Safety Use of ATeGe in Liver Transplant Recipients With Pre-transplant Renal Dysfunction (ATG_HVH)

February 11, 2020 updated by: Cristina Dopazo Taboada, Hospital Vall d'Hebron

Single Centre, Prospective, Open, Non Controlled, Pilot Study for Efficacy and Security Evaluation of Low Nephrotoxicity Immunosuppression, Based on the Use of ATeGe in Liver Transplant Recipients With Pre-transplant Renal Dysfunction

Renal dysfunction in the context of liver transplantation is a major issue, with difficult patients' management and determining a worsened prognosis.

Physiopathologically pretransplant renal dysfunction is dependent on multifactorial causes, including hypoperfusion-derived functional renal insufficiency, hepatorenal syndrome or interstitial parenchymatous insufficiency. On top, intra- or post-transplant events, including hypoperfusion or calcineurin inhibitors nephrotoxicity may aggravate this situation.

At present MELD criteria favours allocation of organs to patients suffering from renal insufficiency, so at least 30% of the investigators liver transplant patients suffer from some degree of renal impairment pretransplant.

After liver transplant impaired renal function tends to recover partially or completely, unless advanced parenchymatous lesions are significantly involved as a major cause of renal dysfunction.

In this context, calcineurin inhibitors avoiding or sparing protocols may help in the recovery from renal insufficiency, improving long-term prognosis. The use of anti-CD25 antibodies is a good option, but provides a limited antirejection prophylaxis, limiting the use of these antibodies to a reduced cohort of liver transplant patients.

Polyclonal antibodies might provide an advantage in management of liver transplant patients with renal insufficiency, without increasing acute rejection episodes of the allograft efficacy and security evaluation of low nephrotoxicity immunosuppression, based on the use of ATeGe, in liver transplant candidates with pre-transplant renal dysfunction.

The aim of this study is to evaluate the efficacy and security use of immunosuppression based on ATeGe in liver transplant recipients with pre-transplant renal dysfunction.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 3

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

  • Spain
      • Barcelona, Spain, 08035
        • Department of HPB Surgery and Transplants, Hospital Vall d´Hebron

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

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with moderate pre-transplant renal dysfunction as defined serum creatinine levels higher than 1.5 mg/dl or eGFR (MDRD-4) <60ml/min.
  • First liver transplant, including splits liver transplant.
  • Patients aged 18-70 years
  • Without a prior contraindication for protocol biopsy of allograft.

Exclusion Criteria:

  • Multiorgan transplantation and/or liver transplant from DCD and/or with ABO incompatibility.
  • Uncontrolled concomitant infections (including HIV seropositivity) and/or diarrhoea, vomiting or active gastric ulcer.
  • Fulminant hepatic insufficiency as first indication for liver transplant
  • Hemodynamic instability prior to liver transplant.
  • Recipient presenting present or previous neoplasia, except for non-metastatic basal or squamous cutaneous carcinoma or localized hepatocarcinoma with diameter <5 cm or < 3 known lesions with diameter <3 cm.
  • Intolerance to study medication.
  • Patients having received vaccination with attenuated living vaccines within the previous 4 weeks.
  • Severe leukopenia (< 1.2 X 10E9/L) and/or thrombocytopenia (< 50x10E9/L) and/or lymphocyte counts (CD2+/CD3+) less than 10 cells/µl.
  • Significant comorbidity.
  • Breastfeeding or female patients at fertile age without negative pregnancy test and accepting the use of reliable fertility control method.

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

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Basiliximab
Historical comparable cohort treated with Basiliximab 20mg iv administered at 0 and 4th day post-transplant
Active Comparator: ATeGe-Fresenius
Drug: ATeGe-Fresenius
Administered at 1 , 3, 5 and 7 day post-transplant at 2-3mg/kg with dose adjustment according to CD2/CD3 levels

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Renal function improvement after liver transplant
Time Frame: Measurement will be performed at 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 14th and 28th day post-transplant, and 2nd, 3rd, 6th and 12th month post-transplant
Creatinine (mg/dL) and MDRD Glomerular Filtrate Rate (ml/min/1.73m2) will be measured following the time frame described above
Measurement will be performed at 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 14th and 28th day post-transplant, and 2nd, 3rd, 6th and 12th month post-transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of biopsy proven acute cellular rejection.
Time Frame: Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
If liver dysfunction is detected, percutaneous liver biopsy will be performed and histological severity will be assed following BANF criteria
Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
Patient and graft survival rates after 12 months, causes of death and retransplant
Time Frame: Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
Relationship between ATeGe doses, immunological variables (lymphocyte counts) and clinical adverse events (acute rejection,infections, HCV recurrence and de novo tumor)
Time Frame: Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
Incidence and severity of HCV infection recurrence, based on clinical and histological criteria.
Time Frame: Once liver dysfunction is detected and one year post-transplant by protocol.
Once liver dysfunction is detected and one year post-transplant by protocol.
Evaluation of metabolic complications (diabetes mellitus, arterial hypertension and dyslipidemia)
Time Frame: Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant

Collaborators and Investigators

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

Sponsor

Hospital Vall d'Hebron

Collaborators

Hospital Universitari Vall d'Hebron Research Institute

Investigators

  • Principal Investigator: ITXARONE BILBAO, PhD/MD, Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
  • Study Chair: CRISTINA DOPAZO, PhD/MD, Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
  • Study Director: RAMON CHARCO, PHD/MD, Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
  • Study Chair: MONICA MARTINEZ, PhD/MD, Department of Inmunology, Hospital Vall d´Hebron (Barcelona, Spain)
  • Study Chair: GONZALO SAPISOCHIN, PhD/MD, Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
  • Study Chair: JOSE L LAZARO, MD, Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
  • Study Chair: HELENA ALLENDE, PhD/MD, Department of Histology, Hospital Vall d´Hebron (Barcelona, Spain)

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 1, 2011

Primary Completion (Actual)

February 1, 2020

Study Completion (Actual)

February 1, 2020

Study Registration Dates

First Submitted

October 11, 2011

First Submitted That Met QC Criteria

October 13, 2011

First Posted (Estimate)

October 17, 2011

Study Record Updates

Last Update Posted (Actual)

February 12, 2020

Last Update Submitted That Met QC Criteria

February 11, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ATG-IRA-HVH.10
  • 2011-000691-34 (EudraCT Number)

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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