Clinical trial NCT01453218: Safety Use of ATeGe in Liver Transplant Recipients With Pre-transplant Renal Dysfunction
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Renal Insufficiency
Keywords: Renal insufficiency
Liver transplant
Acute rejection
Infections
Hepatitis C recurrence
Lead sponsor: Hospital Vall d'Hebron
Sponsor class: OTHER
Collaborators: name: Hospital Universitari Vall d'Hebron Research Institute
First posted: 2011-10-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Renal function improvement after liver transplant
timeFrame: 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 outcomes:
measure: Incidence of biopsy proven acute cellular rejection.
timeFrame: Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
measure: Patient and graft survival rates after 12 months, causes of death and retransplant
timeFrame: Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
measure: Relationship between ATeGe doses, immunological variables (lymphocyte counts) and clinical adverse events (acute rejection,infections, HCV recurrence and de novo tumor)
timeFrame: Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
measure: Incidence and severity of HCV infection recurrence, based on clinical and histological criteria.
timeFrame: Once liver dysfunction is detected and one year post-transplant by protocol.
measure: Evaluation of metabolic complications (diabetes mellitus, arterial hypertension and dyslipidemia)
timeFrame: Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Department of HPB Surgery and Transplants, Hospital Vall d´Hebron
Study officials:
affiliation: Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
name: ITXARONE BILBAO, PhD/MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
name: RAMON CHARCO, PHD/MD
role: STUDY_DIRECTOR
affiliation: Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
name: CRISTINA DOPAZO, PhD/MD
role: STUDY_CHAIR
affiliation: Department of Inmunology, Hospital Vall d´Hebron (Barcelona, Spain)
name: MONICA MARTINEZ, PhD/MD
role: STUDY_CHAIR
affiliation: Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
name: GONZALO SAPISOCHIN, PhD/MD
role: STUDY_CHAIR
affiliation: Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
name: JOSE L LAZARO, MD
role: STUDY_CHAIR
affiliation: Department of Histology, Hospital Vall d´Hebron (Barcelona, Spain)
name: HELENA ALLENDE, PhD/MD
role: STUDY_CHAIR
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