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

Kidney Transplantation Clinical Trial

— INHIBIT  

Official title:

rATG Versus rATG Combined With IVIG Induction Immunosuppression in HLA Incompatible Transplantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04302805
• Other study ID #: Eudra CT: 2019-003723-37
• Status: Recruiting
• Phase: Phase 3
• Start date: July 27, 2020
• Est. completion date: April 15, 2024

Study information

• Verified date: March 2024
• Source: Institute for Clinical and Experimental Medicine
• Contact: Ondrej Viklicky, Prof.
• Phone: +420 261364110
• Email: ondrej.viklicky[@]ikem.cz
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 138
• Est. completion date: April 15, 2024
• Est. primary completion date: April 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

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

Other:
• Plasma Exchange
All patient will undergo Plasma Exchange before transplantation.

Locations

Country	Name	City	State
Czechia	Institute for Clinical and Experimental Medicine	Prague

Sponsors (1)

Lead Sponsor	Collaborator
Institute for Clinical and Experimental Medicine

Country where clinical trial is conducted

Czechia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	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
Secondary	Time to active antibody-mediated rejection (ABMR) within 12 months post-transplantation	Time to active antibody-mediated rejection (ABMR) occurrence in months	12 months
Secondary	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
Secondary	Incidence of transplant glomerulopathy (TG) in protocol biopsies at Month 3 and Month 12	Number of biopsies with transplant glomerulopathy	3 and 12 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Mortality rate within 12 months post-transplantation	Number of deaths by any cause anytime during the trial.	12 months
Secondary	Graft survival (rate of graft loss) within 12 months post transplantation	Number graft of graft failures within 12 months	12 months
Secondary	Incidence of metabolic, malignant and cardiovascular co-morbidities	Number of metabolic, malignant and cardiovascular co-morbidities	12 months
Secondary	Incidence of viral and bacterial complications	Number of viral and bacterial complications	12 months
Secondary	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
Secondary	Incidence of study treatment discontinuation	Cessation of trial medication treatment either by the clinician or by the participant himself/herself.	12 months