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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PE/rATG | Placebo Comparator | 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). |
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| PE/rATG/IVIG | Active Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Privigen | Drug | Patients randomized to PE/rATG/IVIG group will receive IVIG 0.5g/kg infusions, on 1st, 3rd and 5th postoperative day. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 12 months |
| Time to active antibody-mediated rejection (ABMR) within 12 months post-transplantation |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ondrej Viklicky, Prof. | Institute for Clinical and Experimental Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute for Clinical and Experimental Medicine | Prague | 140 21 | Czechia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40458542 | Derived | 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. |
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The present study is a prospective randomized single-centre open-label two-arm Phase III.b non-inferiority clinical trial. This trial aims to prove similar efficacy of PE/rATG 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.
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| Thymoglobulin | 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. |
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| Plasma Exchange | Other | All patient will undergo Plasma Exchange before transplantation. |
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Time to active antibody-mediated rejection (ABMR) occurrence in months |
| 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 | 3 and 12 months |
| Incidence of transplant glomerulopathy (TG) in protocol biopsies at Month 3 and Month 12 | Number of biopsies with transplant glomerulopathy | 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 | 3 and 12 months |
| Estimated glomerular filtration rate (eGFR) at Month 3, Month 6 and Month 12 | Estimated glomerular filtration rate (eGFR) will be assessed at all study visits by CKD-EPI formula. | 3, 6 and 12 months |
| Measured proteinuria and albuminuria at Month 3, Month 6 and Month 12 | Proteinuria is defined as ≥ 1 g/l and albuminuria as albumin/creatinine ratio > 3 mg/mmol. | 3, 6 and 12 months |
| Donor specific antibodies (DSA) at Month 3, Month 6 and Month12 | Specification of antibodies directed at HLA class I and class II will be performed by LUMINEX method (solid phase assay). | 3, 6 and 12 months |
| De novo donor specific antibodies (DSA) at Month 3, Month 6 and Month 12 | Specification of antibodies directed at HLA class I and class II will be performed by LUMINEX method (solid phase assay). | 3, 6 and 12 months |
| Mortality rate within 12 months post-transplantation | Number of deaths by any cause anytime during the trial. | 12 months |
| Graft survival (rate of graft loss) within 12 months post transplantation | Number graft of graft failures within 12 months | 12 months |
| Incidence of metabolic, malignant and cardiovascular co-morbidities | Number of metabolic, malignant and cardiovascular co-morbidities | 12 months |
| Incidence of viral and bacterial complications | Number of viral and bacterial complications | 12 months |
| Incidence of BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) replications detected by PCR (polymerase chain reaction) at Month 3, Month 6 and Month 12 | Number of patients with PCR (polymerase chain reaction) positive BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) replications | 3, 6 and 12 months |
| Incidence of study treatment discontinuation | Cessation of trial medication treatment either by the clinician or by the participant himself/herself. | 12 months |
| Incidence of molecular rejection in the 12-month protocol biopsies | Number of molecular rejection cases evaluated by the Molecular Microscope Diagnostic System (MMDx) in the 12-month protocol biopsies. | 12 months |
| ID | Term |
|---|---|
| D016756 | Immunoglobulins, Intravenous |
| C512542 | thymoglobulin |
| D010951 | Plasma Exchange |
| ID | Term |
|---|---|
| D007074 | Immunoglobulin G |
| D007132 | Immunoglobulin Isotypes |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D001803 | Blood Transfusion |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D010956 | Plasmapheresis |
| D001781 | Blood Component Removal |
| D016060 | Sorption Detoxification |
| D005112 | Extracorporeal Circulation |
| D013514 | Surgical Procedures, Operative |
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