A New Biomarker for the Non-invasive Diagnosis of Rejection After Heart Transplantation

Heart Transplant Rejection Clinical Trial

— BIODRAFT  

Official title:

A New Biomarker for the Non-invasive Diagnosis of Rejection After Heart Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03477383
• Other study ID #: ver 1.0
• Secondary ID: 014-16
• Status: Completed
• Start date: March 1, 2016
• Est. completion date: December 31, 2021

Study information

• Verified date: October 2021
• Source: Vastra Gotaland Region
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 134
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

1. Patient on waiting list for heart transplantation

2. Signed informed consent

Exclusion Criteria:

1. Follow-up outside Sweden

Related Conditions & MeSH terms

• Heart Transplant Rejection

Intervention

Diagnostic Test:
• donor-derived cell-free DNA (dd-cfDNA)
Measurement of dd-cfDNA and comparison against grade of rejection as measured by endomyocardial biopsy, taken simultaneously

Locations

Country	Name	City	State
Sweden	Pediatric Heart Center, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital	Gothenburg
Sweden	Transplantation Center, Sahlgrenska University Hospital	Gothenburg
Sweden	Pediatric Heart Center, Skåne University Hospital	Lund
Sweden	Pediatric Heart Center, Karolinska University Hospital	Stockholm

Sponsors (3)

Lead Sponsor	Collaborator
Vastra Gotaland Region	Karolinska University Hospital, Lund University Hospital

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of donor-derived cell-free DNA and endomyocardial biopsy with respect to rejection	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.	3 years
Secondary	Cost analysis 1	Costs of heart transplantation during the first year post-transplantation	5 years
Secondary	Rejection	Cumulative incidence of rejection (according to the biopsy grading system provided by the International Society of Heart and Lung Transplantation)	5 years
Secondary	Graft-vasculopathy	Cumulative incidence of graft-vasculopathy	5 years
Secondary	Overweight	Prevalence of overweight (BMI >25) and obesity (BMI>30)	5 years
Secondary	Quality of life	Health-related quality of life as measured by EQ5D	5 years
Secondary	Survival	Survival	5 years
Secondary	Re-transplantation	Proportion of patients who have undergone re-transplantation	5 years
Secondary	GFR (glomerular filtration rate)	Renal function evaluated by calculated and measured GFR (Iohexol or Cr-Clearance)	1 year
Secondary	GFR (glomerular filtration rate)	Renal function evaluated by calculated and measured GFR (Iohexol or Cr-Clearance)	3 years
Secondary	GFR (glomerular filtration rate)	Renal function evaluated by calculated and measured GFR (Iohexol or Cr-Clearance)	5 years
Secondary	Infections	Cumulative incidence of infections requiring hospital admission	5 years
Secondary	Circulatory support to transplantation	Proportion of patients undergoing heart transplantation from a ventricular assist device or extra-corporeal membrane oxygenation (ECMO) or from mechanical ventilation.	5 years
Secondary	Immunization status	Impact of pre-transplantation immunization status on primary and secondary outcomes	5 years
Secondary	Malignancy	Cumulative incidence of malignancy (post-transplantation lymphoproliferative disorder PTLD and others)	3 years
Secondary	Malignancy	Cumulative incidence of malignancy (PTLD and others)	5 years
Secondary	Prior cardiac surgery	Impact of prior cardiac surgery on other outcomes	5 years
Secondary	Neonatal cardiac surgery	Impact of neonatal (first 4 weeks of life) cardiac surgery on other outcomes	5 years
Secondary	Donor cardiac arrest	Correlation between circulatory arrest in the donor and cardiac function	5 years
Secondary	Donor cardiopulmonary resuscitation (CPR) impact	Impact of CPR of the donor on the incidence of assumed early rejection	3 years
Secondary	Initial immunosuppression	Correlation between initial immunosuppression and the incidence of rejection	5 years
Secondary	Initial immunosuppression and malignancy	Correlation between type of initial immunosuppression and incidence of malignancy	5 years
Secondary	Immunosuppression and adverse effects	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	5 years
Secondary	Immunosuppression and rejection	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	5 years
Secondary	Ischemia time	Correlation between ischemic graft time and cardiac function as measured by echocardiography	5 years
Secondary	Blood products and adverse events	Correlation between the number of blood products (red blood cells, thrombocytes, plasma) given after transplantation and the incidence of adverse effects	5 years
Secondary	Survival	Survival	3 years

External Links

•   Homepage of the Study