A New Biomarker for the Non-invasive Diagnosis of Rejection After Heart Transplantation
- Conditions
- Heart Transplant Rejection
- Interventions
- Diagnostic Test: donor-derived cell-free DNA (dd-cfDNA)
- Registration Number
- NCT03477383
- Lead Sponsor
- Vastra Gotaland Region
- Brief Summary
This study is a prospective, observational multi-center cohort study. The study will consist of patients undergoing heart transplantation. The main purpose is to test a new biomarker for rejection against the gold-standard, the endomyocardial biopsy (EMB). 80 patients will be included, both children and adults.
- Detailed Description
The primary objective is a comparison of an the established, invasive diagnostic test, the endomyocardial biopsy (EMB) against a new, non-invasive test. The new test is the measurement of donor-derived cell-free DNA (dd-cfDNA) circulating in the blood stream of the recipient, quantified by droplet digital PCR (polymerase-chain reaction) after targeted multiplex preamplification. Sensitivity is calculated with EMB as the gold standard. The patients will be followed during one year post-transplantation with simultaneous blood samples and EMB. The patients will further be followed clinically for 5 years. A suitable cut-off for the ratio of dd-cfDNA will be calculated using receiver operating characteristic (ROC) analysis.
Secondary objectives are description of patient outcomes with respect to organ function, quality of life and adverse events.
Secondary objectives are the calculation of the costs related to the transplantation process as well as to the follow-up with EMB. A simulation will be done with respect to possible savings achieved if the new biomarker could be implemented.
The study consists of two cohorts: all adult recipients of heart transplantation at Sahlgrenska University Hospital (one of two center conducting heart transplantation in Sweden): regional study. The other cohort consists of all children undergoing heart transplantation in Sweden:national study. Patients will undergo transplantation at Sahlgrenska University Hospital in Gothenburg as well as at Skåne University Hospital in Lund. Follow-up with blood samples and EMB of these patients will be in Gothenburg, Lund and at Karolinska University Hospital in Stockholm.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 134
- Patient on waiting list for heart transplantation
- Signed informed consent
- Follow-up outside Sweden
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Pediatric patients donor-derived cell-free DNA (dd-cfDNA) Pediatric patients (0-17 years) undergoing heart transplantation Adult patients donor-derived cell-free DNA (dd-cfDNA) Adult patients (18 years or older) undergoing heart transplantation
- Primary Outcome Measures
Name Time Method Comparison of donor-derived cell-free DNA and endomyocardial biopsy with respect to rejection 3 years Measurement of both fraction of donor-derived cell-free DNA of all cell-free DNA (derived from recipient and donor) as well as the absolute number of copies per ml plasma derived from the donor. Comparison is made with simultaneously obtained endomyocardial biopsies that are graded with respect to rejection, according to the official guidelines provided by the International Society of Heart and Lung Transplantation.
- Secondary Outcome Measures
Name Time Method Immunization status 5 years Impact of pre-transplantation immunization status on primary and secondary outcomes
Prior cardiac surgery 5 years Impact of prior cardiac surgery on other outcomes
Neonatal cardiac surgery 5 years Impact of neonatal (first 4 weeks of life) cardiac surgery on other outcomes
Rejection 5 years Cumulative incidence of rejection (according to the biopsy grading system provided by the International Society of Heart and Lung Transplantation)
Graft-vasculopathy 5 years Cumulative incidence of graft-vasculopathy
Quality of life 5 years Health-related quality of life as measured by EQ5D
GFR (glomerular filtration rate) 5 years Renal function evaluated by calculated and measured GFR (Iohexol or Cr-Clearance)
Donor cardiac arrest 5 years Correlation between circulatory arrest in the donor and cardiac function
Initial immunosuppression 5 years Correlation between initial immunosuppression and the incidence of rejection
Ischemia time 5 years Correlation between ischemic graft time and cardiac function as measured by echocardiography
Re-transplantation 5 years Proportion of patients who have undergone re-transplantation
Infections 5 years Cumulative incidence of infections requiring hospital admission
Donor cardiopulmonary resuscitation (CPR) impact 3 years Impact of CPR of the donor on the incidence of assumed early rejection
Immunosuppression and adverse effects 5 years Correlation of time points with over- or under-immunosuppression (as measured by blood levels of immunosuppressive drugs and comparison with desired levels) and the incidence of severe infection, renal function decline and malignancy
Immunosuppression and rejection 5 years Correlation of time points with over- or under-immunosuppression (as measured by blood levels of immunosuppressive drugs and comparison with desired levels) with rejection events
Blood products and adverse events 5 years Correlation between the number of blood products (red blood cells, thrombocytes, plasma) given after transplantation and the incidence of adverse effects
Overweight 5 years Prevalence of overweight (BMI \>25) and obesity (BMI\>30)
Circulatory support to transplantation 5 years Proportion of patients undergoing heart transplantation from a ventricular assist device or extra-corporeal membrane oxygenation (ECMO) or from mechanical ventilation.
Malignancy 5 years Cumulative incidence of malignancy (PTLD and others)
Initial immunosuppression and malignancy 5 years Correlation between type of initial immunosuppression and incidence of malignancy
Survival 3 years Survival
Cost analysis 1 5 years Costs of heart transplantation during the first year post-transplantation
Trial Locations
- Locations (4)
Pediatric Heart Center, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital
🇸🇪Gothenburg, Sweden
Pediatric Heart Center, Karolinska University Hospital
🇸🇪Stockholm, Sweden
Transplantation Center, Sahlgrenska University Hospital
🇸🇪Gothenburg, Sweden
Pediatric Heart Center, Skåne University Hospital
🇸🇪Lund, Sweden