemic inflammatory responses to CPB. The investigators will conduct a pilot feasibility study integrating unbiased proteome-wide discovery approaches, to offer a deep and unbiased view of the proteomic landscape underlying pathological processes post-CPB (Fig. 1).
AIM 1: To prospectively enroll patients with CHD undergoing CPB in a study of quantitative proteomic profiles.
Hypothesis: Conducting an observational study utilizing unbiased proteome-wide discovery approaches in children in the cardiac intensive care unit (CICU) undergoing CPB is feasible. The investigators will identify 80 children in 3 diagnosis cohorts. Those undergoing stage 1 palliation (S1P) for hypoplastic left heart syndrome (HLHS), or biventricular (BiV) repair both have elevated risk of exaggerated inflammatory responses with postoperative courses characterized by fluid overload, prolonged mechanical ventilation, fevers, and capillary leak, and those with D-transposition of the great arteries (DTGA) post arterial switch operation (ASO) have lower risk. The investigators will collect demographic and clinical data and obtain blood samples at four time points: pre-CPB, immediately post-CPB, 12 hrs post-CPB, and 24 hrs post-CPB. Plasma will be analyzed on the SomaScan v5.0 platform, which measures 10,778 proteins from a 55 µL plasma sample.
AIM 2: To enhance understanding of inflammatory responses in children undergoing CPB by characterizing proteomic changes. Hypothesis: Temporal intra-patient proteomic responses to CPB and their relationships with outcomes will be characterized by the SomaScan platform. The investigators will describe dynamic intra-patient temporal variability in protein levels from pre- to post-CPB. Next, the investigators will identify proteins that demonstrate the greatest variability between patients overall, across timepoints, and between patients, stratified by outcome. To discriminate candidate biomarkers of postoperative inflammation and adverse outcomes, the investigators will study three clinical endpoints: time to successful extubation, extent of fluid overload in the 72 hours post-CPB, and a composite binary adverse outcome. The biomarker search will be unbiased and broad, with control for false discovery. Predictive proteins will be validated by targeted multiplex immunoassay and pathways described using systems biology approaches.
AIM 3: To develop a machine learning classifier predicting patient outcomes based on proteomic profiles and clinical variables. Hypothesis: Adverse outcomes following CPB will be predicted by a combination of clinical and proteomic biomarkers. The investigators will use supervised machine learning classifier approaches to discriminate and define the combination of proteomic and peri-operative clinical features (e.g. age, cardiac morphology/surgery, CPB, and circulatory arrest times) that accurately differentiate individuals at high risk of acute post-operative adverse events.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 3 Weeks
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| DTGA ASO | – | Diagnostic Test: Somascan 5.0D-transposition of the great arteries (DTGA) post arterial switch operation (ASO) |
| S1P | – | Diagnostic Test: Somascan 5.0Neonates undergoing stage 1 palliation (S1P) for hypoplastic left heart syndrome (HLHS) |
| BiV | – | Diagnostic Test: Somascan 5.0Prior single ventricle palliation now undergoing biventricular (BiV) repair |
Who may qualify
- Ages
- 2 days to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Prospective patients undergoing S1P for HLHS, BiV repair, or ASO will be identified. Inclusion: elective BiV repair in patients aged >1 and <5 years or standard risk S1P/ASO. Exclusion: preoperative ventilation or vasoactive support. With primary treating team approval, the investigators will approach parents of eligible patients to discuss study participation with written informed consent obtained if they agree to enroll.
Key inclusion criteria (2 listed)
- consent from parents
- cardiac surgical criteria and age criteria; elective BiV repair in patients aged >1 and <5 years or standard risk S1P/ASO
Key exclusion criteria (1 listed)
- preoperative ventilation or vasoactive support or ECMO
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Somascan 5.0This observational study will test patient plasma using the SomaScan platform, a highly multiplexed proteomic tool that uses SOMAmers (Slow Off-rate Modified Aptamers) to bind with high specificity and affinity to preselected proteins to quantify levels. SomaScan v5.0 quantifies 10,778 clinically relevant human proteins, with several thousand proteins linked to inflammation and immune system functions, across a wide range of concentrations (>10 logs) with high sensitivity (<1 pg/mL) and reproducibility (median coefficient of variation < 5%). Individual protein concentrations are transformed into a corresponding SOMAmer concentration and quantified using a DNA microarray read-out. | Diagnostic test | BiV, DTGA ASO, S1P |
Primary outcome
Time in hours to successful extubation
Time frame: through ICU admission, average 1 week
Time to successful extubation in hours
2 secondary outcomes
Extent of fluid overload
Time frame: 3 days
Composite adverse outcome
Time frame: 7 days
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 2 Apr 2026.
- Individual participant dataSharing planned: Undecided. The investigators may share deidentified high dimensional proteomics data with the broader scientific and clinical community.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Congenital Heart Disease, run by Boston Children's Hospital at 1 site 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 2 inclusion and 1 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: enrolling by invitation, as of the sponsor's last update on 2 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
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?
Time in hours to successful extubation (time frame: through ICU admission, average 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Apr 2026.