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

NCT01453218 | Completed Phase 3

• 2 other identifiers: ATG-IRA-HVH.102011-000691-34
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Insufficiency

Keywords

Renal insufficiency; Liver transplant; Acute rejection; Infections; Hepatitis C recurrence

Outcome Measures

Primary Outcomes (1)

• Renal function improvement after liver 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 Outcomes (5)

• Incidence of biopsy proven acute cellular rejection.

  Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant

• Patient and graft survival rates after 12 months, causes of death and retransplant

  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)

  Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant

• Incidence and severity of HCV infection recurrence, based on clinical and histological criteria.

  Once liver dysfunction is detected and one year post-transplant by protocol.

• Evaluation of metabolic complications (diabetes mellitus, arterial hypertension and dyslipidemia)

  Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant

Study Arms (2)

Basiliximab

NO INTERVENTION

Historical comparable cohort treated with Basiliximab 20mg iv administered at 0 and 4th day post-transplant

ATeGe-Fresenius

ACTIVE COMPARATOR

Drug: ATeGe-Fresenius

Interventions

ATeGe-Fresenius DRUG

Administered at 1 , 3, 5 and 7 day post-transplant at 2-3mg/kg with dose adjustment according to CD2/CD3 levels

ATeGe-Fresenius

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital Vall d'Hebron: lead
• Hospital Universitari Vall d'Hebron Research Institute: collaborator

Study Sites (1)

Department of HPB Surgery and Transplants, Hospital Vall d´Hebron

Barcelona, 08035, Spain

Location

Related Publications (8)

• Uemura T, Schaefer E, Hollenbeak CS, Khan A, Kadry Z. Outcome of induction immunosuppression for liver transplantation comparing anti-thymocyte globulin, daclizumab, and corticosteroid. Transpl Int. 2011 Jul;24(7):640-50. doi: 10.1111/j.1432-2277.2011.01250.x. Epub 2011 Mar 23.

  PMID: 21429047 BACKGROUND

• Benitez CE, Puig-Pey I, Lopez M, Martinez-Llordella M, Lozano JJ, Bohne F, Londono MC, Garcia-Valdecasas JC, Bruguera M, Navasa M, Rimola A, Sanchez-Fueyo A. ATG-Fresenius treatment and low-dose tacrolimus: results of a randomized controlled trial in liver transplantation. Am J Transplant. 2010 Oct;10(10):2296-304. doi: 10.1111/j.1600-6143.2010.03164.x.

  PMID: 20883560 BACKGROUND

• Soliman T, Hetz H, Burghuber C, Gyori G, Silberhumer G, Steininger R, Muhlbacher F, Berlakovich GA. Short-term induction therapy with anti-thymocyte globulin and delayed use of calcineurin inhibitors in orthotopic liver transplantation. Liver Transpl. 2007 Jul;13(7):1039-44. doi: 10.1002/lt.21185.

  PMID: 17600336 BACKGROUND

• Soliman T, Hetz H, Burghuber C, Gyori G, Silberhumer G, Steininger R, Muhlbacher F, Berlakovich GA. Short-term versus long-term induction therapy with antithymocyte globulin in orthotopic liver transplantation. Transpl Int. 2007 May;20(5):447-52. doi: 10.1111/j.1432-2277.2007.00463.x. Epub 2007 Mar 2.

  PMID: 17343686 BACKGROUND

• Kim MJ, Tsinalis D, Franz S, Binet I, Gurke L, Mihatsch MJ, Steiger J, Thiel G, Dickenmann M. ATG-Fresenius or daclizumab induction therapy in immunologically high risk kidney recipients: a prospective randomized pilot trial. Ann Transplant. 2008;13(4):21-7.

  PMID: 19034219 BACKGROUND

• Bajjoka I, Hsaiky L, Brown K, Abouljoud M. Preserving renal function in liver transplant recipients with rabbit anti-thymocyte globulin and delayed initiation of calcineurin inhibitors. Liver Transpl. 2008 Jan;14(1):66-72. doi: 10.1002/lt.21309.

  PMID: 18161842 BACKGROUND

• Tector AJ, Fridell JA, Mangus RS, Shah A, Milgrom M, Kwo P, Chalasani N, Yoo H, Rouch D, Liangpunsakul S, Herring S, Lumeng L. Promising early results with immunosuppression using rabbit anti-thymocyte globulin and steroids with delayed introduction of tacrolimus in adult liver transplant recipients. Liver Transpl. 2004 Mar;10(3):404-7. doi: 10.1002/lt.20085.

  PMID: 15004768 BACKGROUND

• Dopazo C, Charco R, Caralt M, Pando E, Lazaro JL, Gomez-Gavara C, Castells L, Bilbao I. Low Total Dose of Anti-Human T-Lymphocyte Globulin (ATG) Guarantees a Good Glomerular Filtration Rate after Liver Transplant in Recipients with Pretransplant Renal Dysfunction. Can J Gastroenterol Hepatol. 2018 Aug 16;2018:1672621. doi: 10.1155/2018/1672621. eCollection 2018.

  PMID: 30186817 DERIVED

MeSH Terms

Conditions

Renal Insufficiency; Infections

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• ITXARONE BILBAO, PhD/MD

  Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)

  PRINCIPAL INVESTIGATOR

• RAMON CHARCO, PHD/MD

  Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)

  STUDY DIRECTOR

• 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)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant and Liver Surgeon

Study Record Dates

• First Submitted: October 11, 2011
• First Posted: October 17, 2011
• Study Start: October 1, 2011
• Primary Completion: February 1, 2020
• Study Completion: February 1, 2020
• Last Updated: February 12, 2020

Record last verified: 2020-02

Locations

ES (1)