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

Institute for Clinical and Experimental Medicine

Status and phase: Completed; Phase 3

Conditions: Kidney Transplantation

Treatments: Other: Plasma Exchange; Drug: Privigen; Drug: Thymoglobulin

Study type: Interventional

Funder types: Other

Identifiers

NCT04302805

Eudra CT: 2019-003723-37

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 17 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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17 participants in 2 patient groups, including a placebo group

PE/rATG

Placebo Comparator group

Description:

Study participants will undergo therapeutic plasma exchange (PE, 1 plasma volume) before the transplant surgery and receive rATG (Thymoglobuline®) induction (1.5 mg/kg intraoperatively and 1 mg/kg when possible daily within first week up to cumulative dose 5-7 mg/kg).

Treatment:

Drug: Thymoglobulin

Other: Plasma Exchange

PE/rATG/IVIG

Active Comparator group

Description:

Study participants will undergo therapeutic plasma exchange (PE, 1 plasma volume) before the transplant surgery and receive rATG (Thymoglobuline®) induction (1.5 mg/kg intraoperatively and 1 mg/kg when possible daily within first week up to cumulative dose 5-7 mg/kg) and IVIG 0.5g/kg intravenous infusions, on 1st, 3rd and 5th postoperative day. This is a center standard of care regimen.

Treatment:

Drug: Thymoglobulin

Drug: Privigen

Other: Plasma Exchange