- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT01453218
Safety Use of ATeGe in Liver Transplant Recipients With Pre-transplant Renal Dysfunction (ATG_HVH)
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.
Studieöversikt
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 3
Kontakter och platser
Studieorter
-
-
-
Barcelona, Spanien, 08035
- Department of HPB Surgery and Transplants, Hospital Vall d´Hebron
-
-
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
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.
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Grundläggande vetenskap
- Tilldelning: Icke-randomiserad
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
---|---|
Inget ingripande: Basiliximab
Historical comparable cohort treated with Basiliximab 20mg iv administered at 0 and 4th day post-transplant
|
|
Aktiv komparator: ATeGe-Fresenius
|
Administered at 1 , 3, 5 and 7 day post-transplant at 2-3mg/kg with dose adjustment according to CD2/CD3 levels
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Renal function improvement after liver transplant
Tidsram: 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
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Incidence of biopsy proven acute cellular rejection.
Tidsram: 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
Tidsram: 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)
Tidsram: 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.
Tidsram: 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)
Tidsram: Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
|
Evaluation at 1st , 3rd, 6th, 9th and 12th month post-transplant
|
Samarbetspartners och utredare
Sponsor
Samarbetspartners
Utredare
- Huvudutredare: ITXARONE BILBAO, PhD/MD, Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
- Studiestol: CRISTINA DOPAZO, PhD/MD, Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
- Studierektor: RAMON CHARCO, PHD/MD, Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
- Studiestol: MONICA MARTINEZ, PhD/MD, Department of Inmunology, Hospital Vall d´Hebron (Barcelona, Spain)
- Studiestol: GONZALO SAPISOCHIN, PhD/MD, Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
- Studiestol: JOSE L LAZARO, MD, Department of HPB Surgery and Transplants, Hospital Vall d´Hebron (Barcelona, Spain)
- Studiestol: HELENA ALLENDE, PhD/MD, Department of Histology, Hospital Vall d´Hebron (Barcelona, Spain)
Publikationer och användbara länkar
Allmänna publikationer
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- ATG-IRA-HVH.10
- 2011-000691-34 (EudraCT-nummer)
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .
Kliniska prövningar på Njurinsufficiens
-
Universitaire Ziekenhuizen KU LeuvenAvslutadPrevalens av Augmented Renal Clearance | Riskfaktorer för ökad renal clearanceBelgien
-
The First People's Hospital of ChangzhouHar inte rekryterat ännu
-
Andrew B AdamsBristol-Myers SquibbAvslutadMisslyckad renal allograftFörenta staterna
-
Oregon Health and Science UniversityAvslutad
-
Assiut UniversityOkänd
-
The Methodist Hospital Research InstituteOkändAkut (cellulär) renal allograftavstötningFörenta staterna
-
Fady M Kaldas, M.D., F.A.C.S.RekryteringBedömer immunsuppressionsmodulering på renal återhämtning efter LTFörenta staterna
-
Erling Bjerregaard PedersenUniversity of AarhusOkändRenal Tubular TransportDanmark
Kliniska prövningar på ATeGe-Fresenius
-
Medical University of ViennaAvslutad
-
University Health Network, TorontoHeart and Stroke Foundation of OntarioAvslutadHjärtsjukdom | Neurokognitiv nedgångKanada
-
Astellas Pharma China, Inc.AvslutadMottagare av njurtransplantationKina
-
Kyungpook National University HospitalMinistry of Health & Welfare, Korea; Fresenius Medical Care KoreaAvslutadNjursvikt, kronisk | Störningar associerade med peritonealdialysKorea, Republiken av
-
Lawson Health Research InstituteWestern University, CanadaAvslutadHjärtkirurgiska ingrepp
-
Ullevaal University HospitalRikshospitalet University HospitalAvslutadExtrakorporeal koagulering under hemodialysNorge
-
UConn HealthDialysis Clinic, Inc.; Nipro Medical CorporationAvslutad
-
YUAN Wei-jieOkänd
-
IRCCS Policlinico S. MatteoItalian Association for Pediatric Hematology OncologyOkändPediatriska patienter drabbade av hematologiska maligniteter och berättigade att genomgå HSCT från en icke-närstående volontärItalien