IVIG/Rituximab vs Rituximab in Kidney Transplant With de Novo Donor-specific Antibodies

Study Overview
=================
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.

Official Title
-----------------
A Randomized, Open, Controlled Trial of High Dose IVIG/Rituximab Versus Rituximab in Kidney Transplant Patients With de Novo Donor-specific Antibodies

Conditions
-----------------
Renal Transplant

Intervention / Treatment
-----------------
* Drug: Rituximab
* Drug: intravenous immune globulin


Participation Criteria
=================
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 age ≥ 19 years Renal transplants with eGFR ≥ 20 ml/min (by CKD-EPI equation) and change in the eGFR ≤ 20 within 3 months No history of biopsy proven acute T cell mediated rejection or antibody-mediated rejection within 3 months peak MFI of de novo DSA (DR or DQ) ≥ 1000 A patient who agree to write a written consent form Exclusion Criteria: age ≤ 18 years multi-organ transplantation Patients with no history of tacrolimus as immunosuppressants history of allergic or anaphylactic reaction to rituximab human immunodeficiency virus infection active infection pregnancy or lactation history of drug abuse or alcohol abuse within 6 months history of malignancy within 5 years history of treatment for psychiatric problems hematologic or biochemical abnormalities (Hb < 7g/dL, Platelet < 1x105/mm3, AST/ALT > 80IU) A patient who do not want to participate in this study

Ages Eligible for Study
-----------------
Minimum Age: 19 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rituximab<br>Inj Rituximab 375mg/m2 IV given on day 0 | Drug: Rituximab<br>* IV rituximab<br>* Other names: mabthera;|
| Active Comparator: Combination of high-dose IVIG and Rituximab<br>IV Rituximab 375mg/m2 on day 0 and IV high-dose IVIG 2g/kg on day 0 | Drug: Rituximab<br>* IV rituximab<br>* Other names: mabthera;Drug: intravenous immune globulin<br>* iv intravenous immune globulin<br>* Other names: IVIG-SN;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in delta DSA MFI sum | change of pre- and post-treatment DSA MFI sum, monitoring DSA during follow-up period | baseline and 3 months post-treatment, 1 year post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in estimated glomerular filtration rate(eGFR) by CKD-EPI equation | change of pre- and post-treatment eGFR by CKD-EPI equation, monitoring eGFR during follow-up period | baseline and 3 months post-treatment, 1 year post-treatment | 
| Development of antibody-mediated rejection (AMR) | To identify the development of AMR after treatment during follow-up period | up to 1 year post-treatment |