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

NCT ID: NCT04302805

Last Updated: 2024-08-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-27
• Study Completion Date: 2024-06-15

Brief Summary

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.

Detailed 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.

Conditions

Kidney Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

PE/rATG

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).

Group Type: PLACEBO_COMPARATOR

Thymoglobulin

Intervention Type: DRUG

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 Exchange

Intervention Type: OTHER

All patient will undergo Plasma Exchange before transplantation.

PE/rATG/IVIG

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.

Group Type: ACTIVE_COMPARATOR

Privigen

Intervention Type: DRUG

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

Thymoglobulin

Intervention Type: DRUG

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 Exchange

Intervention Type: OTHER

All patient will undergo Plasma Exchange before transplantation.

Interventions

Privigen

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

Intervention Type: DRUG

Thymoglobulin

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.

Intervention Type: DRUG

Plasma Exchange

All patient will undergo Plasma Exchange before transplantation.

Intervention Type: OTHER

Other Intervention Names

IVIG; Kiovig; rATG; PE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute for Clinical and Experimental Medicine

OTHER_GOV

Sponsor Role: lead

Responsible Party

Prof. Ondřej Viklický, M.D., Ph.D.

Head of Department of Nephrology and Transplant Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ondrej Viklicky, Prof.

Role: PRINCIPAL_INVESTIGATOR

Institute for Clinical and Experimental Medicine

Locations

Institute for Clinical and Experimental Medicine

Prague, , Czechia

Countries

Czechia

References

Viklicky O, Zahradka I, Mares J, Slatinska J, Parikova A, Petr V, Roder M, Jaklova K, Osickova K, Janousek L, Hruba P. 12-Month Outcomes of a Prospective Randomized Trial Investigating Effects of IVIG on Top of rATG Versus rATG Alone in Pre-Sensitized Kidney Transplant Recipients: The INHIBIT Study. Transpl Int. 2025 May 19;38:14312. doi: 10.3389/ti.2025.14312. eCollection 2025.

Reference Type: DERIVED

PMID: 40458542 (View on PubMed)

Other Identifiers

Eudra CT: 2019-003723-37

Identifier Type: -

Identifier Source: org_study_id