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Kidney Transplant Failure and RejectionBIOTRAIMNCT05816486

BIOtechnology Applied to Renal TRansplantation With IMmunobiogram

An observational study of Kidney Transplant Failure and Rejection, run by Biohope Scientific Solutions for Human Health, S.L. at 15 sites in 5 countries.

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

Immunobiogram (IMBG) is a novel in vitro diagnostic bioassay developed by Biohope Scientific Solutions for Human Health SL, that allows to measure the pharmacodynamic response to individual immunosuppressive drugs in patients with a renal transplantation. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Kidney Transplant Failure and Rejection
What is being tested?
Immunobiogram
How many people
443 participants
Where
15 sitesin 5 countries
Study dates
1 Mar 2022to 30 Jun 2024
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: 1. Prospective longitudinal cohort: all patients who are to receive a kidney transplant and meet the screening criteria for this study cohort. This cohort will be recruited in sites that routinely perform a Protocol Biopsy (PB) one year after transplant. 2. Cross-sectional cohort: patients in whom an Indication Biopsy (IB) is to be performed due to suspicion of rejection. This cohort may be recruited in all sites participating in the study and patients will be enrolled competitively. 3. Control cohort: cross-sectional cohort to include patients who have received a kidney transplant or a re-transplant less than 5 years before inclusion in the study and have shown a stable clinical course after 6 months post-transplant. An IMBG will be performed coinciding with the study visit.

Who may be able to join

  • Longitudinal cohort:
  • Patients > 18 years of age.
  • Candidate to receive a kidney transplant or re-transplant.
  • Patients in whom it is planned to routinely perform a protocol biopsy one year after the kidney transplant for which there is no contraindication at the time of inclusion in the study.
  • Patients in whom a pre-transplant blood sample can be drawn that is viable for the processing of an IMBG.
  • Patients who give their written informed consent to participate in the study.
Show all 32Show fewer
  • Cross-sectional cohort:
  • Patients > 18 years of age.
  • Patients who have received a kidney transplant or re-transplant less than 3 years before inclusion in the study.
  • Patients in whom an indication biopsy is to be performed due to suspicion of rejection.
  • Patients in whom a blood sample can be drawn in a period of time less than 8 days before or after the Indication Biopsy that is viable for the processing of an IMBG.
  • Patients who give their written informed consent to participate in the study.
  • Exclusion Criteria (PROSPECTIVE AND CROSS-SECTIONAL COHORT):
  • Patient with a double transplant (kidney + other organ).
  • Contraindication for performing a renal graft biopsy.
  • Active autoimmune diseases in the 12 months prior to the study visit (with systemic inflammatory exacerbation in the year prior to study inclusion, despite immunosuppressive therapy).
  • Very elderly cadaver donor transplant (>80 years of age).
  • Donors in asystole II.
  • Recurrent primary kidney disease in the case of primary focal and segmental hyalinosis or hemolytic-uremic syndrome.
  • Active HIV, HBV or HCV infection or other severe infections (to prevent risks in the processing of samples in conventional laboratories).
  • Concomitant medical conditions that may affect the patient's participation in the study.
  • Control cohort:
  • Patients > 18 years of age.
  • Patients who have received a kidney transplant or re-transplant less than 5 years before inclusion in the study.
  • A stable course after 6 months post-transplant defined as:
  • Lack of renal impairment (GFR > 50 ml/min/1.73 m2 and proteinuria < 300 mg/g)
  • No previous rejection episodes and no graft indication biopsies
  • No positive dnDSA
  • No change in the active principle of immunosuppressive drugs in the last 6 weeks
  • No opportunistic infections in the last 6 months
  • Patients in whom a blood sample can be drawn suitable for IMBG processing.
  • Patients (or their legal representative) who give their written informed consent to participate in the study.

Who cannot join

  • Patient with a double transplant (kidney + other organ).
  • Active autoimmune diseases in the 12 months prior to the study visit (with systemic inflammatory exacerbation in the year prior to study inclusion, despite immunosuppressive therapy).
  • Very elderly cadaver donor transplant (>80 years of age).
  • Donors in asystole II.
  • Recurrent primary kidney disease in the case of primary focal and segmental hyalinosis or hemolytic-uremic syndrome.
  • Active HIV, HBV or HCV infection or other severe infections (to prevent risks in the processing of samples in conventional laboratories).
  • Concomitant medical conditions that may affect the patient's participation in the study.

Trial locations and contacts

15 sites in 5 countries.

15 sites in 5 countries

Spain10 sites
  • Fundació Puigvert

    Barcelona

  • Hospital Clínic de Barcelona

    Barcelona

  • Hospital del Mar

    Barcelona

  • Hospital Universitario Puerta del Mar

    Cadiz

  • Hospital Clínico San Carlos

    Madrid

  • Hospital Universitario 12 Octubre

    Madrid

  • Hospital Universitario La Paz

    Madrid

  • Hospital Universitario Puerta de Hierro

    Madrid

  • Hospital Universitario Marqués de Valdecilla

    Santander

  • Hospital Universitario Dr. Peset

    Valencia

Other trials in Spain

Germany2 sites
  • Charité Universitätsmedizin Berlin

    Berlin

  • Universitätsklinikum Heidelberg

    Heidelberg

Other trials in Germany

Brazil1 site
  • Hospital Do Rim

    Brasil

Other trials in Brazil

France1 site
  • University Hospital Grenoble

    Grenoble

Other trials in France

Sweden1 site
  • Uppsala University Hospital

    Uppsala

Other trials in Sweden

About this study

Official title: Longitudinal Observational Study to Determine the Correlation Between Patient's Pharmacodynamic Response to Immunosuppressants Measured in Vitro With IMMUNOBIOGRAM and of Rejection in Graft Biopsies in Patients With Renal Transplantation

Immunobiogram (IMBG) is a novel in vitro diagnostic bioassay developed by Biohope Scientific Solutions for Human Health SL, that allows to measure the pharmacodynamic response to individual immunosuppressive drugs in patients with a renal transplantation. Pharmacodynamics can complement the already available pharmacokinetic information on immunosuppressants and enable a more individualized evaluation of the immunosuppressive therapy.

The aim of this study is to evaluate the association between the pharmacodynamic response to individual immunosuppressants taken by the patient measured in vitro with IMBG and the existence of signs of graft rejection in biopsies (upon indication or protocol) performed in a sample of kidney transplant patients.

The main hypothesis is that a lower sensitivity to the immunosuppressive drugs taken by the patient will be associated with a higher probability of rejection.

Read the detailed description

Immunobiogram (IMBG) is a novel bioassay that allows to measure in vitro the inhibitory effect of a battery of individual immunosuppressants on the patient's immune cells (immunologically stimulated PBMCs).

Studies conducted in kidney transplant patients have shown that IMBG is a valid and accurate instrument, capable of determining each patient's pharmacodynamic response profile to individual immunosuppressive drugs.

Health professionals who monitor kidney transplant patients currently have information only on immunosuppressant pharmacokinetics to adjust the regimen of the immunosuppressants they use to treat the patients to avoid graft rejection. The pharmacodynamic measurement of the in vitro effect of each immunosuppressant in the patient could complement the pharmacokinetic information and enable more personalized approaches.

The main objective of this study is to evaluate the association between the pharmacodynamic response to individual immunosuppressants taken by the patient measured with IMBG and the existence of signs of graft rejection in biopsies (upon indication or protocol) performed in a sample of kidney transplant patients.

A longitudinal follow-up cohort of patients will be recruited from prior to the transplant (at sites that regularly perform a protocol graft biopsy after a year) and a cross-sectional cohort of patients will also be included when an indication biopsy is performed during the first five years after kidney transplantation due to a suspicion of rejection at sites that do not routinely perform protocol biopsies.

Given that one of the main challenges that clinicians face in the follow-up of patients is to reduce the risk of renal graft rejection, while minimizing the incidence of secondary effects related to immunosuppressive therapy, it is proposed as a secondary objective to evaluate in the longitudinal cohort the incidence of "therapeutical failure" due to graft failure or due to the appearance of serious adverse effects attributable to immunosuppression and analyze its relationship with the profile of sensitivity to immunosuppressants taken by the patient measured with IMBG.

It will be also evaluated if the IMBG sensitivity to immunosuppressive drugs measured pretransplant predict the ocurrence of rejection or adverse events during the first year postransplant.

Finally, the changes over time presented by the IMBG in various determinations and the correlation between IMBG results and other lymphocyte activation parameters obtained by flow cytometry will be analyzed.

Being tested
Immunobiogram
Keywords
Kidney Transplant Rejection, Immunosuppression, Immune cell bioassay, Pharmacodynamics, Oportunistic infections
Medical subject headings
Rejection, Psychology

What participants receive

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

  • ImmunobiogramDiagnostic test

    This is not an interventional study. However the assay being tested on the blood samples of all enrolled participants is the Immunobiogram (IMBG). IMBG is an in vitro diagnostic immunoassay which can obtain dose-response curves that describe the inhibitory effect of each immunosuppressant on immune response cells (immunologically stimulated PBMCs) in kidney transplant patients.

Study groups in NCT05816486
Study groupRoleWhat they receive
Prospective - LongitudinalLongitudinal follow-up cohort in which all patients who are going to receive a kidney transplant and meet the selection criteria for this study cohort will be included. This cohort will be recruited at sites that routinely perform Protocol Biopsies (PB) one year after transplant. A pre-transplant and post-transplant follow-up IMBG at 3, 6, 9 and 12 months will be performed, and additional IMBG will be carried out when an indication biopsy is required due to a suspected rejection during the patients' follow-up. A protocol biopsy will be performed after one year of follow-up of the patients.
Receives: Diagnostic Test: Immunobiogram
Cross-sectionalPatients in whom an Indication Biopsy (IB) is to be performed due to suspicion of rejection. This cohort may be recruited in all sites participating in the study, including sites where annual protocol biopsies are not routinely performed. An IMBG will be performed coinciding with the IB. This cohort will include patients who have had their transplant for less than 5 years.
Receives: Diagnostic Test: Immunobiogram
ControlPatients who have received a kidney transplant or a re-transplant less than 5 years before inclusion in the study and have shown a stable clinical course after 6 months from the RT, defined as: patients without previous rejection episodes nor indication biopsies, who do not show signs of renal impairment and are dnDSA negative, without changes in immunosuppressive drugs in the last 6 weeks and without opportunistic infections in the last six months before entering in the study. An IMBG will be performed coinciding with the only visit.
Receives: Diagnostic Test: Immunobiogram

What is being measured

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

  1. Proportion of patients with BPAR in biopsies (following BANFF 2019 criteria) who present Low Sensitivity to the prescribed Immunosupressive drugs in IMBG

    Proportion of patients with BPAR (BANFF 2019 2, 3 or 4) who present Low Sensitivity to the prescribed Immunosupressive drugs in IMBG in longitudinal cohort in 1 year- Protocol Biopsies or in Indication Biopsies and in the cross sectional cohort in Indication Biopsies

    Measured: 12 months in the prospective follow-up cohort.

Secondary outcomes (9)
  1. Proportion of patients with impairment in renal function AND BPAR or inflammatory damage in biopsies or the presence of dnDSA in the last determination who present low sensitivity to the individual immunosuppressive drugs in IMBG

    Proportion of patients with impairment in renal function AND signs of rejection (BPAR) or inflammatory damage in protocol/indication biopsies or the presence of de novo antidonor specific antibodies (dnDSA) in the last determination prior to the biopsy who present low sensitivity to individual prescribed immunosuppressive drugs in IMBG

    Measured: 12 months

  2. Proportion of patients with impairment in renal function AND BPAR or inflammatory damage in biopsies or the presence of dnDSA in the last determination who present low sensitivity to all prescribed immunosuppressive drugs in IMBG

    Proportion of patients with impairment in renal function AND signs of rejection (BPAR) or inflammatory damage in protocol/indication biopsies or the presence of de novo antidonor specific antibodies (dnDSA) in the last determination prior to the biopsy who present low sensitivity to all prescribed immunosuppressive drugs in IMBG

    Measured: 12 months

  3. Proportion of patients with therapeutical failure due to rejection who present low sensitivity to the prescribed immunosuppressive drugs in IMBG

    Proportion of patients with therapeutical failure due to rejection who present low sensitivity to the prescribed immunosuppressive drugs in IMBG (Therapeutical failure is defined as the incidence of graft loss and/or BPAR and/or dnDSA)

    Measured: 12 months in the prospective follow-up cohort.

  4. Proportion of patients with with therapeutical failure due adverse effects attributable to immunosuppression who present high sensitivity /or low sensitivity and high doses to the prescribed immunosuppressive drugs in IMBG

    Proportion of patients with therapeutical failure due adverse effects attributable to immunosuppression who present high sensitivity /or low sensitivity and high doses to the prescribed immunosuppressive drugs in IMBG Therapeutical failure is defined as the incidence of opportunistic infection by Cytomegalovirus (CMV) (symptomatic or not) and/or BK polyomavirus (BKV) and/or 3 or more hospitalizations due to infections during the patient's follow-up).

    Measured: 12 months in the prospective follow-up cohort.

  5. Proportion of patients whose pre-transplant IMBG predicts the incidence of events during the patients' follow up

    Proportion of patients whose pre-transplant IMBG predicts the incidence of events (graft rejection failure or failure due to adverse effects attributable to immunosuppression) during the patients' follow up

    Measured: 12 months

  6. Correlation between IMBG values and other lymphocyte activation markers

    Correlation between IMBG values and other lymphocyte activation markers (CD69, CD25) for each immunosuppressive drug tested with IMBG over time

    Measured: In the prospective cohort at 3, 6, 9, and 12 months

  7. Distribution of pre-transplant IMBG values and post-transplant at 3, 6, 9, and 12 months

    Distribution of pre-transplant IMBG values and post-transplant at 3, 6, 9, and 12 months

    Measured: In the prospective cohort at 3, 6 , 9 and 12 months

  8. Adherence to treatment measured with Morisky Green Scale (MMAS).

    Adherence to treatment measured with Morisky Green Scale (MMAS, score 0 (worst adherence) - 4 (best adherence), at 6 months and at one year.

    Measured: at 6 and at 12 months

  9. Quality of Life perceived by the patient, measured with EQ-5D-5L questionnaire.

    Quality of Life perceived by the patient, measured with European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) questionnaire (score 0 (worst health) - 100 (best health) at baseline and at one year.

    Measured: baseline and at 12 months

Timeline

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

  1. First posted18 Apr 2023
  2. Study start1 Mar 2022
  3. Primary completion30 Jun 2024
  4. Study completion30 Jun 2024

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
443 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05816486
Sponsor's protocol ID
BH-IMBG-TR-2021
Acronym
BIOTRAIM
Status last verified
Jul 2024
First submitted
9 Feb 2023
Last updated
18 Jul 2024
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Portoles JM, Jimenez C, Janeiro D, Lopez-Oliva MO, Ortega-Carrion A, Blanquez D, Arribas L, Gomez C, Diez T, Pascual J, Portero I. The Immunobiogram, a Novel In Vitro Assay to Evaluate Treatment Resistance in Patients Receiving Immunosuppressive Therapy. Front Immunol. 2021 Jan 25;11:618202. doi: 10.3389/fimmu.2020.618202. eCollection 2020.

    PubMed 33569062
  • Pascual J, Jimenez C, Krajewska M, Seron D, Kotton CN, Portoles J, Witzke O, Sorensen SS, Andres A, Crespo M, Paz-Artal E, Diez T, Ortega A, Portero I. The Immunobiogram, a novel in vitro diagnostic test to measure the pharmacodynamic response to immunosuppressive therapy in kidney transplant patients. Transpl Immunol. 2022 Dec;75:101711. doi: 10.1016/j.trim.2022.101711. Epub 2022 Sep 9.

    PubMed 36096417
  • Pascual J, Crespo M, Portoles J, Jimenez C, Ortega-Carrion A, Diez T, Portero I. The IMBG Test for Evaluating the Pharmacodynamic Response to Immunosuppressive Therapy in Kidney Transplant Patients: Current Evidence and Future Applications. Int J Mol Sci. 2023 Mar 8;24(6):5201. doi: 10.3390/ijms24065201.

    PubMed 36982276

Questions about this trial

What is this clinical trial studying?

An observational study of Kidney Transplant Failure and Rejection, run by Biohope Scientific Solutions for Human Health, S.L. at 15 sites in 5 countries.

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 32 inclusion and 7 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 18 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Spain, Germany, Brazil, France, 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?

Proportion of patients with BPAR in biopsies (following BANFF 2019 criteria) who present Low Sensitivity to the prescribed Immunosupressive drugs in IMBG (time frame: 12 months in the prospective follow-up cohort.). 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 NCT05816486, 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 18 Jul 2024.

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