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Study Comparing Effect On Carotid Atherosclerosis Following Conversion From Tacrolimus To Sirolimus Post-Transplant In Kidney Transplant Patients

19 juillet 2013 mis à jour par: Pfizer

A Prospective, Randomized, Open-Label, Pilot Study To Compare The Effect On Carotid Atherosclerosis Of A Tacrolimus-Based Regimen With Conversion From A Tacrolimus- To A Sirolimus-Based Regimen At 3-4 Months Post-Transplant In De Novo Renal Transplant Recipients

The purpose of this study is to determine whether immunosuppression by tacrolimus, mycophenolate mofetil, and prednisone compared to conversion to sirolimus, mycophenolate mofetil, and prednisone affect the progression of atherosclerosis in renal transplant recipients.

Aperçu de l'étude

Statut

Résilié

Les conditions

Intervention / Traitement

Description détaillée

A decision to terminate the study was taken in November 2011 and a communication to that effect sent to all participating sites on November 18. All sites were asked to have patients returned to the sites and have all end of study procedures performed by Dec 31, 2011.

The decision to terminate this study was made following the conduct of an interim analysis which demonstrated that the study did not reach its primary endpoint. The termination of this study was not driven by any safety concerns and had no impact on subject safety and well-being.

Type d'étude

Interventionnel

Inscription (Réel)

72

Phase

  • Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 2T9
        • Pfizer Investigational Site
      • Edmonton, Alberta, Canada, T6G 2B7
        • Pfizer Investigational Site
    • Ontario
      • Hamilton, Ontario, Canada, L8N 4A6
        • Pfizer Investigational Site
      • London, Ontario, Canada, N6A 5A5
        • Pfizer Investigational Site
      • Toronto, Ontario, Canada, M5C 2T2
        • Pfizer Investigational Site
      • Toronto, Ontario, Canada, M5B 1W8
        • Pfizer Investigational Site
    • Quebec
      • Montreal, Quebec, Canada, H1T 2M4
        • Pfizer Investigational Site
  • États-Unis
    • New York
      • Rochester, New York, États-Unis, 14642
        • Pfizer Investigational Site

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

35 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

At least one of the following characteristics:

  • History of dialysis for at least 3 years.
  • History of diabetes for at least 5 years.
  • Hypertension or ischemic nephropathy as a cause of the end stage renal disease or loss of the first transplant.
  • History of coronary artery disease, stroke, myocardial infarction, or amputation for vascular disease.

Exclusion Criteria:

  • History of malignancy within the last 5 years (except adequately treated skin cancer).
  • Recipients of non-renal organ transplant.
  • Active gastrointestinal disease that may interfere with drug absorption.
  • Active HIV, hepatitis B or C infection.
  • Women who are pregnant or breastfeeding.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Comparateur actif: 1
Tacrolimus + MMF + Steroids
Médicament: tacrolimus
The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol TAC should be initiated within 24 hours before or after transplantation or within 14 days of transplantation as per local standard of care and tapered to a target trough level of 3-10 ng/mL by the Pre-Conversion visit at month 3-4 post-transplantation. The target trough level of TAC will be maintained at 3-10 ng/mL through to the end of the study.
Autres noms:
  • CNI
Médicament: mycophenolate mofetil
The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol MMF or MPS should be initiated within 24 hours before or after transplantation or within 14 days of transplantation per local standard of care and tapered to a minimum oral dose of MMF ≥ 500 mg/day or MPS ≥ 360 mg/day by the Pre-Conversion visit at month 3-4 post-transplantation. At the discretion of the investigator, MMF may be changed to MPS, or MPS may be changed to MMF. MMF is to be continued at ≥ 500 mg/day dose or MPS is to be continued at ≥ 360 mg/day dose through to the end of study.
Autres noms:
  • MMF, MPS
Médicament: prednisone
The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol CCS should be initiated within 24 hours before or after transplantation or within 14 days of transplantation per local standard of care and tapered to a minimum of 5 mg/day of prednisone orally or the alternate day equivalent by the Pre-Conversion visit at month 3-4 post-transplant. Continue administration of prednisone as per local standard of care to a minimum dose of 2.5 mg/day or alternate day equivalent dose to the end of the study. Withdrawal of CCS is prohibited.
Autres noms:
  • CSC
Médicament: tacrolimus
The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol TAC should be initiated within 24 hours before or after transplantation or within 14 days of transplantation as per local standard of care and tapered to a target trough level of 3-10 ng/mL by the Pre-Conversion visit at month 3-4 post-transplantation. Reintroduction of TAC or introduction of CsA is not permitted in the SRL Therapy group.
Autres noms:
  • CNI
Expérimental: 2
Tacrolimus + MMF + Steroids with conversion from Tacrolimus to Sirolimus at 3-4 months post-transplant
Médicament: tacrolimus
The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol TAC should be initiated within 24 hours before or after transplantation or within 14 days of transplantation as per local standard of care and tapered to a target trough level of 3-10 ng/mL by the Pre-Conversion visit at month 3-4 post-transplantation. The target trough level of TAC will be maintained at 3-10 ng/mL through to the end of the study.
Autres noms:
  • CNI
Médicament: mycophenolate mofetil
The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol MMF or MPS should be initiated within 24 hours before or after transplantation or within 14 days of transplantation per local standard of care and tapered to a minimum oral dose of MMF ≥ 500 mg/day or MPS ≥ 360 mg/day by the Pre-Conversion visit at month 3-4 post-transplantation. At the discretion of the investigator, MMF may be changed to MPS, or MPS may be changed to MMF. MMF is to be continued at ≥ 500 mg/day dose or MPS is to be continued at ≥ 360 mg/day dose through to the end of study.
Autres noms:
  • MMF, MPS
Médicament: prednisone
The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol CCS should be initiated within 24 hours before or after transplantation or within 14 days of transplantation per local standard of care and tapered to a minimum of 5 mg/day of prednisone orally or the alternate day equivalent by the Pre-Conversion visit at month 3-4 post-transplant. Continue administration of prednisone as per local standard of care to a minimum dose of 2.5 mg/day or alternate day equivalent dose to the end of the study. Withdrawal of CCS is prohibited.
Autres noms:
  • CSC
Médicament: tacrolimus
The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol TAC should be initiated within 24 hours before or after transplantation or within 14 days of transplantation as per local standard of care and tapered to a target trough level of 3-10 ng/mL by the Pre-Conversion visit at month 3-4 post-transplantation. Reintroduction of TAC or introduction of CsA is not permitted in the SRL Therapy group.
Autres noms:
  • CNI
Médicament: sirolimus

The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol.

On study Day 1 Conversion, the daily dose of TAC will not be taken, and SRL is initiated as a single 5-10 mg loading dose, followed by 3 mg/day on subsequent days, adjusted to maintain a SRL target trough level of 8-15 ng/mL through to month 24 post-transplant, then 5-12 ng/mL to the end of month 36 post-transplant.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Annual Change Rate in Total Plaque Volume (TPV) From Pre-conversion Baseline to 12 Months Post-transplant
Délai: Pre-conversion baseline and 12 months post-transplant
Within-subject annual change rate in TPV in the left and right distal common carotid arteries from the pre-conversion baseline to 12 months post kidney transplant as determined by ultrasound. Annual change rate equals (=) (TPV at month 12 post-transplant minus [-] TPV at pre-conversion baseline) divided (/) by imaging interval in years. TPV is the sum of assessment in left and right distal common carotid arteries.
Pre-conversion baseline and 12 months post-transplant
TPV at Pre-conversion Baseline
Délai: Pre-conversion baseline
TPV is the sum of the assessment in left and right distal common carotid arteries.
Pre-conversion baseline

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Annual Change Rate in Carotid Intima Media Thickness (CIMT) From Pre-conversion Baseline at 12, 18, 24 and 36 Months Post-transplant
Délai: Pre-conversion baseline, and 12, 18, 24 and 36 months post-transplant
Within-subject annual change rate in CIMT as determined by ultrasound. Mean CIMT=average of left CIMT and right CIMT. Annual CIMT Change Rate (mm/year) = (CIMT at Month x Post-transplant Visit - CIMT at Conversion Baseline) / Imaging interval in years.
Pre-conversion baseline, and 12, 18, 24 and 36 months post-transplant
CIMT at Pre-conversion Baseline
Délai: Pre-conversion baseline
Mean CIMT=average of left CIMT and right CIMT.
Pre-conversion baseline
Change From Pre-conversion Baseline in Carotid Plaque Roughness at 12 and 24 Months Post-transplant
Délai: Pre-conversion baseline, 12, and 24 months post-transplant
Carotid plaque roughness as determined by ultrasound. Change equals (=) value at post-transplant month x minus (-) pre-conversion baseline.
Pre-conversion baseline, 12, and 24 months post-transplant
Change From Pre-conversion Baseline in Fasting Lipid Parameters at 12, 18, 24 and 36 Months Post-transplant
Délai: Pre-conversion baseline, and 12, 18, 24 and 36 months post-transplant
Total Cholesterol (TC), Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL) and Triglyceride (Tg) blood concentrations. Higher levels of TC, LDL and Tg are less desirable. Lower levels of HDL are less desirable. Change for each parameter = value at 12, 18, 24 and 36 months post-transplant - value at pre-conversion baseline.
Pre-conversion baseline, and 12, 18, 24 and 36 months post-transplant
Change From Pre-conversion Baseline in Glucose at Months 12, 24 and 36 Post-transplant
Délai: Pre-conversion baseline, 12, 24 and 36 months post-transplant
Fasting plasma glucose. Change = value at month x post-transplant - pre-conversion baseline values.
Pre-conversion baseline, 12, 24 and 36 months post-transplant
Change From Pre-conversion Baseline in Insulin at Months 12, 24, and 36 Post-transplant
Délai: Pre-conversion baseline, 12, 24 and 36 months post-transplant
Fasting insulin. Change = value at month x post-transplant - pre-conversion baseline.
Pre-conversion baseline, 12, 24 and 36 months post-transplant
Change From Pre-conversion Baseline in Glycosylated Hemoglobin(HbA1C) at Months 12, 24, and 36 Post-transplant
Délai: Pre-conversion baseline, 12, 24 and 36 months post-transplant
HbA1C, change = value at month x post-transplant - pre-conversion baseline.
Pre-conversion baseline, 12, 24 and 36 months post-transplant
Change From Pre-conversion Baseline in Adiponectin at Months 12, 24 and 36 Post-transplant
Délai: Pre-conversion baseline, 12, 24 and 36 months post-transplant
Adiponectin is a biomarker for cardiovascular disease and atherosclerosis risk. A higher level indicates less risk. Change = month x post-transplant values - pre-conversion baseline values.
Pre-conversion baseline, 12, 24 and 36 months post-transplant
Change From Pre-conversion Baseline in High Sensitivity C-Reactive Protein (hsCRP) at Months 12, 24 and 36 Post-transplant.
Délai: Pre-conversion baseline, 12, 24 and 36 months post-transplant
hsCRP is a biomarker of cardiovascular disease and atherosclerosis risk. A higher level indicates a greater risk. Change = month x post-transplant values - pre-conversion baseline values.
Pre-conversion baseline, 12, 24 and 36 months post-transplant
Change From Pre-conversion Baseline in Tumor Necrosis Factor Alpha (TNF-alpha) at Months 12, 24 and 36 Post-transplant
Délai: Pre-conversion baseline, 12, 24 and 36 months post-transplant
TNF-alpha is a biomarker for cardiovascular disease and atherosclerosis risk. A higher level indicates a greater risk. Change = month x post-transplant values - pre-conversion baseline values.
Pre-conversion baseline, 12, 24 and 36 months post-transplant
Change From Pre-conversion Baseline in Endothelin-1 at Months 12, 24 and 36 Post-transplant
Délai: Pre-conversion baseline, 12, 24 and 36 months post-transplant
Endothelin-1 is a biomarker for cardiovascular disease and atherosclerosis risk. A higher level indicates greater risk. Change = month x post-transplant values - pre-conversion baseline values.
Pre-conversion baseline, 12, 24 and 36 months post-transplant
Change From Pre-conversion Baseline in Interleukin-6 (IL-6) at Months 12, 24 and 36 Post-transplant
Délai: Pre-conversion baseline, 12, 24 and 36 months post-transplant
IL-6 is a biomarker for cardiovascular disease and atherosclerosis risk. A higher level indicates a greater risk. Change = month x post-transplant values - pre-conversion values.
Pre-conversion baseline, 12, 24 and 36 months post-transplant
Change From Pre-conversion Baseline in Homocysteine at Months 12, 24 and 36 Post-transplant
Délai: Pre-conversion baseline, 12, 24 and 36 months post-transplant
Homocysteine is a biomarker for cardiovascular disease and atherosclerosis risk. A higher level indicates a greater risk. Change = month x post-transplant values - pre-conversion baseline values.
Pre-conversion baseline, 12, 24 and 36 months post-transplant
Change From Pre-conversion Baseline in Lipoprotein(a) at Months 12, 24 and 36 Post-transplant
Délai: Pre-conversion baseline, 12, 24 and 36 months post-transplant
Lipoprotein(a) is a biomarker for cardiovascular disease and atherosclerosis risk. A higher level indicates a greater risk. Change = month x post-transplant values - pre-conversion baseline values.
Pre-conversion baseline, 12, 24 and 36 months post-transplant
Change From Pre-conversion Baseline in Fibrinogen at Months 12, 24 and 36 Post-transplant
Délai: Pre-conversion baseline, 12, 24 and 36 months post-transplant
Fibrinogen is a biomarker for cardiovascular disease and atherosclerosis risk. A higher level indicates a greater risk. Change = month x post-transplant values - pre-conversion baseline values.
Pre-conversion baseline, 12, 24 and 36 months post-transplant
Change From Pre-conversion Baseline in Vitamin B12 at Months 12, 24 and 36 Post-transplant
Délai: Pre-conversion baseline, 12, 24 and 36 months post-transplant
Vitamin B12 is a biomarker for cardiovascular disease and atherosclerosis risk. A lower level indicates a greater risk. Change = month x post-transplant values - pre-conversion values.
Pre-conversion baseline, 12, 24 and 36 months post-transplant
Change From Pre-conversion Baseline in Uric Acid at Months 12, 24 and 36 Post-transplant
Délai: Pre-conversion baseline, 12, 24 and 36 months post-transplant
Uric Acid is a biomarker for cardiovascular disease and atherosclerosis risk. A higher level indicates a greater risk. Change = month x post-transplant values - pre-conversion baseline values.
Pre-conversion baseline, 12, 24 and 36 months post-transplant
Change From Pre-conversion Baseline in Folate at 12, 24 and 36 Months Post-transplant
Délai: Pre-conversion baseline, 12, 24 and 36 months post-transplant
Folate is a biomarker for cardiovascular disease and atherosclerosis risk. A lower level indicates a greater risk. Change = month x post-transplant values - pre-conversion baseline values.
Pre-conversion baseline, 12, 24 and 36 months post-transplant
Number of Participants Who Used Lipid Lowering Therapies
Délai: From consent to conversion, from conversion to Month 12, from Months 12 to 24, and from Months 24 to 36 post-transplant
Participants who reported "yes" for taking lipid lowering therapies as concomitant medication.
From consent to conversion, from conversion to Month 12, from Months 12 to 24, and from Months 24 to 36 post-transplant
Number of Participants Who Used Anti-hypertensive Medications
Délai: From consent to conversion, from conversion to Month 12, from Months 12 to 24, and from Months 24 to 36 post-transplant
Participants who reported "yes" for taking anti-hypertensive medications as concomitant medication.
From consent to conversion, from conversion to Month 12, from Months 12 to 24, and from Months 24 to 36 post-transplant
Annual Rate of Change in TPV From Pre-conversion Baseline to 18, 24 and 36 Months Post Transplant
Délai: Pre-conversion baseline, and 18, 24 and 36 months post-transplant
Within-subject annual change rate in TPV in the left and right distal common carotid arteries from the pre-conversion baseline to 18, 24 and 36 months post kidney transplant as determined by ultrasound. Annual change rate equals (=) (TPV at month 18, 24 and 36 post-transplant minus [-] TPV at pre-conversion baseline) divided (/) by imaging interval in years. TPV is the sum of assessment in left and right distal common carotid arteries.
Pre-conversion baseline, and 18, 24 and 36 months post-transplant

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Pfizer

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Liens utiles

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 avril 2006

Achèvement primaire (Réel)

1 décembre 2010

Achèvement de l'étude (Réel)

1 janvier 2012

Dates d'inscription aux études

Première soumission

3 avril 2006

Première soumission répondant aux critères de contrôle qualité

3 avril 2006

Première publication (Estimation)

5 avril 2006

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

23 septembre 2013

Dernière mise à jour soumise répondant aux critères de contrôle qualité

19 juillet 2013

Dernière vérification

1 juillet 2013

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 0468H1-319

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