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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Hospital Vall d'Hebron
Sponsor:
Collaborator:
Hospital Universitari Vall d'Hebron Research Institute
Information provided by (Responsible Party):
Cristina Dopazo Taboada, Hospital Vall d'Hebron
ClinicalTrials.gov Identifier:
NCT01453218
First received: October 11, 2011
Last updated: August 14, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Renal Insufficiency
Drug: ATeGe-Fresenius
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Hospital Vall d'Hebron:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    Creatinine (mg/dL) and MDRD Glomerular Filtrate Rate (ml/min/1.73m2) will be measured following the time frame described above


Secondary Outcome Measures:
  • Incidence of biopsy proven acute cellular rejection. [ Time Frame: Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant ] [ Designated as safety issue: Yes ]
    If liver dysfunction is detected, percutaneous liver biopsy will be performed and histological severity will be assed following BANF criteria

  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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. ] [ Designated as safety issue: Yes ]
  • Evaluation of metabolic complications (diabetes mellitus, arterial hypertension and dyslipidemia) [ Time Frame: Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: October 2011
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01453218

Contacts
Contact: Cristina Dopazo, PhD/MD +3493274600 ext 6113 cdopazo@vhebron.net

Locations
Spain
Department of HPB Surgery and Transplants, Hospital Vall d´Hebron Recruiting
Barcelona, Spain, 08035
Contact: Cristina Dopazo, PhD/MD    +34932746000 ext 6113    cdopazo@vhebron.net   
Sponsors and Collaborators
Hospital Vall d'Hebron
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 Director: RAMON CHARCO, 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 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)
  More Information

Publications:

Responsible Party: Cristina Dopazo Taboada, Consultant and Liver Surgeon, Hospital Vall d'Hebron
ClinicalTrials.gov Identifier: NCT01453218     History of Changes
Other Study ID Numbers: ATG-IRA-HVH.10, 2011-000691-34
Study First Received: October 11, 2011
Last Updated: August 14, 2014
Health Authority: Spain: Comité Ético de Investigación Clínica
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Ministry of Health

Keywords provided by Hospital Vall d'Hebron:
Renal insufficiency
Liver transplant
Acute rejection
Infections
Hepatitis C recurrence

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on September 18, 2014