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Heart Transplant RejectionBIODRAFTNCT03477383

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

An observational study of Heart Transplant Rejection, run by Vastra Gotaland Region at 4 sites in Sweden.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Any age
Conditions the study is for
Heart Transplant Rejection
What is being tested?
donor-derived cell-free DNA (dd-cfDNA)
How many people
134 participants
Where
4 sitesSweden
Study dates
1 Mar 2016to 31 Dec 2021
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Study population: All patients on waiting list for heart transplantion at the participating centers

Who may be able to join

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

Who cannot join

  • 1. Follow-up outside Sweden

Trial locations and contacts

4 sites in 1 country.

Sweden4 sites

  • Transplantation Center, Sahlgrenska University Hospital

    Gothenburg, 41234

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

    Gothenburg, 41685

  • Pediatric Heart Center, Skåne University Hospital

    Lund, 22241

  • Pediatric Heart Center, Karolinska University Hospital

    Stockholm, 17176

Other trials in Sweden

About this study

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.

Read the 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.

Being tested
donor-derived cell-free DNA (dd-cfDNA)
Keywords
diagnosis, economics, cell-free DNA, digital droplet PCR, heart failure
Medical subject headings
Disease, Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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

Study groups in NCT03477383
Study groupRoleWhat they receive
Adult patientsAdult patients (18 years or older) undergoing heart transplantation
Receives: Diagnostic Test: donor-derived cell-free DNA (dd-cfDNA)
Pediatric patientsPediatric patients (0-17 years) undergoing heart transplantation
Receives: Diagnostic Test: donor-derived cell-free DNA (dd-cfDNA)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 3 years

Secondary outcomes (26)

  1. Cost analysis 1

    Costs of heart transplantation during the first year post-transplantation

    Measured: 5 years

  2. Rejection

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

    Measured: 5 years

  3. Graft-vasculopathy

    Cumulative incidence of graft-vasculopathy

    Measured: 5 years

  4. Overweight

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

    Measured: 5 years

  5. Quality of life

    Health-related quality of life as measured by EQ5D

    Measured: 5 years

  6. Survival

    Survival

    Measured: 5 years

  7. Re-transplantation

    Proportion of patients who have undergone re-transplantation

    Measured: 5 years

  8. GFR (glomerular filtration rate)

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

    Measured: 1 year

  9. GFR (glomerular filtration rate)

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

    Measured: 3 years

  10. GFR (glomerular filtration rate)

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

    Measured: 5 years

  11. Infections

    Cumulative incidence of infections requiring hospital admission

    Measured: 5 years

  12. 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.

    Measured: 5 years

  13. Immunization status

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

    Measured: 5 years

  14. Malignancy

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

    Measured: 3 years

  15. Malignancy

    Cumulative incidence of malignancy (PTLD and others)

    Measured: 5 years

  16. Prior cardiac surgery

    Impact of prior cardiac surgery on other outcomes

    Measured: 5 years

  17. Neonatal cardiac surgery

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

    Measured: 5 years

  18. Donor cardiac arrest

    Correlation between circulatory arrest in the donor and cardiac function

    Measured: 5 years

  19. Donor cardiopulmonary resuscitation (CPR) impact

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

    Measured: 3 years

  20. Initial immunosuppression

    Correlation between initial immunosuppression and the incidence of rejection

    Measured: 5 years

  21. Initial immunosuppression and malignancy

    Correlation between type of initial immunosuppression and incidence of malignancy

    Measured: 5 years

  22. 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

    Measured: 5 years

  23. 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

    Measured: 5 years

  24. Ischemia time

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

    Measured: 5 years

  25. 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

    Measured: 5 years

  26. Survival

    Survival

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Mar 2018
  2. Study start1 Mar 2016
  3. Primary completion31 Dec 2021
  4. Study completion31 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
134 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03477383
Sponsor's protocol ID
ver 1.0
Other IDs
014-16
Acronym
BIODRAFT
Status last verified
Oct 2021
First submitted
15 Mar 2018
Last updated
2 May 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: Not decided yet.

Publications

  • Bohmer J, Wasslavik C, Andersson D, Stahlberg A, Jonsson M, Wahlander H, Karason K, Sunnegardh J, Nilsson S, Asp J, Dellgren G, Ricksten A. Absolute Quantification of Donor-Derived Cell-Free DNA in Pediatric and Adult Patients After Heart Transplantation: A Prospective Study. Transpl Int. 2023 Oct 30;36:11260. doi: 10.3389/ti.2023.11260. eCollection 2023.

    PubMed 37965628

Questions about this trial

What is this clinical trial studying?

An observational study of Heart Transplant Rejection, run by Vastra Gotaland Region at 4 sites in Sweden.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Comparison of donor-derived cell-free DNA and endomyocardial biopsy with respect to rejection (time frame: 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03477383, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2022.

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