Clinical trial NCT04033276: IVIG/Rituximab vs Rituximab in Kidney Transplant With de Novo Donor-specific Antibodies
Official title: A Randomized, Open, Controlled Trial of High Dose IVIG/Rituximab Versus Rituximab in Kidney Transplant Patients With de Novo Donor-specific Antibodies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Renal Transplant
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Severance Hospital
name: GC Biopharma Corp
First posted: 2019-07-26
Enrollment: 50
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The objective of this study was to compare two strategies of de novo donor specific antibodies (DSA) and antibody-mediated rejection (AMR) prevention in renal transplant recipients: high dose intravenous immunoglobulin (IVIG)/rituximab regimens versus rituximab alone.

Detailed description: Although recent advances in immunosuppressive regimens after kidney transplantation (KT) have reduced the incidence and consequences of T-cell-mediated rejection (TCMR) and have improved short-term outcomes, long-term allograft loss attributable to AMR is still responsible for substantial medical and socioeconomic burdens in kidney transplant recipients. Numerous studies have shown that de novo DSA after KT are associated with AMR, which leads to allograft loss. IVIG is a medication that has emerged as a useful tool in modulating immunity, treatment of AMR and in desensitization protocol. Treatment with rituximab or combination of IVIG/rituximab has sought to further diminish antibody production (de novo DSA) in the treatment of AMR. Several studies have been reported, but in the absence of control groups or standardization of treatment, their efficacy is difficult to assess.

Eligibility criteria: Inclusion Criteria:

All patients have de novo production of DR or DQ DSA after renal transplantation Inclusion criteria requires all of the following

1. age ≥ 19 years
2. Renal transplants with eGFR ≥ 20 ml/min (by CKD-EPI equation) and change in the eGFR ≤ 20 within 3 months
3. No history of biopsy proven acute T cell mediated rejection or antibody-mediated rejection within 3 months
4. peak MFI of de novo DSA (DR or DQ) ≥ 1000
5. A patient who agree to write a written consent form

Exclusion Criteria:

1. age ≤ 18 years
2. multi-organ transplantation
3. Patients with no history of tacrolimus as immunosuppressants
4. history of allergic or anaphylactic reaction to rituximab
5. human immunodeficiency virus infection
6. active infection
7. pregnancy or lactation
8. history of drug abuse or alcohol abuse within 6 months
9. history of malignancy within 5 years
10. history of treatment for psychiatric problems
11. hematologic or biochemical abnormalities (Hb \< 7g/dL, Platelet \< 1x105/mm3, AST/ALT \> 80IU)
12. A patient who do not want to participate in this study

Primary outcomes:
measure: change in delta DSA MFI sum
timeFrame: baseline and 3 months post-treatment, 1 year post-treatment
Secondary outcomes:
measure: Change in estimated glomerular filtration rate(eGFR) by CKD-EPI equation
timeFrame: baseline and 3 months post-treatment, 1 year post-treatment
measure: Development of antibody-mediated rejection (AMR)
timeFrame: up to 1 year post-treatment
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
Study officials:
affiliation: Seoul National University Hospital
name: Jaeseok Yang, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: