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NCT Number: NCT03477383

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

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.

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Key information

Conditions

Heart Transplant Rejection Cardiovascular Diseases Disease Heart Diseases Heart Failure Pathologic Processes Pathological Conditions, Signs and Symptoms

Sex eligibility

All sexes

Study type

Observational

Primary location

Pediatric Heart Center, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patient on waiting list for heart transplantation
  • Signed informed consent

Exclusion criteria

  • Follow-up outside Sweden

Treatment and study plan

donor-derived cell-free DNA (dd-cfDNA)

Diagnostic Test

Measurement of dd-cfDNA and comparison against grade of rejection as measured by endomyocardial biopsy, taken simultaneously

Primary outcomes

  1. Comparison of donor-derived cell-free DNA and endomyocardial biopsy with respect to rejection

    Time frame: 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 outcomes

  1. Cost analysis 1

    Time frame: 5 years

    Costs of heart transplantation during the first year post-transplantation

  2. Rejection

    Time frame: 5 years

    Cumulative incidence of rejection (according to the biopsy grading system provided by the International Society of Heart and Lung Transplantation)

  3. Graft-vasculopathy

    Time frame: 5 years

    Cumulative incidence of graft-vasculopathy

  4. Overweight

    Time frame: 5 years

    Prevalence of overweight (BMI >25) and obesity (BMI>30)

  5. Quality of life

    Time frame: 5 years

    Health-related quality of life as measured by EQ5D

  6. Survival

    Time frame: 5 years

    Survival

  7. Re-transplantation

    Time frame: 5 years

    Proportion of patients who have undergone re-transplantation

  8. GFR (glomerular filtration rate)

    Time frame: 1 year

    Renal function evaluated by calculated and measured GFR (Iohexol or Cr-Clearance)

  9. GFR (glomerular filtration rate)

    Time frame: 3 years

    Renal function evaluated by calculated and measured GFR (Iohexol or Cr-Clearance)

  10. GFR (glomerular filtration rate)

    Time frame: 5 years

    Renal function evaluated by calculated and measured GFR (Iohexol or Cr-Clearance)

  11. Infections

    Time frame: 5 years

    Cumulative incidence of infections requiring hospital admission

  12. Circulatory support to transplantation

    Time frame: 5 years

    Proportion of patients undergoing heart transplantation from a ventricular assist device or extra-corporeal membrane oxygenation (ECMO) or from mechanical ventilation.

  13. Immunization status

    Time frame: 5 years

    Impact of pre-transplantation immunization status on primary and secondary outcomes

  14. Malignancy

    Time frame: 3 years

    Cumulative incidence of malignancy (post-transplantation lymphoproliferative disorder PTLD and others)

  15. Malignancy

    Time frame: 5 years

    Cumulative incidence of malignancy (PTLD and others)

  16. Prior cardiac surgery

    Time frame: 5 years

    Impact of prior cardiac surgery on other outcomes

  17. Neonatal cardiac surgery

    Time frame: 5 years

    Impact of neonatal (first 4 weeks of life) cardiac surgery on other outcomes

  18. Donor cardiac arrest

    Time frame: 5 years

    Correlation between circulatory arrest in the donor and cardiac function

  19. Donor cardiopulmonary resuscitation (CPR) impact

    Time frame: 3 years

    Impact of CPR of the donor on the incidence of assumed early rejection

  20. Initial immunosuppression

    Time frame: 5 years

    Correlation between initial immunosuppression and the incidence of rejection

  21. Initial immunosuppression and malignancy

    Time frame: 5 years

    Correlation between type of initial immunosuppression and incidence of malignancy

  22. Immunosuppression and adverse effects

    Time frame: 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

  23. Immunosuppression and rejection

    Time frame: 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

  24. Ischemia time

    Time frame: 5 years

    Correlation between ischemic graft time and cardiac function as measured by echocardiography

  25. Blood products and adverse events

    Time frame: 5 years

    Correlation between the number of blood products (red blood cells, thrombocytes, plasma) given after transplantation and the incidence of adverse effects

  26. Survival

    Time frame: 3 years

    Survival

Sponsors and collaborators

Lead sponsor

Vastra Gotaland Region

Other Gov

Collaborators

  • Karolinska University Hospital
  • Lund University Hospital

Registry information

Acronym: BIODRAFT

Important dates

Study start
2016
Primary completion
2021
Study completion
2021
First posted
Mar 26, 2018
Registry last updated
May 2, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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