Rejection of Renal TransplantNCT01315067
Diagnosis of Acute Rejection in Renal Transplant Patients by Urine Mass Spectrometry
An observational study of Rejection of Renal Transplant, run by Hannover Medical School at 8 sites in Germany.
Trial summary
Reliable and timely detection of acute rejections in renal transplant patients is important to preserve the graft function and to prevent premature graft failure. The current gold standard for the rejection diagnosis is a renal biopsy which is usually performed upon an unexplained decline in the graft function… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rejection of Renal Transplant
- How many people
- 600 participants
- Where
- 8 sitesGermany
- Study dates
- Oct 2011to 15 Jun 2017
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with a kidney or combined kidney/pancreas transplantation from several German transplant centres with an acute unexplained allograft dysfunction within the first year of transplantation who require a clinically indicated allograft biopsy
Who may be able to join
- Adult patients with a kidney or combined kidney/pancreas transplantation
- Unexplained renal allograft dysfunction within the first year of transplantation
- Renal allograft biopsy, which is clinically indicated to verify or exclude an acute rejection
Who cannot join
- Lacking consent of the patient to participate in the study
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Germany8 sites
RTW University of Aachen
Aachen, 52074
Charite Universitätsmedizin Berlin
Berlin, 10117
Kliniken der Stadt Köln gGmbH
Cologne, 51109
University of Erlangen-Nuremberg
Erlangen, 90154
Universitätsklinikum Essen
Essen, 45147
Hannover Medical School
Hanover, 30625
Universitätsklinikum Jena
Jena, 07747
Ludwig-Maximilians-Universitätsklinik München
München, 81377
About this study
Official title: Non-invasive Diagnosis of Acute Rejection in Renal Transplant Patients Using Mass Spectrometry of Urine Samples - a Multicentre Diagnostic Phase III Trial
Reliable and timely detection of acute rejections in renal transplant patients is important to preserve the graft function and to prevent premature graft failure. The current gold standard for the rejection diagnosis is a renal biopsy which is usually performed upon an unexplained decline in the graft function (determined by serum creatinine or clearance). Because of the insensitivity of creatinine determinations and the invasiveness of renal biopsies, non-invasive tests have been suggested to diagnose acute rejection including mass spectrometry (MS) analysis of urine samples.
The ability of MS analysis to detect acute rejection has been demonstrated in small studies on selected patients but evidence is lacking that this test is efficacious in the routine setting of the post-transplant patient care. Based on our previous work that established urine peptide sets for acute rejection by MS, a prospective, multicentre diagnostic phase III study will be executed.
The aim of the study is to prove that this test is as equally effective as the allograft biopsy to detect acute rejection in patients that undergo a biopsy for unexplained renal dysfunction. The perspective of this approach is that the test could be used either in place of the biopsy or as decision guidance whether a biopsy is necessary to confirm the presence of rejection. Another perspective is that the MS test (respectively, a simplified test system derived from this method) could be used in the regular post-transplant surveillance for acute rejection, in place of the relatively insensitive procedure with periodic monitoring of the graft function by creatinine determinations.
- Conditions
- Rejection of Renal Transplant
- Keywords
- kidney transplantation, acute rejection, diagnosis, urine analysis, urinary peptides, mass spectrometry, allograft biopsy, pathology, diagnostic study
- Medical subject headings
- Disease
What is being measured
The primary outcome is the main question the study is designed to answer.
Ability of the urine mass spectrometry test to diagnose acute renal allograft rejection, compared to the gold standard 'allograft biopsy'
In patients with unexplained renal allograft dysfunction who get an allograft biopsy to clarify if an acute rejection is present, a simultaneous urine sample will be taken.
The peptide pattern of this urine sample is analyzed by mass spectrometry and a diagnosis is made (rejection present/not present) based on a pre-defined peptide pattern which was established to detect acute allograft rejection.
In the primary outcome analysis, the sensitivity and specificity of the rejection diagnosis by the urine test is compared to the diagnosis made by the allograft biopsy.
Measured: Results of the urine test will be assessed in relation to the simultaneously performed allograft biopsy (1 day)
Secondary outcomes (3)
Sensitivity and specificity of the urine test to diagnose acute renal allograft rejection in subgroups with different severity grades of the rejection
Sensitivity/specificity measures for the urine test will be determined in subgroups of patients with different severity of the rejection. Severity grading is based on the pathomorphological classification of the rejection (according to the BANFF classification) and on the functional impairment of the allograft at the time of rejection diagnosis.
Measured: Results of the urine test will be assessed in relation to the simultaneously performed allograft biopsy (1 day)
Sensitivity and specificity of the urine test to diagnose acute renal allograft rejection in subgroups with kidney transplantation alone and with combined pancreas/kidney transplantation
Sensitivity/specificity measures for the urine test will be determined in subgroups of patients who have a kidney transplant or a combined pancreas/kidney transplant.
Measured: Results of the urine test will be assessed in relation to the simultaneously performed allograft biopsy (1 day)
Sensitivity and specificity of the urine test to diagnose acute renal allograft rejection in subgroups with concurrent infection
Sensitivity/specificity measures for the urine test will be determined in subgroups of patients who have concurrent infections at the time of the biopsy and urine sampling such as cytomegaly virus, polyoma virus, and urinary tract infection. The analysis intends to identify potential interference of these conditions with the urine mass spectrometry test.
Measured: Results of the urine test will be assessed in relation to the simultaneously performed allograft biopsy (1 day)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2011 (estimated)
- Study startOct 2011
- Primary completionMar 2017
- Study completion15 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Rejection of Renal TransplantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Cross-sectional
- Enrolment
- 600 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hannover Medical School
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wilfried Gwinner, Hannover Medical School
- Investigators
- Wilfried Gwinner, Prof. /MD, Principal investigator, Hannover Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01315067
- Sponsor's protocol ID
- MS-GW4/6-1
- Status last verified
- Aug 2017
- First submitted
- 14 Mar 2011
- Last updated
- 10 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Wittke S, Haubitz M, Walden M, Rohde F, Schwarz A, Mengel M, Mischak H, Haller H, Gwinner W. Detection of acute tubulointerstitial rejection by proteomic analysis of urinary samples in renal transplant recipients. Am J Transplant. 2005 Oct;5(10):2479-88. doi: 10.1111/j.1600-6143.2005.01053.x.
PubMed 16162198Metzger J, Chatzikyrkou C, Broecker V, Schiffer E, Jaensch L, Iphoefer A, Mengel M, Mullen W, Mischak H, Haller H, Gwinner W. Diagnosis of subclinical and clinical acute T-cell-mediated rejection in renal transplant patients by urinary proteome analysis. Proteomics Clin Appl. 2011 Jun;5(5-6):322-33. doi: 10.1002/prca.201000153. Epub 2011 Apr 29.
PubMed 21538920Zapf A, Gwinner W, Karch A, Metzger J, Haller H, Koch A. Non-invasive diagnosis of acute rejection in renal transplant patients using mass spectrometry of urine samples - a multicentre phase 3 diagnostic accuracy study. BMC Nephrol. 2015 Sep 15;16:153. doi: 10.1186/s12882-015-0146-x.
PubMed 26374548
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-invasive Diagnosis of Acute Rejection in Renal Transplant Patients Using Mass Spectrometry of Urine Samples - a Multicentre Diagnostic Phase III Trial
- ClinicalTrials.gov ID
- NCT01315067
- Acronym / sponsor ID
- MS-GW4/6-1
- Conditions
- Rejection of Renal Transplant
- Keywords
- kidney transplantation, acute rejection, diagnosis, urine analysis, urinary peptides, mass spectrometry, allograft biopsy, pathology
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 600 participants (actual)
- Lead sponsor
- Hannover Medical SchoolUniversity, hospital or other
- Study start
- Oct 2011
- Primary completion
- Mar 2017 (actual)
- Study completion
- 15 Jun 2017 (actual)
- First posted
- 15 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Reliable and timely detection of acute rejections in renal transplant patients is important to preserve the graft function and to prevent premature graft failure. The current gold standard for the rejection diagnosis is a renal biopsy which is usually performed upon an unexplained decline in the graft function (determined by serum creatinine or clearance). Because of the insensitivity of creatinine determinations and the invasiveness of renal biopsies, non-invasive tests have been suggested to diagnose acute rejection including mass spectrometry (MS) analysis of urine samples.
The ability of MS analysis to detect acute rejection has been demonstrated in small studies on selected patients but evidence is lacking that this test is efficacious in the routine setting of the post-transplant patient care. Based on our previous work that established urine peptide sets for acute rejection by MS, a prospective, multicentre diagnostic phase III study will be executed.
The aim of the study is to prove that this test is as equally effective as the allograft biopsy to detect acute rejection in patients that undergo a biopsy for unexplained renal dysfunction. The perspective of this approach is that the test could be used either in place of the biopsy or as decision guidance whether a biopsy is necessary to confirm the presence of rejection. Another perspective is that the MS test (respectively, a simplified test system derived from this method) could be used in the regular post-transplant surveillance for acute rejection, in place of the relatively insensitive procedure with periodic monitoring of the graft function by creatinine determinations.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with a kidney or combined kidney/pancreas transplantation from several German transplant centres with an acute unexplained allograft dysfunction within the first year of transplantation who require a clinically indicated allograft biopsy
Key inclusion criteria (3 listed)
- Adult patients with a kidney or combined kidney/pancreas transplantation
- Unexplained renal allograft dysfunction within the first year of transplantation
- Renal allograft biopsy, which is clinically indicated to verify or exclude an acute rejection
Key exclusion criteria (1 listed)
- Lacking consent of the patient to participate in the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Ability of the urine mass spectrometry test to diagnose acute renal allograft rejection, compared to the gold standard 'allograft biopsy'
Time frame: Results of the urine test will be assessed in relation to the simultaneously performed allograft biopsy (1 day)
In patients with unexplained renal allograft dysfunction who get an allograft biopsy to clarify if an acute rejection is present, a simultaneous urine sample will be taken. The peptide pattern of this urine sample is analyzed by mass spectrometry and a diagnosis is made (rejection present/not present) based on a pre-defined peptide pattern which was established to detect acute allograft rejection. In the primary outcome analysis, the sensitivity and specificity of the rejection diagnosis by the urine test is compared to the diagnosis made by the allograft biopsy.
3 secondary outcomes
Sensitivity and specificity of the urine test to diagnose acute renal allograft rejection in subgroups with different severity grades of the rejection
Time frame: Results of the urine test will be assessed in relation to the simultaneously performed allograft biopsy (1 day)
Sensitivity and specificity of the urine test to diagnose acute renal allograft rejection in subgroups with kidney transplantation alone and with combined pancreas/kidney transplantation
Time frame: Results of the urine test will be assessed in relation to the simultaneously performed allograft biopsy (1 day)
Sensitivity and specificity of the urine test to diagnose acute renal allograft rejection in subgroups with concurrent infection
Time frame: Results of the urine test will be assessed in relation to the simultaneously performed allograft biopsy (1 day)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2017.
- Background: PubMed 16162198Wittke S, Haubitz M, Walden M, Rohde F, Schwarz A, Mengel M, Mischak H, Haller H, Gwinner W. Detection of acute tubulointerstitial rejection by proteomic analysis of urinary samples in renal transplant recipients. Am J Transplant. 2005 Oct;5(10):2479-88. doi: 10.1111/j.1600-6143.2005.01053.x.
- Background: PubMed 21538920Metzger J, Chatzikyrkou C, Broecker V, Schiffer E, Jaensch L, Iphoefer A, Mengel M, Mullen W, Mischak H, Haller H, Gwinner W. Diagnosis of subclinical and clinical acute T-cell-mediated rejection in renal transplant patients by urinary proteome analysis. Proteomics Clin Appl. 2011 Jun;5(5-6):322-33. doi: 10.1002/prca.201000153. Epub 2011 Apr 29.
- Derived from this study: PubMed 26374548Zapf A, Gwinner W, Karch A, Metzger J, Haller H, Koch A. Non-invasive diagnosis of acute rejection in renal transplant patients using mass spectrometry of urine samples - a multicentre phase 3 diagnostic accuracy study. BMC Nephrol. 2015 Sep 15;16:153. doi: 10.1186/s12882-015-0146-x.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wilfried Gwinner, Prof. /MD principal investigator
Hannover Medical School
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rejection of Renal Transplant, run by Hannover Medical School at 8 sites in Germany.
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 3 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 10 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Germany. 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?
Ability of the urine mass spectrometry test to diagnose acute renal allograft rejection, compared to the gold standard 'allograft biopsy' (time frame: Results of the urine test will be assessed in relation to the simultaneously performed allograft biopsy (1 day)). 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 NCT01315067, which also lists 3 linked publications.
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 10 Aug 2017.