Pediatric Heart TransplantationNCT02752789
Impact of Allo- and Autoantibodies on Chronic Cardiac Allograft Function
An observational study of Pediatric Heart Transplantation and Pediatric Heart Transplant Recipients, run by National Institute of Allergy and Infectious Diseases (NIAID) at 9 sites in 2 countries.
Trial summary
This is a multi-center, prospective, single cohort, observational study of pediatric heart transplant recipients designed to determine the impact of preformed versus de novo human leukocyte antigen (HLA) donor-specific antibodies (DSA), and antibodies to the self-antigens cardiac myosin and vimentin, on chronic… Read more about this study
- Who is it for?
- Ages Up to 20 years
- Conditions the study is for
- Pediatric Heart Transplantation, Pediatric Heart Transplant Recipients
- How many people
- 407 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 15 Jul 2014to 1 Nov 2019
- 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 Up to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Participants that were enrolled in CTOTC-04 (ClinicalTrials.gov ID NCT01005316) who consent to long-term follow-up and new participants at the nine designated sites who are listed for isolated orthotopic heart transplantation
Who may be able to join
- Subject and/or parent guardian able to understand and provide informed consent and where applicable assent
- Planned long-term follow-up at one of the study sites
- AND either:
- -Enrolled in the CTOTC-04 study and actively followed at one of the study sites
- OR
- -Listed at participating study sites, less than 21 years of age and not yet transplanted.
- The inclusion criteria for enrollment of new study patients in the CTOTC-09 Protocol will be the same as the CTOTC-04 study (refer to ClinicalTrials.gov ID NCT01005316).
Who cannot join
- Parental withdrawal of consent from the CTOTC-04 study
- Past or current medical problems or findings from physical examination or laboratory testing that, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or may impact the quality or interpretation of the data obtained from the study
- Listed for simultaneous multiple organ transplant.
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
United States8 sites
Emory University School of Medicine
Atlanta, Georgia, 30060
Children's Hospital Boston
Boston, Massachusetts, 02115
Monroe Carell Jr. Children's Hospital
Nashville, Tennessee, 37232
Columbia University Medical Center
New York, New York, 10032
Children's Hospital at Montefiore
New York, New York, 10467
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
St. Louis Children's Hospital
St Louis, Missouri, 63110
About this study
Official title: An Observational Cohort Study to Determine the Impact of Alloantibodies and Antibodies to Self Antigens on Chronic Graft Function up to 5 Years After Pediatric Heart Transplantation (CTOTC-09)
This is a multi-center, prospective, single cohort, observational study of pediatric heart transplant recipients designed to determine the impact of preformed versus de novo human leukocyte antigen (HLA) donor-specific antibodies (DSA), and antibodies to the self-antigens cardiac myosin and vimentin, on chronic allograft function. In addition, the investigators will explore mechanisms of action and predictors of DSA, rejection and altered pathophysiology.
Read the detailed description
Participants that were enrolled in the CTOTC-04 study (ClinicalTrials.gov Identifier NCT01005316) are invited to enroll in this CTOTC-09 study. Conversion from the CTOTC-04 to CTOTC-09 study will occur in such a manner as to avoid/minimize discontinuity of follow-up between the planned CTOTC-04 and CTOTC-09 study visits. In addition, subjects added to the United Network for Organ Sharing (UNOS) system-or Canadian equivalent agency-at a participating study site, who are less than 21 years of age and fulfill all study eligibility criteria, will be invited to enroll in CTOTC-09.
This study focuses on the importance of antibodies against the newly transplanted heart in pediatric heart transplant recipients. The investigators aim to determine if certain antibodies lead to problems with the heart transplant. Antibodies are small proteins in the blood that the body makes to fight off infections, for example with bacteria or viruses. Since a new heart is "foreign" to the recipient's body, their immune system might try to attack it with antibodies, as if it were an infection. For many years it was thought that only white blood cells attacked the new heart, causing rejection.
Now there is new information showing that antibodies may also cause rejection or long-term damage to the heart. At this time, very little is known about how antibodies might cause problems after heart transplantation in transplant recipients younger than 21 years at the time of transplant.
This study will collect a medical history and blood samples at specified times for research. The blood samples will be used to measure antibodies in the blood, and to perform special tests to see how these antibodies might damage the heart.
Participant follow-up is from the day of the heart transplant to year 5 post-transplant.
- Keywords
- alloantibodies, donor specific antibodies (DSA)-preformed, de novo, self-antigens, chronic allograft function
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 |
|---|---|---|
| Pediatric Heart Transplant Recipients | CTOTC-04 (ClinicalTrials.gov ID NCT01005316) participants who consent to long-term follow-up as part of this study as well as candidates less than 21 years of age who are listed for isolated orthotopic heart transplantation at one of the participating sites |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pulmonary capillary wedge pressure at heart catheterization
Measured: 3 years post-transplantation
Secondary outcomes (16)
Other invasive cardiac hemodynamic findings at cardiac catheterization
Cardiac hemodynamic findings: right and left ventricular end diastolic pressures, right atrial pressure, pulmonary artery pressure and cardiac index
Measured: 3 and 5 years post-transplantation
Frequency of development of post-transplant de novo DSA and autoantibodies to cardiac myosin and vimentin
Measured: 3 years post-transplantation
Time course of development of post-transplant de novo DSA and autoantibodies to cardiac myosin and vimentin.
Measured: 3 years post-transplantation
Frequency of first episode of late acute rejection
Measured: From >1 year to 5 years post-transplantation
Time to first episode of late acute rejection
Late acute rejection is defined as occurring >1 year post-transplantation
Measured: From >1 year to 5 years post-transplantation
Frequency to recurrent (two or more) late acute rejections
Measured: Up to 5 years post-transplantation
Time to recurrent late acute rejections
Recurrent defined as two or more late acute rejection episodes
Measured: Up to 5 years post-transplantation
Frequency to first episode of late acute rejection with hemodynamic compromise
Measured: Up to 5 years post-transplantation
Time to first episode of late acute rejection with hemodynamic compromise
Measured: Up to 5 years post-transplantation
Time to graft loss (death or retransplantation) conditional to surviving one year post-transplantation
Measured: One year and up to 5 years post-transplantation
N-terminal pro-brain Natriuretic Peptide (NT-proBNP)/Brain Natriuretic Peptide (BNP)
Measured: 3 and 5 years post-transplantation
Systolic and diastolic graft function
Graft function as assessed by echocardiography
Measured: 3 and 5 years
Proportion of participants with angiographic evidence of coronary artery disease
Measured: 3 and 5 years post-transplantation
Time to graft loss (death or retransplantation) after first late rejection
Measured: Up to 5 years post-transplantation
Medication Adherence Measure (MAM) after hospital discharge
Measured: Up to 5 years post-transplantation
Variability of maintenance tacrolimus levels
Measured: Up to 5 years post-transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2016 (estimated)
- Study start15 Jul 2014
- Primary completion1 Nov 2019
- Study completion1 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pediatric Heart TransplantationStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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
- 407 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Clinical Trials in Organ Transplantation in Children
- Responsible party
- Sponsor
- Investigators
- Steven A. Webber, MBChB, MRCP, Study chair, Monroe Carell Jr. Children's Hospital at Vanderbilt: Pediatric TransplantationSteven A. Webber, MBChB, MRCP, Principal investigator, Monroe Carell Jr. Children's Hospital at Vanderbilt: Pediatric Transplantation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02752789
- Sponsor's protocol ID
- DAIT CTOTC-09
- Status last verified
- Nov 2019
- First submitted
- 22 Apr 2016
- Last updated
- 29 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Observational Cohort Study to Determine the Impact of Alloantibodies and Antibodies to Self Antigens on Chronic Graft Function up to 5 Years After Pediatric Heart Transplantation (CTOTC-09)
- ClinicalTrials.gov ID
- NCT02752789
- Acronym / sponsor ID
- DAIT CTOTC-09
- Keywords
- alloantibodies, donor specific antibodies (DSA)-preformed, de novo, self-antigens, chronic allograft function
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 407 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Clinical Trials in Organ Transplantation in Children
- Study start
- 15 Jul 2014 (actual)
- Primary completion
- 1 Nov 2019 (actual)
- Study completion
- 1 Nov 2019 (actual)
- First posted
- 27 Apr 2016 (estimated)
- 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 is a multi-center, prospective, single cohort, observational study of pediatric heart transplant recipients designed to determine the impact of preformed versus de novo human leukocyte antigen (HLA) donor-specific antibodies (DSA), and antibodies to the self-antigens cardiac myosin and vimentin, on chronic allograft function. In addition, the investigators will explore mechanisms of action and predictors of DSA, rejection and altered pathophysiology.
Detailed description
Participants that were enrolled in the CTOTC-04 study (ClinicalTrials.gov Identifier NCT01005316) are invited to enroll in this CTOTC-09 study. Conversion from the CTOTC-04 to CTOTC-09 study will occur in such a manner as to avoid/minimize discontinuity of follow-up between the planned CTOTC-04 and CTOTC-09 study visits. In addition, subjects added to the United Network for Organ Sharing (UNOS) system-or Canadian equivalent agency-at a participating study site, who are less than 21 years of age and fulfill all study eligibility criteria, will be invited to enroll in CTOTC-09.
This study focuses on the importance of antibodies against the newly transplanted heart in pediatric heart transplant recipients. The investigators aim to determine if certain antibodies lead to problems with the heart transplant. Antibodies are small proteins in the blood that the body makes to fight off infections, for example with bacteria or viruses. Since a new heart is "foreign" to the recipient's body, their immune system might try to attack it with antibodies, as if it were an infection. For many years it was thought that only white blood cells attacked the new heart, causing rejection.
Now there is new information showing that antibodies may also cause rejection or long-term damage to the heart. At this time, very little is known about how antibodies might cause problems after heart transplantation in transplant recipients younger than 21 years at the time of transplant.
This study will collect a medical history and blood samples at specified times for research. The blood samples will be used to measure antibodies in the blood, and to perform special tests to see how these antibodies might damage the heart.
Participant follow-up is from the day of the heart transplant to year 5 post-transplant.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pediatric Heart Transplant Recipients | – | –CTOTC-04 (ClinicalTrials.gov ID NCT01005316) participants who consent to long-term follow-up as part of this study as well as candidates less than 21 years of age who are listed for isolated orthotopic heart transplantation at one of the participating sites |
Who may qualify
- Ages
- Up to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Participants that were enrolled in CTOTC-04 (ClinicalTrials.gov ID NCT01005316) who consent to long-term follow-up and new participants at the nine designated sites who are listed for isolated orthotopic heart transplantation
Key inclusion criteria (7 listed)
- Subject and/or parent guardian able to understand and provide informed consent and where applicable assent
- Planned long-term follow-up at one of the study sites
- -Enrolled in the CTOTC-04 study and actively followed at one of the study sites
- OR
- -Listed at participating study sites, less than 21 years of age and not yet transplanted.
Key exclusion criteria (3 listed)
- Parental withdrawal of consent from the CTOTC-04 study
- Past or current medical problems or findings from physical examination or laboratory testing that, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or may impact the quality or interpretation of the data obtained from the study
- Listed for simultaneous multiple organ transplant.
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
Pulmonary capillary wedge pressure at heart catheterization
Time frame: 3 years post-transplantation
16 secondary outcomes
Other invasive cardiac hemodynamic findings at cardiac catheterization
Time frame: 3 and 5 years post-transplantation
Frequency of development of post-transplant de novo DSA and autoantibodies to cardiac myosin and vimentin
Time frame: 3 years post-transplantation
Time course of development of post-transplant de novo DSA and autoantibodies to cardiac myosin and vimentin.
Time frame: 3 years post-transplantation
Frequency of first episode of late acute rejection
Time frame: From >1 year to 5 years post-transplantation
Time to first episode of late acute rejection
Time frame: From >1 year to 5 years post-transplantation
Frequency to recurrent (two or more) late acute rejections
Time frame: Up to 5 years post-transplantation
Time to recurrent late acute rejections
Time frame: Up to 5 years post-transplantation
Frequency to first episode of late acute rejection with hemodynamic compromise
Time frame: Up to 5 years post-transplantation
Time to first episode of late acute rejection with hemodynamic compromise
Time frame: Up to 5 years post-transplantation
Time to graft loss (death or retransplantation) conditional to surviving one year post-transplantation
Time frame: One year and up to 5 years post-transplantation
N-terminal pro-brain Natriuretic Peptide (NT-proBNP)/Brain Natriuretic Peptide (BNP)
Time frame: 3 and 5 years post-transplantation
Systolic and diastolic graft function
Time frame: 3 and 5 years
Proportion of participants with angiographic evidence of coronary artery disease
Time frame: 3 and 5 years post-transplantation
Time to graft loss (death or retransplantation) after first late rejection
Time frame: Up to 5 years post-transplantation
Medication Adherence Measure (MAM) after hospital discharge
Time frame: Up to 5 years post-transplantation
Variability of maintenance tacrolimus levels
Time frame: Up to 5 years post-transplantation
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 29 Nov 2019.
- National Institute of Allergy and Infectious Diseases (NIAID)Link provided by the sponsor.
- Division of Allergy, Immunology, and Transplantation (DAIT)Link provided by the sponsor.
- Clinical Trials in Organ Transplantation in Children (CTOT-C)Link provided by the sponsor.
Related trials for Pediatric Heart Transplantation
Not yet recruiting
Autologous Thymus Transplant in Children With Congenital Heart Disease: A Pilot Study
Congenital Heart Disease (CHD)
Enrolling by invitation
EXCOR Active Driving System for the EXCOR Pediatric VAD IDE Study
Heart Failure, Transplant; Failure, Heart
RecruitingObservational study
Determine the Prevalence of Exocrine Pancreatic Insufficiency (EPI) in Pediatric and Adult Participants With Alagille Syndrome After Liver Transplantation
Exocrine Pancreatic Insuficiency
Not yet recruiting
TORCH-LATAM-003: Regional Advanced-Therapy Pathways for Congenital Heart Disease
Congenital Heart Disease, Advanced Heart Failure
Not yet recruiting
TORCH-LATAM: A Regional Pathway to Improve Transplant Evaluation for Congenital Heart Disease
Congenital Heart Disease
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.
Steven A. Webber, MBChB, MRCP study chair
Monroe Carell Jr. Children's Hospital at Vanderbilt: Pediatric Transplantation
Steven A. Webber, MBChB, MRCP principal investigator
Monroe Carell Jr. Children's Hospital at Vanderbilt: Pediatric Transplantation
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pediatric Heart Transplantation and Pediatric Heart Transplant Recipients, run by National Institute of Allergy and Infectious Diseases (NIAID) at 9 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 7 inclusion and 3 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 29 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Canada. 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?
Pulmonary capillary wedge pressure at heart catheterization (time frame: 3 years post-transplantation). 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 29 Nov 2019.