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

April 29, 2022 updated by: Vastra Gotaland Region
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
134

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Gothenburg, Sweden, 41234
        • Transplantation Center, Sahlgrenska University Hospital
      • Gothenburg, Sweden, 41685
        • Pediatric Heart Center, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital
      • Lund, Sweden, 22241
        • Pediatric Heart Center, Skåne University Hospital
      • Stockholm, Sweden, 17176
        • Pediatric Heart Center, Karolinska University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

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

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. Follow-up outside Sweden

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
3 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Cost analysis 1
Time Frame: 5 years
Costs of heart transplantation during the first year post-transplantation
5 years
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)
5 years
Graft-vasculopathy
Time Frame: 5 years
Cumulative incidence of graft-vasculopathy
5 years
Overweight
Time Frame: 5 years
Prevalence of overweight (BMI >25) and obesity (BMI>30)
5 years
Quality of life
Time Frame: 5 years
Health-related quality of life as measured by EQ5D
5 years
Survival
Time Frame: 5 years
Survival
5 years
Re-transplantation
Time Frame: 5 years
Proportion of patients who have undergone re-transplantation
5 years
GFR (glomerular filtration rate)
Time Frame: 1 year
Renal function evaluated by calculated and measured GFR (Iohexol or Cr-Clearance)
1 year
GFR (glomerular filtration rate)
Time Frame: 3 years
Renal function evaluated by calculated and measured GFR (Iohexol or Cr-Clearance)
3 years
GFR (glomerular filtration rate)
Time Frame: 5 years
Renal function evaluated by calculated and measured GFR (Iohexol or Cr-Clearance)
5 years
Infections
Time Frame: 5 years
Cumulative incidence of infections requiring hospital admission
5 years
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.
5 years
Immunization status
Time Frame: 5 years
Impact of pre-transplantation immunization status on primary and secondary outcomes
5 years
Malignancy
Time Frame: 3 years
Cumulative incidence of malignancy (post-transplantation lymphoproliferative disorder PTLD and others)
3 years
Malignancy
Time Frame: 5 years
Cumulative incidence of malignancy (PTLD and others)
5 years
Prior cardiac surgery
Time Frame: 5 years
Impact of prior cardiac surgery on other outcomes
5 years
Neonatal cardiac surgery
Time Frame: 5 years
Impact of neonatal (first 4 weeks of life) cardiac surgery on other outcomes
5 years
Donor cardiac arrest
Time Frame: 5 years
Correlation between circulatory arrest in the donor and cardiac function
5 years
Donor cardiopulmonary resuscitation (CPR) impact
Time Frame: 3 years
Impact of CPR of the donor on the incidence of assumed early rejection
3 years
Initial immunosuppression
Time Frame: 5 years
Correlation between initial immunosuppression and the incidence of rejection
5 years
Initial immunosuppression and malignancy
Time Frame: 5 years
Correlation between type of initial immunosuppression and incidence of malignancy
5 years
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
5 years
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
5 years
Ischemia time
Time Frame: 5 years
Correlation between ischemic graft time and cardiac function as measured by echocardiography
5 years
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
5 years
Survival
Time Frame: 3 years
Survival
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Vastra Gotaland Region

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Karolinska University Hospital
Lund University Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jan Sunnegårdh, MD, PhD, Pediatric Heart Center, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 15, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 23, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 26, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 2, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 29, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ver 1.0
  • 014-16 (Other Identifier: Regional ethical review board in Gothenburg)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD Plan Description

Not decided yet.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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