Kidney Transplant Failure and Rejection Clinical Trial
— BIOTRAIMOfficial 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.
Status | Recruiting |
Enrollment | 450 |
Est. completion date | June 30, 2024 |
Est. primary completion date | March 31, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: Longitudinal cohort: 1. Patients > 18 years of age. 2. Candidate to receive a kidney transplant or re-transplant. 3. 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. 4. Patients in whom a pre-transplant blood sample can be drawn that is viable for the processing of an IMBG. 5. Patients who give their written informed consent to participate in the study. Cross-sectional cohort: 1. Patients > 18 years of age. 2. Patients who have received a kidney transplant or re-transplant less than 3 years before inclusion in the study. 3. Patients in whom an indication biopsy is to be performed due to suspicion of rejection. 4. 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. 5. Patients who give their written informed consent to participate in the study. Exclusion Criteria (for both cohorts): 1. Patient with a double transplant (kidney + other organ). 2. Contraindication for performing a renal graft biopsy. 3. 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). 4. Very elderly cadaver donor transplant (>80 years of age). 5. Donors in asystole II. 6. Recurrent primary kidney disease in the case of primary focal and segmental hyalinosis or hemolytic-uremic syndrome. 7. Active HIV, HBV or HCV infection or other severe infections (to prevent risks in the processing of samples in conventional laboratories). 8. Concomitant medical conditions that may affect the patient's participation in the study. |
Country | Name | City | State |
---|---|---|---|
Brazil | Hospital Do Rim | Brasil | |
France | University Hospital Grenoble | Grenoble | |
Germany | Charité Universitätsmedizin Berlin | Berlin | |
Germany | Universitätsklinikum Heidelberg | Heidelberg | |
Spain | Fundació Puigvert | Barcelona | |
Spain | Hospital Clínic de Barcelona | Barcelona | |
Spain | Hospital del Mar | Barcelona | |
Spain | Hospital Clínico San Carlos | Madrid | |
Spain | Hospital Universitario 12 Octubre | Madrid | |
Spain | Hospital Universitario La Paz | Madrid | |
Spain | Hospital Universitario Puerta de Hierro | Madrid | |
Spain | Hospital Universitario Puerta del Mar | Málaga | |
Spain | Hospital Universitario Marqués de Valdecilla | Santander | |
Spain | Hospital Universitario Dr. Peset | Valencia | |
Sweden | Uppsala University Hospital | Uppsala |
Lead Sponsor | Collaborator |
---|---|
Biohope Scientific Solutions for Human Health, S.L. |
Brazil, France, Germany, Spain, Sweden,
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. — View Citation
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. — View Citation
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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 who present Low Sensitivity to the prescribed Immunosupressive drugs in IMBG Longitudinal cross-sectional cohorts 1 year- Protocol Biopsies and Indication Biopsies, BPAR following BANFF 2019 criteria. | 12 months in the prospective follow-up cohort. | |
Secondary | 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) | 12 months in the prospective follow-up cohort. | |
Secondary | 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 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). | 12 months in the prospective follow-up cohort. | |
Secondary | Correlation between IMBG values and other lymphocyte activation markers | Correlation between IMBG values and other lymphocyte activation markers (CD69, CD25, IL-2, IFN-gamma) for each immunosuppressive drug tested with IMBG over time | In the prospective cohort at 3, 6, 9, and 12 months | |
Secondary | 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 | In the prospective cohort at 3, 6 , 9 and 12 months | |
Secondary | 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. | at 6 and at 12 months | |
Secondary | 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. | baseline and at 12 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT04057742 -
AlloSure for the Monitoring of Antibody Mediated Processes After Kidney Transplantation
|
||
Recruiting |
NCT03465397 -
Individualization of the Immunological Risk Based on Selective Biomarkers in Living-donor Renal Recipients
|
Phase 4 | |
Completed |
NCT03437577 -
Comparison of the Cognitive and Motor Effects of Treatment Between an Immediate- and Extended-release Tacrolimus (Envarsus® XR) Based Immunosuppression Regimen in Kidney Transplant Recipients
|
Phase 1/Phase 2 | |
Not yet recruiting |
NCT05282966 -
Assessment of QSantâ„¢ for Underlying Allograft Rejection
|
||
Recruiting |
NCT04388930 -
The Microbiota in Kidney Donation and Transplantation
|
||
Completed |
NCT03611621 -
A Follow up Study of Patients Treated With Imlifidase Prior to Kidney Transplantation
|
||
Recruiting |
NCT05397821 -
Pediatric Kidney Transplantation, Ureteroneocystostomy Techniques
|
||
Completed |
NCT04019353 -
Cf-DNA Assay During Treatment of Acute Rejection
|
||
Active, not recruiting |
NCT05806749 -
Immunological Tolerance in Patients With Mismatched Kidney Transplants
|
Phase 1 | |
Recruiting |
NCT04936282 -
Treatment of Early Borderline Lesions in Low Immunological Risk Kidney Transplant Patients (TRAINING)
|
Phase 4 | |
Enrolling by invitation |
NCT05285878 -
Fingolimod for the Abrogation of Interstitial Fibrosis and Tubular Atrophy Following Kidney Transplantation
|
Phase 2 | |
Recruiting |
NCT04526431 -
Tacrolimus Pharmacokinetic Subpopulations
|
||
Active, not recruiting |
NCT03511560 -
Envarsus on the Effect of Total Tacrolimus Dose/Trough Level Ratio on Renal Function (eGFR) in Kidney Transplantation
|
Phase 4 | |
Recruiting |
NCT03438773 -
Prospective Pilot Feasibility Study Comparing Envarsus Once-a-day to Tacrolimus Twice-a-day Immunosuppressive Regimen on Drug Bioavailability in Hispanic First Time Kidney Transplant Recipients
|
Phase 1 | |
Completed |
NCT05388955 -
Risk Assessment Tool for Graft Survival in Pediatric Kidney Transplantation
|
||
Completed |
NCT06394596 -
Predicting Prognostic Factors in Kidney Transplantation Using A Machine Learning
|
||
Completed |
NCT04413916 -
MiRNA in Kidney Transplantation: Association With Kidney Graft Function and Disease Process
|
||
Completed |
NCT03466775 -
Anti-Angiotensin II Type 1 Receptor Antibodies and Kidney Transplant Outcomes
|
N/A | |
Active, not recruiting |
NCT04733131 -
Long-term Outcomes After Conversion to Belatacept
|
||
Active, not recruiting |
NCT03380962 -
Clazakizumab in Highly-HLA Sensitized Patients Awaiting Renal Transplant
|
Phase 1/Phase 2 |