De Novo Renal Transplant Recipient. Clinical Trial
Official title:
An Open, Prospective, Randomised, Controlled, Multi-Center Study Comparing Fixed Dose vs Concentration Controlled Mycophenolate Mofetil Regimens for de Novo Patients Following Transplantation
Determine the value of a clinically feasible strategy of therapeutic drug monitoring compared with fixed dosing in de novo MMF treated renal transplant recipients with respect to the incidence of treatment failure.
| Status | Completed |
| Enrollment | 901 |
| Est. completion date | April 2006 |
| Est. primary completion date | March 2005 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 2 Years and older |
| Eligibility |
Inclusion Criteria: - Renal transplant recipients who have completed their second birthday, - Recipients from living (related or unrelated), cadaveric (non-heart beating or heart beating) donors, - Single organ recipient (kidney only), - Women of childbearing potential should have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/ml within 1 week prior to beginning MMF treatment. Effective contraception must be used before beginning therapy, during therapy and for 6 weeks following discontinuation of therapy, even where there has been a history of infertility, unless due to hysterectomy, - Patients or patient's parent/guardian providing written informed consent, - Patients co-operative and able to complete all the assessment procedures. Exclusion Criteria: - Patients receiving immunosuppressive therapy (except steroid treatment) within the preceding 28 days, except that immunosuppressive medication may be initiated up to 48 hours before transplantation. Furthermore, all patients should receive 1 g [adults] or 600 mg/m2 [paediatric patients] of MMF therapy within 6 hours prior to transplantation, - PRA > 50% within 6 months prior to enrolment, - Cold ischaemia time >48 hours, - History of malignancy (except localised non-melanotic skin cancer) or the presence of any active malignancy at the time of transplant, - Active peptic ulcer disease, - Active infection, - Mandatory intake of prohibited drugs or it is probable that the patient will require treatment with such drugs after transplant, - Pregnant or lactating females, - Women of child-bearing potential not willing to use a reliable form of contraception, - Patient is allergic or intolerant to polysorbate 80 (TWEEN), phenylalanine (aspartame), steroids, MMF, MPA, tacrolimus or cyclosporin, - Patient or donor with positive tests for HIV or hepatitis B surface antigen, - Patients with liver cirrhosis or clinical evidence of portal hypertension or other indication of moderate or severe liver disease. (Note: it is strongly recommended that patients with hepatitis C have a liver biopsy performed prior to transplantation), - Incompatible ABO blood type and/or positive crossmatch, - Patient has any form of substance abuse, psychiatric disorder or condition, which, in the opinion of the investigator, may invalidate communication with the investigator or with study procedures, - Patients whose laboratory results reveal severe anaemia (as defined by a haemoglobin value <6 mmol/L [9.7 g/dL] for adults receiving erythropoietin, <4.1 mmol/L [6.6 g/dL] for paediatric patients [regardless of erythropoietin treatment]), leukopenia (as defined by a WBC value of <2500/mm3) or thrombocytopenia (as defined by a platelet count of <75,000/mm3). |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Australia | Princess Alexandra Hospital | Brisbane | Queensland |
| Australia | Monash Medical Centre | Clayton | Victoria |
| Australia | St Vincent's Hospital | Melbourne | Victoria |
| Australia | Sir Charles Gairdner Hospital | Nedlands | Western Australia |
| Australia | John Hunter Hospital | New Lambton | New South Wales |
| Australia | Royal Melbourne Hospital | Parkville | Victoria |
| Australia | Royal Perth Hospital | Perth | Western Australia |
| Austria | Med. Univ. Klinik | Graz | |
| Austria | AKH Wien | Vienna | |
| Belgium | University Hospitals Leuven | Leuven | |
| Brazil | Hospital do Rim e Hipertensao | Sao Paulo | |
| Canada | Vancouver General Hospital | Vancouver | British Columbia |
| China | West China Hospital of Sichuan University | Chengdu | Sichuan |
| China | Ruijin Hospital | Shanghai | Shanghai |
| Denmark | Odense University Hospital | Odense | |
| Estonia | Surgical Clinic Of Tartu University Clinics | Tartu | |
| France | Hopital Pellegrin, C.H.R.de Bordeaux | Bordeaux | |
| France | Hospital du Bocage | Dijon | |
| France | CHU de Grenoble | Grenoble | |
| France | CHU Kremlin Bicêtre | Kremlin Bicêtre | |
| France | Hopital Calmette | Lille | |
| France | Hopital Jeanne de Flandres | Lille | |
| France | Centre Hospitalier Regional Universitaire | Limoges | |
| France | CHU Hotel Dieu | Nantes | |
| France | Hopital Necker | Paris | |
| France | Hopital Tenon | Paris | |
| France | Centre Hospitalier Lyon Sud | Pierre Benite | |
| France | Hopital Foch | Suresnes | |
| France | CHU Purpan | Toulouse | |
| France | CHU Rangueil | Toulouse | |
| France | CHU de Nancy-Brabois | Vandoeuvre-les-Nancy | |
| Germany | Universitatsklinikum Charite | Berlin | |
| Germany | Chirurgische Universitätsklinik | Freiburg | |
| Germany | Universitatsklinikum Heidelberg | Heidelberg | |
| Germany | University of Heidelberg | Heidelberg | |
| Germany | Stadt Kliniken Koln | Koln | |
| Germany | University Hospital Wurzburg | Wurzburg | |
| Lithuania | Vilnius University Hospital | Vilnius | |
| Netherlands | Leids Universitair Medisch Centrum | Leiden | |
| Netherlands | Erasmus Medical Center Rotterdam | Rotterdam | |
| Norway | Rikshopitalet | Oslo | |
| Poland | Children's Memorial Health Institute | Warsaw | |
| Poland | Institute of Transplantology, Medical University of Warsaw | Warsaw | |
| Spain | Hospital Infanta Christa | Badajoz | |
| Spain | Hospital Del Mar | Barcelona | |
| Spain | Hospital Sant Joan de Deu | Barcelona | |
| Spain | Valle de Hebron | Barcelona | |
| Spain | Hospital Reina Sofia | Cordoba | |
| Spain | Hospital de las Nieves | Granada | |
| Spain | Fundacion Jimenez Diaz | Madrid | |
| Spain | Hospital Clinico San Carlos | Madrid | |
| Spain | Hospital Ramon Y Cajal | Madrid | |
| Spain | La Paz | Madrid | |
| Spain | Hospital Son Dureta | Palma De Mallorca | 07014 |
| Spain | Complejo Hospitalario Univeritario de Santiago | Santiago De Compostela | |
| Spain | Hospital Virgen del Rocio | Sevilla | |
| Spain | Hospital Dr. Peset | Valencia | |
| Sweden | University Hospital, Malmo | Malmo | |
| Sweden | Karolinska University Hospital, Huddinge | Stockholm | |
| Sweden | University Hospital A | Uppsala | |
| Taiwan | National Taiwan University Hospital | Taipei | |
| United Kingdom | Guys and St Thomas's Hospital | London | |
| United Kingdom | Royal Free Hospital | London | |
| United Kingdom | St George's Hospital | London | |
| Venezuela | Hospital "Miguel Perez Carreno" | Caracas | |
| Venezuela | Hospital Universitario de Caracas | Caracas | |
| Venezuela | Hospital Universitario de Maracaibo | Maracaibo |
| Lead Sponsor | Collaborator |
|---|---|
| Erasmus Medical Center | Hoffmann-La Roche |
Australia, Austria, Belgium, Brazil, Canada, China, Denmark, Estonia, France, Germany, Lithuania, Netherlands, Norway, Poland, Spain, Sweden, Taiwan, United Kingdom, Venezuela,
van Gelder T, Hilbrands LB, Vanrenterghem Y, Weimar W, de Fijter JW, Squifflet JP, Hené RJ, Verpooten GA, Navarro MT, Hale MD, Nicholls AJ. A randomized double-blind, multicenter plasma concentration controlled study of the safety and efficacy of oral mycophenolate mofetil for the prevention of acute rejection after kidney transplantation. Transplantation. 1999 Jul 27;68(2):261-6. — View Citation
van Gelder T, Silva HT, de Fijter JW, Budde K, Kuypers D, Tyden G, Lohmus A, Sommerer C, Hartmann A, Le Meur Y, Oellerich M, Holt DW, Tönshoff B, Keown P, Campbell S, Mamelok RD. Comparing mycophenolate mofetil regimens for de novo renal transplant recipi — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Treatment failure including the occurrence of the first one of any of the following: biopsy-proven acute rejection, graft loss, death or discontinuation of MMF therapy during the first 12 months following transplantation. | 12 Months | No | |
| Secondary | Proportion of patients treated for acute rejection during the first 3, 6, 12 months post-transplantation, | 3, 6 and 12 Months | No | |
| Secondary | Time to first acute rejection, | 12 Months | No | |
| Secondary | Number of acute rejection episodes per patient in the first year post-transplantation, | 12 Months | No | |
| Secondary | Overall treatment outcome at 12 months post-transplantation which is composed of any one of the following: | 12 Months | No | |
| Secondary | Graft loss, | 12 Months | No | |
| Secondary | Death, | 12 Months | No | |
| Secondary | Discontinuation of MMF therapy, | 12 Months | No | |
| Secondary | Patient lost to follow-up. | 12 Months | No |