rATG Versus rATG Combined With Intravenous Immunoglobulin (IVIG) Induction Immunosuppression in HLA Incompatible Transplantation (INHIBIT)

Institute for Clinical and Experimental Medicine17 enrolled

Overview

This study aims to prove similar efficacy of PE/rATG (intervention) and PE/rATG/IVIG (centre standard of care) induction regimens to prevent biopsy proven antibody-mediated changes and TCMR as composite endpoint within 12 months after HLA incompatible kidney transplantation.

There have been no published clinical studies evaluating rATG/IVIG induction protocol in comparison with rATG alone in defined cohort of HLA incompatible kidney transplant recipients. Prescribing IVIG in management of prevention of transplant rejection is considered off-label use, however IVIG remains part of induction protocols in many transplant centres. IVIG therapy is demanding due to high cost and limited resources of these human origin products. Trial participants will be end-stage renal disease (ESRD) patients listed for deceased donor / living donor kidney transplantation with anti HLA antibody screening performed within 12 months before transplantation and with last DSA 1 000 - 5 000 Mean Fluorescence Intensity (MFI) and negative CDC (Complement-dependent cytotoxicity crossmatch test) prior to transplantation. Participants will be randomized into one of the treatment groups (PE/PP(Plasmapheresis) + rATG + IVIG, PE/PP + rATG) and as a primary outcome a composite endpoint defined as occurrence of antibody- or T-cell mediated rejection within 12 months after transplantation will be evaluated.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Kidney Transplantation

Interventions

PrivigenDRUG

Patients randomized to PE/rATG/IVIG group will receive IVIG 0.5g/kg infusions, on 1st, 3rd and 5th postoperative day.

ThymoglobulinDRUG

All patients will receive 1.5 mg/kg intraoperatively and 1 mg/kg when possible daily within first week up to cumulative dose 5-7 mg/kg.

Plasma ExchangeOTHER

All patient will undergo Plasma Exchange before transplantation.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Primary deceased donor or living donor kidney transplantation (first transplantation or re-transplantation) * Recipient age ≥ 18 years and \< 70 years * Donor age \< 70 years * Written Informed Consent and Consent for Processing Personal Data * Last anti-HLA screening no longer than 12 months with positive results * MFI DSA 1 000 - 5 000 (anti-HLA A, B, DR), MFI DSA 1000-15000 for anti DQ when available at randomization) Exclusion Criteria: * Combined kidney transplantation with another organ * Immunosuppressive therapy up to 6 months before transplantation * AB0i (AB0 incompatible) transplantation * Women in childbearing potential without adequate contraception * HIV positivity * Leukopenia \< 3 000, thrombocytopenia \< 75 000 * Tuberculosis history * Anti-HCV (Hepatitis C Virus) positivity, HBsAg (Hepatitis B Surface Antigen) positivity or HBV (Hepatitis B Virus) DNA positivity * DSA (anti A, B, DR) measured by Luminex with MFI \> 5 000 known at screening prior to transplant, anti DQ \> 15000 if known * FACS (flow-cytometry) T and B crossmatch positivity known at screening prior to transplant * Positive CDC prior to transplantation * Planned PP/PE and RTX (Rituximab) treatment post-transplant * Advanced liver disease (Child-Pugh C or laboratory values of ALT or AST more than 3 times upper limit of normal range) * Pregnancy, breastfeeding * Study medication is contraindicated according to the SmPC * Patient is enrolled in other clinical trial

Locations (1)

Institute for Clinical and Experimental Medicine

Prague, Czechia

Outcomes

Primary Outcomes

Combined endpoint defined as biopsy proven antibody mediated changes (Banff 2017, Category 2) and/or TCMR (Banff 2017, Category 4) regardless the biopsy indication (for cause or protocol biopsy) in HLAi (HLA incompatible)kidney transplantation

Number of biopsy-confirmed rejections

Time frame: 12 months

Secondary Outcomes

Incidence of active antibody-mediated rejection (ABMR) lesions within 12 months post-transplantation

Number of active active antibody-mediated rejection (ABMR) lesions within 12 months post-transplantation

Time frame: 12 months

Time to active antibody-mediated rejection (ABMR) within 12 months post-transplantation

Time to active antibody-mediated rejection (ABMR) occurrence in months

Time frame: 12 months

Incidence of chronic active antibody-mediated rejection (ABMR) and C4d staining without evidence of rejection in protocol biopsies at Month 3 and Month 12

Number of chronic active antibody-mediated rejection (ABMR) and C4d staining without evidence of rejection in protocol biopsies at Month 3 and Month 12

Time frame: 3 and 12 months

Incidence of transplant glomerulopathy (TG) in protocol biopsies at Month 3 and Month 12

Number of biopsies with transplant glomerulopathy

Time frame: 3 and 12 months

Incidence of acute T-cell mediated rejection (TCMR) and chronic active TCMR in protocol biopsies at Month 3 and Month 12 post-transplantation

Number of acute T-cell mediated rejection (TCMR) and chronic active TCMR in protocol biopsies at Month 3 and Month 12

Time frame: 3 and 12 months

Data from ClinicalTrials.gov

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