Induction in Sensitized Kidney Transplant Recipients Without Pre-existing Donor-specific antiboDies

NCT05385432 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: DR210298 - INSTEAD
• Study Type: interventional
• Target: 244
• Locations: 0 countries
• Sites: N/A

Brief Summary

Induction therapy decreases the rate of acute allograft rejection in kidney transplant recipients (KTRs) and is strongly recommended. Polyclonal lymphocyte-depleting antibodies and interleukin-2 receptor (IL2R) antagonists are therefore widely used around the world, with a leading position for rabbit anti-thymocyte globulin (rATG, Thymoglobulin®) and basiliximab (Simulect®), respectively. The actual immunological risk of the sensitized KTRs without donor specific antibodies (DSAs) is still debated. The benefit-risk equation of lymphocyte depleting antibodies (versus IL2R antagonists) is not known in sensitized KTRs without DSAs. This clinical trial will compare the efficacy and safety of basiliximab and rATG in sensitized KTR without pre-existing DSAs detected by Luminex.

Conditions

Renal Transplant Rejection; Induction Therapy

Keywords

Kidney transplantation; Basiliximab; ATG; induction; rejection

Outcome Measures

Primary Outcomes (1)

• Incidence of biopsy-proven acute rejection (BPAR) at year 1

  Incidence of BPAR (treated suspicious TCMR and confirmed TCMR with grade ≥ 1 and ABMR) in rATG and basiliximab groups, determined after blind central reading according to Banff 2019 classification.

  during the first post-transplantation year

Secondary Outcomes (10)

• Incidence of BPAR in rATG and basiliximab groups at year 3.

  at year 3

• Incidence of composite criteria

  at year 3

• Incidence of confirmed TCMR and ABMR in rATG and basiliximab groups at year 1 and 3.

  at year 1 and 3

• Incidence of de novo DSA in rATG and basiliximab groups at year 1 and 3

  at year 1 and 3

• Incidence of CMV viremia, CMV disease, BKv viremia and BKv nephropathy in rATG and basiliximab groups at year 1 and 3.

  at year 1 and 3

Study Arms (2)

rabbit antithymocyte globulin (rATG)

EXPERIMENTAL

The infusion of rATG (Thymoglobulin® (1.5mg/kg/day, maximum daily dose: 100 mg)) starts just after the randomization pre-operatively on a functional arteriovenous fistula or a high-flow venous catheter during 3 to 7 days until efficient tacrolimus level is obtained. The recommended initial tacrolimus dose is Prograf® 0.1mg/kg/day twice day.

Drug: Rabbit Anti thymocyte globulin (rATG)

Basiliximab

ACTIVE COMPARATOR

The infusion of Basiliximab (Simulect® (20mg)) starts before the surgery on peripheral vein for 15 minutes and the second infusion at day 4.

Drug: Basiliximab

Interventions

Rabbit Anti thymocyte globulin (rATG) DRUG

The infusion of rTAG (Thymoglobulin® (1.5mg/kg/day, maximum daily dose: 100 mg)) starts just after the randomization pre-operatively on a functional arteriovenous fistula or a high-flow venous catheter during 3 to 7 days until efficient tacrolimus level is obtained.

Also known as: Maintenance immunosuppressive regimen is the same in experimental and control groups combining tacrolimus, mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS) and steroids

rabbit antithymocyte globulin (rATG)

Basiliximab DRUG

Simulect® IV 40mg D0 and D4

Also known as: Maintenance immunosuppressive regimen is the same in experimental and control groups combining tacrolimus, mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS) and steroids

Basiliximab

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged between 18-79
• Registered on the transplant waiting list
• At least one anti-HLA antibody identified by the Luminex Single Antigen test with MFI ≥ 2000 (MFI threshold in agreement with French kidney allocation system.)
• Graft incompatibility rate (TGI) \< 85%
• Ability for participant to comply with the requirements of the study
• Written informed consent obtained from the participant
• Participants covered by or entitled to social security.

You may not qualify if:

• DSA (negative virtual crossmatch with MFI threshold at 1000)
• Combined transplantation
• Usual contraindications to a kidney transplantation such as morbid obesity (BMI \> 40 kg/m2), active drug abuse, uncontrolled psychiatric disease, or decompensated heart failure
• Beneficiaries of kidney transplants from donations after uncontrolled circulatory death (Maastricht II)
• Incompatible ABO transplantation
• Leukopenia lower than 3000/mm3
• Thrombocytopenia (platelets \< 50G/L)
• Donor EBV Positive / Recipient EBV Negative
• Active HIV infection (positive viral charge)
• History of solid cancer (\< 5 years), except to skin carcinoma (squamous-cell and basal-cell carcinoma).History of some solid cancer (prostate, breast) can be reduced (\<2 years), depending on the prognosis for cancer recurrence as assessed by the oncologist.
• History of lymphoma
• Patients with severe uncontrolled systemic infection or severe allergy requiring acute or chronic treatment; Aspartate aminotransferase (ASAT), Alanine Amino Transferase (ALAT) or bilirubin greater than 3 times normal
• Known hypersensitivity or contra-indication to rabbit proteins, basiliximab including the product excipients
• Contra-indication to tacrolimus,mycophenolic acid ans steroids
• Patient under judicial protection, deprivation of liberty

Sponsors & Collaborators

• University Hospital, Tours: lead

Related Publications (2)

• Goumard A, Sautenet B, Bailly E, Miquelestorena-Standley E, Proust B, Longuet H, Binet L, Baron C, Halimi JM, Buchler M, Gatault P. Increased risk of rejection after basiliximab induction in sensitized kidney transplant recipients without pre-existing donor-specific antibodies - a retrospective study. Transpl Int. 2019 Aug;32(8):820-830. doi: 10.1111/tri.13428. Epub 2019 Apr 12.

  PMID: 30903722 RESULT

• Wajih Z, Karpe KM, Walters GD. Interventions for BK virus infection in kidney transplant recipients. Cochrane Database Syst Rev. 2024 Oct 9;10(10):CD013344. doi: 10.1002/14651858.CD013344.pub2.

  PMID: 39382091 DERIVED

MeSH Terms

Conditions

Rejection, Psychology

Interventions

Antilymphocyte Serum; Mycophenolic Acid; Steroids; Basiliximab

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Fused-Ring Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2022
• First Posted: May 23, 2022
• Study Start: September 12, 2023
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2030
• Last Updated: September 5, 2023

Record last verified: 2023-09