Individualization of the Immunological Risk Based on Selective Biomarkers in Living-donor Renal Recipients (BIOIMMUN)

Multicenter, Randomized Study to Evaluate the Effectiveness of the Individualization of the Immunological Risk Based on Biomarkers (Disparity of HLA and IFN-γ ELISPOT) to Optimize Immunosuppressor Treatment in Living-donor Renal Recipients

This is a clinical trial comparing the immunosuppressive treatment determined according to two biomarkers, donor-specific IFN-γ ELISPOT and Mismatch of HLA between donor and recipient, in patients undergoing low immunological risk live donor kidney transplantation

Study Overview

• Status: Unknown
• Conditions: Kidney Transplant Failure and Rejection
• Intervention / Treatment: Diagnostic test: biomarkers driven immunosuppressive therapy

Detailed Description

This is a national multicenter clinical trial, controlled, randomized, stratified, parallel groups, and without masking.

This is a prospective intervention study in which two strategies for determining immunosuppressive treatment in kidney transplant patients from a live donor with low immunological risk are compared according to solid phase antibody detection techniques (cPRA 0% and isolated negative antigen) and crossmatch by negative cytotoxicity. Patients are randomized in a 1: 1 ratio to receive one of two immunosuppressive treatment strategies.

• Study Type: Interventional
• Enrollment (Anticipated): 164
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Badalona, Spain
    • Recruiting
    • Hospital Universitari Germans Trias i Pujol
    • Contact: RICARDO LAUZURICA, DR; Email: rlauzurica.germanstrias@gencat.cat
    • Contact: LAURA CAÑAS, DR; Email: laucanyas78@hotmail.com
    • Principal Investigator: RICARDO LAUZURICA
    • Principal Investigator: LAURA CAÑAS
  • Barcelona, Spain
    • Recruiting
    • Hospital Universitari Vall d'Hebron
    • Contact: FRANCESC MORESO, DR
    • Contact: Email: fjmoreso@vhebron.net
    • Principal Investigator: FRANCESC MORESO, DR
  • Barcelona, Spain
    • Recruiting
    • Hospital del Mar
    • Contact: MARTA CRESPO, DR; Email: MCrespo@parcdesalutmar.cat
    • Principal Investigator: MARTA CRESPO, DR
  • Barcelona, Spain
    • Not yet recruiting
    • Hospital Clinic
    • Contact: FRITZ DIEKMANN, DR; Email: FDIEKMAN@clinic.cat
    • Principal Investigator: FRITZ DIEKMANN, DR
  • Barcelona, Spain
    • Recruiting
    • Fundacio Puigvert
    • Contact: CARME FACUNDO, DR; Email: CFacundo@fundacio-puigvert.es
    • Principal Investigator: LLUIS GUIRADO, DR
    • Principal Investigator: CARME FACUNDO, DR
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Recruiting
      • Hospital Universitari de Bellvitge
      • Contact: Carolina Polo, PhD; Phone Number: +34 93 260 73 85; Email: cpolo@idibell.cat
      • Contact: Eulàlia Molinas; Phone Number: +34 93 260 73 85; Email: emolinas@idibell.cat
      • Principal Investigator: ORIOL BESTARD, DR
      • Sub-Investigator: EDOARDO MELILLI, DR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult men and women (≥18 years).
2. Receptors of a first kidney transplant from an incompatible HLA living donor (at least 1 mismatch HLA at any antigenic level).
3. AB0 compatible transplant.
4. Patients with a calculated PRA of 0% by solid phase technique and absence of anti-HLA class I and class II antibodies by single antigen test (Luminex®).
5. Patients who agree to participate in the Trial by signing the Specific Informed Consent of this study.
6. Potentially fertile women should use high reliability contraceptive methods (Pearl-Index <1) in order to avoid pregnancy during the entire duration of the study and up to 6 weeks after the end of their treatment with Mycophenolate Mofetil (MMF). Potentially Fertile Women include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or who is not post-menopausal (defined as amenorrhea ≥ 12 consecutive months, or women who are receiving hormone replacement therapy with a documented level of follicle stimulating hormone (FSH)> 35 mlU / ml). Potentially fertile women must have a pregnancy test with a negative result in the 72 hours prior to the start of the trial.
7. Sexually active males (including vasectomized males) who are being treated with MMF must accept the use of barrier contraceptive methods during MMF treatment and for 90 days thereafter. Potentially fertile partners of these patients should use a reliable contraceptive method during the same period, in order to minimize the risk of pregnancy.
8. Patients must agree not to donate blood during treatment with MMF and during the 6 subsequent weeks. Males should not make a sperm donation during MMF treatment and up to 90 days after completion.

Exclusion Criteria:

1. Patients with a calculated PRA higher than 0% per solid phase and / or anti-HLA class I and / or class II antibodies detectable by single antigen test (Luminex®).
2. Positive result of Cross Match.
3. Patients who receive a graft from a cadaver donor.
4. Identical HLA patients
5. Patients who have undergone a previous solid organ transplant (including kidney transplant) or who are going to receive another solid organ transplant concomitantly.

6. Patients with any of the following basic renal diseases:

   • Glomerular primary focal and segmental sclerosis
   • Atypical hemolytic uremic syndrome (aHUS) / thrombotic thrombocytopenic purpura syndrome.
7. Patients with chronic infection with Hepatitis B virus (HBV) and / or active infection with Hepatitis C virus (positive PCR result) at the time of transplant.
8. Patients with infection with the known Human Immunodeficiency Virus (HIV).
9. Patients with active systemic infection that requires the continued administration of antibiotics.
10. Patients with any neoplasm except localized skin cancer and who is receiving adequate treatment.
11. Patients with severe anemia (hemoglobin <6g / dl), leukopenia (WBC <2500 / mm3) and / or thrombocytopenia (platelets <80,000 / mm3).
12. Patients who are hemodynamically unstable even if they have hemoglobin levels> 6g / dL.
13. Patients with intestinal pathology or severe diarrhea that may decrease absorption according to medical criteria.
14. Patients with known hypersensitivity to any of the drugs used in this study.
15. Patients who have received any investigational drug in the 30 days prior to their inclusion in this study.
16. Potentially fertile women who do not agree to use reliable contraceptive measures during the trial, who are pregnant, breastfeeding or who present a positive pregnancy test at the time of their inclusion in the study.
17. Patients who are legally detained in an official institution.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: experimental; Biomarkers driven immunosuppressive therapy: the immunosuppressive treatment of the patients is determined according to the result of 2 biomarkers of immunological risk	Diagnostic test: biomarkers driven immunosuppressive therapy; the immunosuppressive treatment of the patients is determined according to the result of 2 biomarkers of immunological risk
NO_INTERVENTION: control; All patients receive the usual triple immunosuppressive treatment, without depending on the results of any biomarker.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
composite	composite variable evaluated at 2 years of follow-up as a proportion of patients who meet any of the following criteria: loss of renal function, incidence of acute clinical rejection confirmed by biopsy (BPAR) and development of dnDSA.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mortality	Mortality from any cause	24 months
kidney graft loss	Loss of kidney graft	24 months
Subclinical and chronic rejection	Incidence and severity of subclinical and chronic rejection (according to protocol biopsies)	at 3 and 24 months
Opportunistic infections	Incidence of opportunistic infections	24 months
Metabolopathies	Incidence of metabolopathies derived from the treatment (diabetes mellitus, dyslipidemia and HT)	24 months
Cardiovascular Events	Incidence of cardiovascular events	24 months
Malignancy	Incidence of malignancy (cutaneous and non-cutaneous cancer)	24 months
Treatment maintenance	Proportion of patients who maintain the treatment according to the protocol at the end of the trial.	24 months
Immune Response Changes	Changes in the immune response at 24 months according to the biomarkers (urine cytokines CXCL9 and CXCL10, test KSORT, ELISPOT)	24 months
Economic cost	Study of the economic cost	24 months
Serious adverse reactions	serious adverse events with a possible causal relationship with the immunosuppressive treatment)	24 months

Collaborators and Investigators

• Sponsor: ORIOL BESTARD
• Collaborators: Department of Health, Generalitat de Catalunya

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 10, 2017
• Primary Completion (ANTICIPATED): November 1, 2021
• Study Completion (ANTICIPATED): November 1, 2021

Study Registration Dates

• First Submitted: January 4, 2018
• First Submitted That Met QC Criteria: March 13, 2018
• First Posted (ACTUAL): March 14, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 8, 2021
• Last Update Submitted That Met QC Criteria: January 7, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Immunosuppressive Agents
• Other Study ID Numbers: BIOIMMUN

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No