ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03477383
Recruitment Status : Recruiting
First Posted : March 26, 2018
Last Update Posted : March 26, 2018
Sponsor:
Collaborators:
Lund University Hospital
Karolinska University Hospital
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment
Heart Transplant Rejection Diagnostic Test: donor-derived cell-free DNA (dd-cfDNA)

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.


Study Type : Observational
Estimated Enrollment : 80 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: A New Biomarker for the Non-invasive Diagnosis of Rejection After Heart Transplantation
Actual Study Start Date : March 1, 2016
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : January 1, 2025

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Adult patients
Adult patients (18 years or older) undergoing heart transplantation
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

Pediatric patients
Pediatric patients (0-17 years) undergoing heart transplantation
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




Primary Outcome Measures :
  1. Comparison of donor-derived cell-free DNA and endomyocardial biopsy [ 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 Outcome Measures :
  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


Biospecimen Retention:   Samples With DNA
Blood plasma (10ml)


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
All patients on waiting list for heart transplantion at the participating centers
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

1. Follow-up outside Sweden


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03477383


Contacts
Contact: Jens Böhmer, MD +46 31 343 8409 jens.bohmer@vgregion.se
Contact: Göran Dellgren, MD, PhD +46 31 342 8863 goran.dellgren@vgregion.se

Locations
Sweden
Transplantation Center, Sahlgrenska University Hospital Recruiting
Gothenburg, Sweden, 41234
Contact: Kristjan Karason, MD, PhD    +46 31 342 7754    kristjan.karason@vgregion.se   
Pediatric Heart Center, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital Recruiting
Gothenburg, Sweden, 41685
Contact: Håkan Wåhlander, MD, PhD    +46 31 343 6714    hakan.wahlander@vgregion.se   
Contact: Jens Böhmer, MD    +46 31 343 8409    jens.bohmer@vgregion.se   
Pediatric Heart Center, Skåne University Hospital Recruiting
Lund, Sweden, 22241
Contact: Katarina Hanseus, MD, PhD    +46 46 171 000    katarina.hanseus@skane.se   
Contact: Thomas Higgins, MD    +46 46 171 000    thomas.higgins@skane.se   
Pediatric Heart Center, Karolinska University Hospital Recruiting
Stockholm, Sweden, 17176
Contact: Maria Sjöborg-Alpman, MD    08-517 700    maria.sjoborg-alpman@karolinska.se   
Sponsors and Collaborators
Vastra Gotaland Region
Lund University Hospital
Karolinska University Hospital
Investigators
Principal Investigator: Jan Sunnegårdh, MD, PhD Pediatric Heart Center, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital

Additional Information:
Responsible Party: Vastra Gotaland Region
ClinicalTrials.gov Identifier: NCT03477383     History of Changes
Other Study ID Numbers: ver 1.0
014-16 ( Other Identifier: Regional ethical review board in Gothenburg )
First Posted: March 26, 2018    Key Record Dates
Last Update Posted: March 26, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Not decided yet.

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Vastra Gotaland Region:
diagnosis
economics
cell-free DNA
digital droplet PCR
heart failure