Basiliximab vs Low-dose Thymoglobulin Induction Therapy in Low Risk Kidney Transplant Patients

Basiliximab vs Reduced Dose Rabbit Antithymocyte Globulin (rRTAG): Evaluation of Efficacy and Safety Outcomes in Low Immunological Risk Living Donor Kidney Transplant: 12-month Randomized Controlled Study

Demonstrate that low dose (3 mg/kg total ) rATG (thymoglobulin) has similar efficacy (delayed graft function, slow graft function, biopsy proven acute rejection episodes, infections, hospitalizations, adverse events, graft loss and death) than Basiliximab induction

Study Overview

• Status: Completed
• Conditions: Kidney Transplant Rejection; Kidney Transplant; Complications
• Intervention / Treatment: Drug: Basiliximab; Drug: Thymoglobulin

Detailed Description

Introduction: The TAILOR study in living donor kidney transplantation demonstrated a 98% one year patient and graft survival and 91% and 83% at 5 years with rejection-free patients in 93%. The cumulative dose of r ATG (thymoglobulin) was 5.29 mg / kg with 3% adverse effects and almost 50% steroid free at 12 months. Others have explored the benefit of low doses of r ATG (thymoglobulin) (3-5 mg / kg) against Basiliximab in low-risk population and demonstrated in living donor recipients with 8 year follow-up similar survival rates with a lower BPAR rate in rATG (thymoglobulin) (p <0.05) and better serum creatinine in 3 and 5 years. The aim of the study was to demonstrate that low dose (3 mg/kg total ) rATG (thymoglobulin) has similar efficacy (delayed graft function, slow graft function, biopsy proven acute rejection episodes, infections, hospitalizations, adverse events, graft loss and death) than Basiliximab induction.

Material and methods: Prospective randomized study of patients undergoing renal transplantation who wish to participate. 100 patients who meet the inclusion and exclusion criteria at the time of transplantation will be randomized

Experimental and reference therapy:

Group A: Induction with Basiliximab 20 mg IV day 0 and day 4 Group B: rATG (Thymoglobulin) 1 mg / kg body weight per day for days 0, 1 and 2 up to a total dose of 3 mg / kg day. According to protocol administration, if there are conditions to delay administration (WBC<2000 / mm3 and / or platelets <75,000 / mm3) (17), administration may be postponed until day 7 posttransplant Posttransplant immunosuppression: Tacrolimus, mycophenolate mofetil and steroids

Outcome measures (12 months) delayed graft function slow graft function biopsy proven acute rejection episodes infections hospitalizations adverse events graft loss death

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• Mexico
  • Veracruz, Mexico, 91897
    • Umae Hospital Especialidades 14 Adolfo Ruiz Cortines

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female graft recipients older than 18 years of age.
• Informed consent to participate in the study.
• First living donor kidney transplant recipient.
• Negative pregnancy test if female participant

Exclusion Criteria:

• Second or more kidney transplant.
• Multiple organ transplant recipients.
• ABO incompatibility or positive cross-over test prior to transplantation.
• Antibody Reactive Panel (PRA) > 30%.
• Positive specific donor antibodies (DSA).
• Human immunodeficiency virus (HIV) positive patients.
• HBsAg or HCV positive.
• Severe lung disorders.
• Severe allergies receiving treatment that prevent patient's rRTAG administration.
• Leukocyte count below 2000 / mm3.
• Platelet count below 75,000 / mm3.
• History of malignant disease of any organ system (except skin basal cell carcinoma) within the last 5 years, regardless of local recurrence or metastasis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A (Basiliximab group); Basiliximab (Simulect) induction therapy: 20 mg IV at day of transplant (to be administered 2 hours prior to transplant and up to 4 hours after transplant) and second dosage (20 mg) at fourth day after kidney transplantation.	Drug: Basiliximab; Standard induction therapy; Other Names: Simulect
Experimental: B (Low-dose Thymoglobulin group); Thymoglobulin induction therapy (1 mg/kg rounded by 25 mg increments) at day of transplant followed by same dosage (1 mg/kg rounded by 25 mg increments) during day 1 and day 2 after transplant in order to complete 3 mg/kg accumulated dose.	Drug: Thymoglobulin; Induction therapy; Other Names: rATG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biopsy proven acute rejection	Acute rejection described by Banff category	12 months following transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delayed graft function	Dialysis during first week of transplantation	12 months following transplantation
Slow graft function	Creatinine clearance < 50% pretransplant during first week of transplantation	12 months following transplantation
Infections	Presence of a positive culture of any microorganism in presence of clinical symptoms	12 months following transplantation
Hospital admissions	Admission to the hospital for at least 24 hours	12 months following transplantation
Graft function	Creatinine clearance measured by MDRD-4	12 months following transplantation
Graft loss	Return to dialysis	12 months following transplantation
Patient survival	Patient Death	12 months following transplantation

Collaborators and Investigators

• Sponsor: Coordinación de Investigación en Salud, Mexico
• Investigators: Principal Investigator: Gustavo Martinez-Mier, MD, Jefe de División, UMAE 189, Veracruz, Veracruz

Publications and helpful links

General Publications

• Brennan DC, Daller JA, Lake KD, Cibrik D, Del Castillo D; Thymoglobulin Induction Study Group. Rabbit antithymocyte globulin versus basiliximab in renal transplantation. N Engl J Med. 2006 Nov 9;355(19):1967-77. doi: 10.1056/NEJMoa060068.
• Laftavi MR, Alnimri M, Weber-Shrikant E, Kohli R, Said M, Patel S, Pankewycz O. Low-dose rabbit antithymocyte globulin versus basiliximab induction therapy in low-risk renal transplant recipients: 8-year follow-up. Transplant Proc. 2011 Mar;43(2):458-61. doi: 10.1016/j.transproceed.2011.01.035.
• Schenker P, Ozturk A, Vonend O, Kruger B, Jazra M, Wunsch A, Kramer B, Viebahn R. Single-dose thymoglobulin induction in living-donor renal transplantation. Ann Transplant. 2011 Apr-Jun;16(2):50-8. doi: 10.12659/aot.881865.
• Gaber AO, Matas AJ, Henry ML, Brennan DC, Stevens RB, Kapur S, Ilsley JN, Kistler KD, Cosimi AB; Thymoglobulin Antibody Immunosuppression in Living Donor Recipients Investigators. Antithymocyte globulin induction in living donor renal transplant recipients: final report of the TAILOR registry. Transplantation. 2012 Aug 27;94(4):331-7. doi: 10.1097/TP.0b013e31825a7d1f.
• Hardinger KL, Schnitzler MA, Koch MJ, Labile E, Stirnemann PM, Miller B, Enkvetchakul D, Brennan DC. Thymoglobulin induction is safe and effective in live-donor renal transplantation: a single center experience. Transplantation. 2006 May 15;81(9):1285-9. doi: 10.1097/01.tp.0000209825.91632.ea.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): July 30, 2019
• Study Completion (Actual): July 30, 2019

Study Registration Dates

• First Submitted: December 27, 2016
• First Submitted That Met QC Criteria: December 27, 2016
• First Posted (Estimate): December 30, 2016

Study Record Updates

• Last Update Posted (Actual): November 15, 2019
• Last Update Submitted That Met QC Criteria: November 14, 2019
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: kidney transplantation; induction; acute rejection; basiliximab; graft loss; thymoglobulin
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Basiliximab; Thymoglobulin
• Other Study ID Numbers: R-2016-3001-61

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No IPD sharing plan