Clinical trial NCT03465397: Individualization of the Immunological Risk Based on Selective Biomarkers in Living-donor Renal Recipients
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Kidney Transplant Failure and Rejection
Lead sponsor: Hospital Universitari de Bellvitge
Sponsor class: OTHER
Collaborators: name: Department of Health, Generalitat de Catalunya
First posted: 2018-03-14
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter open clinical trial, randomized, stratified by age, parallel groups
Primary purpose: PREVENTION

Brief summary: 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: composite
timeFrame: 24 months
Secondary outcomes:
measure: mortality
timeFrame: 24 months
measure: kidney graft loss
timeFrame: 24 months
measure: Subclinical and chronic rejection
timeFrame: at 3 and 24 months
measure: Opportunistic infections
timeFrame: 24 months
measure: Metabolopathies
timeFrame: 24 months
measure: Cardiovascular Events
timeFrame: 24 months
measure: Malignancy
timeFrame: 24 months
measure: Treatment maintenance
timeFrame: 24 months
measure: Immune Response Changes
timeFrame: 24 months
measure: Economic cost
timeFrame: 24 months
measure: Serious adverse reactions
timeFrame: 24 months
Other outcomes:
Locations:
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Fundació Puigvert
city: Barcelona
country: Spain
facility: Hospital Clinic
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D'Hebrón
Study officials:
References: