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

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.

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