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
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 443
- 试验地点
- 15
- 主要终点
- Proportion of patients with BPAR in biopsies (following BANFF 2019 criteria) who present Low Sensitivity to the prescribed Immunosupressive drugs in IMBG
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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:
- •Inclusion criteria:
- •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.
- •Exclusion criteria:
- •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.
排除标准
- 未提供
结局指标
主要结局
Proportion of patients with BPAR in biopsies (following BANFF 2019 criteria) who present Low Sensitivity to the prescribed Immunosupressive drugs in IMBG
时间窗: 12 months in the prospective follow-up cohort.
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
次要结局
- Proportion of patients whose pre-transplant IMBG predicts the incidence of events during the patients' follow up(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)
- Proportion of patients with therapeutical failure due to rejection who present low sensitivity to the prescribed immunosuppressive drugs in IMBG(12 months in the prospective follow-up cohort.)
- Correlation between IMBG values and other lymphocyte activation markers(In the prospective cohort at 3, 6, 9, and 12 months)
- 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(12 months in the prospective follow-up cohort.)
- 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(12 months)
- Adherence to treatment measured with Morisky Green Scale (MMAS).(at 6 and at 12 months)
- 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(12 months)
- Quality of Life perceived by the patient, measured with EQ-5D-5L questionnaire.(baseline and at 12 months)