Clinical trial NCT03477383: A New Biomarker for the Non-invasive Diagnosis of Rejection After Heart Transplantation
Official title: A New Biomarker for the Non-invasive Diagnosis of Rejection After Heart Transplantation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Transplant Rejection
Keywords: diagnosis
economics
cell-free DNA
digital droplet PCR
heart failure
Lead sponsor: Vastra Gotaland Region
Sponsor class: OTHER_GOV
Collaborators: name: Lund University Hospital
name: Karolinska University Hospital
First posted: 2018-03-26
Enrollment: 134
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients on waiting list for heart transplantion at the participating centers

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.

Eligibility criteria: Inclusion Criteria:

1. Patient on waiting list for heart transplantation
2. Signed informed consent

Exclusion Criteria:

1. Follow-up outside Sweden

Primary outcomes:
measure: Comparison of donor-derived cell-free DNA and endomyocardial biopsy with respect to rejection
timeFrame: 3 years
Secondary outcomes:
measure: Cost analysis 1
timeFrame: 5 years
measure: Rejection
timeFrame: 5 years
measure: Graft-vasculopathy
timeFrame: 5 years
measure: Overweight
timeFrame: 5 years
measure: Quality of life
timeFrame: 5 years
measure: Survival
timeFrame: 5 years
measure: Re-transplantation
timeFrame: 5 years
measure: GFR (glomerular filtration rate)
timeFrame: 1 year
measure: GFR (glomerular filtration rate)
timeFrame: 3 years
measure: GFR (glomerular filtration rate)
timeFrame: 5 years
measure: Infections
timeFrame: 5 years
measure: Circulatory support to transplantation
timeFrame: 5 years
measure: Immunization status
timeFrame: 5 years
measure: Malignancy
timeFrame: 3 years
measure: Malignancy
timeFrame: 5 years
measure: Prior cardiac surgery
timeFrame: 5 years
measure: Neonatal cardiac surgery
timeFrame: 5 years
measure: Donor cardiac arrest
timeFrame: 5 years
measure: Donor cardiopulmonary resuscitation (CPR) impact
timeFrame: 3 years
measure: Initial immunosuppression
timeFrame: 5 years
measure: Initial immunosuppression and malignancy
timeFrame: 5 years
measure: Immunosuppression and adverse effects
timeFrame: 5 years
measure: Immunosuppression and rejection
timeFrame: 5 years
measure: Ischemia time
timeFrame: 5 years
measure: Blood products and adverse events
timeFrame: 5 years
measure: Survival
timeFrame: 3 years
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Transplantation Center, Sahlgrenska University Hospital
city: Gothenburg
country: Sweden
facility: Pediatric Heart Center, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital
city: Lund
country: Sweden
facility: Pediatric Heart Center, Skåne University Hospital
city: Stockholm
country: Sweden
facility: Pediatric Heart Center, Karolinska University Hospital
Study officials:
affiliation: Pediatric Heart Center, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital
name: Jan Sunnegårdh, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: