Efficacy of Single Dose Anti-thymocyte Globulin in the Modulation of T Lymphocytes in Kidney Transplantation

April 16, 2021 updated by: Fabiani Palagi Machado, Hospital de Clinicas de Porto Alegre

Study of the Efficacy of Single Dose Anti-thymocyte Globulin in the Modulation of T Lymphocytes in Kidney Transplant Outcomes

The use of polyclonal anti-T cell antibodies (ATG) has benefits in kidney transplantation, however, its use is associated mainly with hematological, infectious, and neoplastic complications. Monitoring T cells in patients receiving ATG was first proposed in 1975 to improve efficacy in preventing acute rejection and avoiding excessive immunosuppression. The dose regimen is guided by a daily count of TCD3+ lymphocytes. Monitoring the dose of thymoglobulin through its biological effects on T cells is a rational and safe method of titrating the dose of that antibody. This way, it is possible to reduce the total amount of drug administered to the patient and, consequently, reduce undesirable complications, as well as the cost of treatment, without losing effect on the benefit of immunosuppression.

Currently, the usual cumulative dose of ATG for induction in kidney transplant patients is 6mg/kg, in divided doses. However, the ideal dose and duration of therapy are still the subject of studies, with protocols between centers varying from total doses of 3 to 6 mg/kg, either fractionated or single, to achieve the lowest dose with fewer undesirable effects, and with reduced length of inpatient stay.

The use of ATG in a single dose of 3 mg/kg was successfully assessed for risks of infection and rejection in patients with low immunological risk.

This study proposes evaluating the efficacy and safety of a single 3mg/kg dose of ATG for patients with low and standard immune risk, with TCD3+ lymphocyte monitoring, to assess the duration of the TCD3+ cells in the peripheral blood.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Kidney transplantation is one of the major advances in medicine in the past 60 years. Currently, is considered the best treatment for terminal chronic kidney disease in the medium and long term, and the least costly. To obtain these successful outcomes, the immune response to the graft must be properly controlled and monitored since its implantation. T and B lymphocytes are crucial in the alloimmune response by mediating cellular and antibody-mediated rejections, respectively, and along with anti-HLA antibodies are the main effectors of acute and chronic rejections.

Anti-thymocyte globulin (ATG) has a key role in the immunosuppressive induction regimens used in kidney transplants as well as in the treatment of acute rejections. It is a purified solution that contains a variety of T cell-specific immunoglobulins, including CD2, CD3, CD4, CD8, CD11a, CD18, CD25, HLA-DR, and class I HLA (human leukocyte antigen). This solution is produced by immunizing rabbits with human thymocytes. The use of these agents is particularly important in inducing patients who are more predisposed to the nephrotoxic effects of calcineurin inhibitors (CI), allowing the delayed introduction of the CI. Induction with antibodies is also of great value in patients with higher immunological risk, such as pediatric, Afro-descendants, re-transplanted, and previously sensitized to HLA antigens recipients.

Polyclonal antibodies have definite benefits in kidney transplantation, but their use is associated with hematological, infectious, and neoplastic complications. The use of reduced doses of ATG has been the subject of recent studies, but still with inconclusive results.

The concept of monitoring T cells in patients receiving ATG was first proposed in 1975 to improve efficacy in preventing acute rejection and avoiding excessive immunosuppression. The dose regimen is guided by a daily count of peripheral blood TCD3+ lymphocytes. Monitoring the dose of thymoglobulin through its biological effects on T cells is a rational and safe method of titrating the dose of that antibody. This way, it is possible to reduce the total amount of drug administered to the patient and, consequently, reduce undesirable complications, as well as the cost of treatment, hopefully without losing effect on the benefit of immunosuppression.

A 60% reduction in the total dose of ATG and 58% reduction in therapy cost was observed in patients who were monitored using TCD3+ cell counts. Currently, the usual total dose of ATG for induction in kidney transplant patients is 6mg/kg, divided into 4 doses, which can be administered from day zero until day 14 (maximum) of transplantation. However, the ideal dose and duration of therapy are still the subject of investigation, with protocols between centers varying from total doses of 3 to 6 mg/kg, fractionated or single, to attempt to achieve the lowest dose with fewer undesirable effects, and with reduced length of inpatient stay. The use of ATG in a single dose of 3 mg/kg was successfully assessed for risks of infection and rejection in patients with low immunological risk.

Considering that the adverse effects associated with the use of ATG are relevant in the clinical context of kidney transplantation, the use of a lower dose, keeping its immunomodulatory effect, with a safer profile, is desirable.

The study evaluates the efficacy and safety of a single dose of 3mg/kg ATG for patients with low and standard immune risk, with TCD3+ lymphocyte monitoring, to assess the clinical efficacy and the modulation of the T cell response.

Study Type

Observational

Enrollment (Actual)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • RS
      • Porto Alegre, RS, Brazil
        • Hospital de Clínicas de Porto Alegre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

The study population will consist of patients who received a kidney transplant at a single institution between October 2018 and March 2020 and received ATG at a single dose of 3 mg/kg for induction of immunosuppression in the immediate postoperative period and a control group that received fractionated doses of 1.5 mg/kg adding up to a total of 6 mg/kg.

Description

Inclusion Criteria:

  • Kidney transplant patients from Hospital de Clínicas de Porto Alegre (HCPA) between October 2018 to March 2020 who received a single 3 mg/kg ATG dose at the immediate postoperative period. Recipients of standard and low immunological risk (PRA - panel reactive antibodies <50% and without donor-specific antibodies), regardless of the time of cold ischemia and the presence of kidney failure in the donor.
  • Control group consisting of patients from the same and previous period, who received fractionated ATG dosing up to 6 mg/kg total dose.

Exclusion Criteria:

  • Patients who used other induction strategies that did not include ATG in a single dose of 3 mg/kg or the fractionated dose of 6 mg/kg.
  • Patients who died within 24 hours after transplantation.
  • Patients who had a transplant nephrectomy within 24 hours after transplantation.
  • Pediatric recipients (< 14 years old).
  • Recipients with incomplete data.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Retrospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Multiple doses of anti-thymocyte globulin (ATG)
Control group that received fractionated doses of 1.5 mg/kg adding up to a total of 6 mg/kg
Drug: single dose of Anti-thymocyte globulin
Used anti-thymocyte globulin (ATG) in a single dose of 3 mg/kg for immunosuppression induction in the immediate postoperative period

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immunomodulatory effect
Time Frame: one year
Immunomodulatory effect of a single dose of 3mg/kg ATG on TCD3+ lymphocytes in kidney transplant patients by comparing it with the effect of the regular fractionated dose of 6 mg/kg by counting daily the number of TCD3+ lymphocytes in peripheral blood.
one year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of acute rejection
Time Frame: one year
Number of patients with acute rejection diagnosed by renal biopsy with the single-dose ATG strategy.
one year
Occurence of cytomegalovirus infection
Time Frame: One year
Number of patients with cytomegalovirus infection (positive detection through polymerase chain reaction or active disease).
One year
Incidence of delayed graft function
Time Frame: one year
Number of patients with delayed graft function (DGF) through the number of dialysis needed in the first week after kidney transplantation.
one year
One year survival of kidney grafts
Time Frame: One year
Survival of kidney grafts at 1 year after receiving a single dose of ATG.
One year
One year survival graft grafts
Time Frame: one year
Patient survival at the end of 1 year of a single dose of ATG.
one year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurence of infections and neoplasms
Time Frame: One year
Number of patients with development of other infections and neoplasms of any etiology within one year proven by clinical features and laboratory or anatomopathological tests in the study patients.
One year
Hematological effects of the drug.
Time Frame: One year
Number of patients with hematological effects (laboratory analysis of anemia, leukopenia and thrombocytopenia) of ATG.
One year
Time of inpatient stay (days).
Time Frame: One year
Length of stay in days between groups with a single and fractionated dose of atg.
One year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital de Clinicas de Porto Alegre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 20, 2018

Primary Completion (Actual)

March 31, 2020

Study Completion (Actual)

April 13, 2021

Study Registration Dates

First Submitted

March 30, 2021

First Submitted That Met QC Criteria

April 5, 2021

First Posted (Actual)

April 8, 2021

Study Record Updates

Last Update Posted (Actual)

April 19, 2021

Last Update Submitted That Met QC Criteria

April 16, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 38361620.0.0000.5327

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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