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12 Month Athena Study: Everolimus vs. Standard Regimen in de Novo Kidney Transplant Patients (ATHENA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01843348
Recruitment Status : Completed
First Posted : April 30, 2013
Results First Posted : May 1, 2017
Last Update Posted : May 1, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This study was designed to evaluate the renal function comparing Certican based immunosuppressive regimens with two different CNIs (Tacrolimus or Cyclosporin A) versus a standard treatment with Mycophenolic Acid and Tacrolimus in de novo renal transplant recipients.

Condition or disease Intervention/treatment Phase
Kidney Transplantation Renal Transplantation Drug: Everolimus Drug: Tacrolimus Drug: Cyclosporin A Drug: Enteric Coated Mycophenolate Sodium (EC-MPS) Drug: Mycophenolate mofetil (MMF) Drug: Corticosteroids Drug: Simulect Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 612 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 12 Month, Multi-center, Open-label, Prospective, Randomized, Parallel Group Study Investigating a Standard Regimen in de Novo Kidney Transplant Patients Versus a Certican® Based Regimen Either in Combination With Cyclosporin A or Tacrolimus
Actual Study Start Date : December 27, 2012
Actual Primary Completion Date : March 23, 2016
Actual Study Completion Date : March 23, 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Everolimus

Arm Intervention/treatment
Active Comparator: TAC+MPA Drug: Tacrolimus
Capsules: 0.5 mg, 1 mg or 5 mg. Dosing schedule: transplant to month 2: 4-8ng/ml, month 3 to month 12 3-5 ng/ml according to standard blood levels

Drug: Enteric Coated Mycophenolate Sodium (EC-MPS)
Tablets: 180 mg or 360 mg. Dosing: duration of study 360 mg bid and no less than 360 mg daily dose

Drug: Mycophenolate mofetil (MMF)
Capsules: 250 or 500 mg. Dosing: duration of study 500 mg bid and no less than 500 mg total daily dose

Drug: Corticosteroids
A minimum dose of 5 mg prednisolon or equivalent

Drug: Simulect
Lyophilisate in vials with ampoules of sterile water for injection (5 mL), one vial containing 20 mg lyophilisate given intravenously on the day of transplantation and on day four post-transplantation.
Other Name: Basiliximab

Experimental: TAC+Certican Drug: Everolimus
Other Name: Certican

Drug: Tacrolimus
Capsules: 0.5 mg, 1 mg or 5 mg. Dosing schedule: transplant to month 2: 4-8ng/ml, month 3 to month 12 3-5 ng/ml according to standard blood levels

Drug: Corticosteroids
A minimum dose of 5 mg prednisolon or equivalent

Drug: Simulect
Lyophilisate in vials with ampoules of sterile water for injection (5 mL), one vial containing 20 mg lyophilisate given intravenously on the day of transplantation and on day four post-transplantation.
Other Name: Basiliximab

Experimental: CycA+Certican Drug: Everolimus
Other Name: Certican

Drug: Cyclosporin A
Capsules: 10 mg, 25 mg, 50 mg or 100 mg. Transplantation to month 2: 75 - 125 ng/ml, month 3 to month 12: 50 - 100 ng/ml

Drug: Corticosteroids
A minimum dose of 5 mg prednisolon or equivalent

Drug: Simulect
Lyophilisate in vials with ampoules of sterile water for injection (5 mL), one vial containing 20 mg lyophilisate given intravenously on the day of transplantation and on day four post-transplantation.
Other Name: Basiliximab




Primary Outcome Measures :
  1. Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens [ Time Frame: One year post transplant ]

    To demonstrate non-inferiority in renal function assessed by glomerular filtration rate (Nankivell formula) in at least one of the Certican® treatment regimens compared to the standard regimen group at month 12 post-transplantation in renal transplant patients. Nankivell formula:

    GFR = 6.7/Scr + BW/4 - Surea/2 - 100/(height)² + C where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kg, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. The eGFR is expressed in mL/min per 1.73m². If a patient was on dialysis at the time of urea or creatinine assessment, the eGFR was set to 0. Analysis set = per protocol set



Secondary Outcome Measures :
  1. Percentage of Participants With Composite Treatment Failure Endpoints - Difference Between Groups at Month 12 [ Time Frame: Month 12 post transplant ]
    Combined endpoint included: biopsy proven acute rejection (BPAR) defined as a rejection which was acute and proven by biopsy, graft loss (GL) defined as: allograft was presumed to be lost on the day the patient starts dialysis and not able to be removed from dialysis or death. Patients who prematurely discontinued the study: if the patient did not suffer from an event before discontinuation and reason was not related to efficacy, the patient was assessed as having had no event, otherwise the patient was assessed as having had an event. Full analysis set (FAS)

  2. Glomular Filtration Rate (GFR) Via Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Method at Month 12 Post Transplant [ Time Frame: Month 12 post transplant ]
    Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method = GFR=141 x min(Scr/κ, 1)α x max(Scr/κ, 1)1.209 x 0.993Age x 1.018 [if female] x 1.159 [if black] where Scr is serum creatinine, κ is 0.7 for females and 0.9 for males, α is 0.329 for females and 0.411 for males, min indicates the minimum of Scr/κ or 1, and max indicates the maximum of Scr/κ or 1. last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model

  3. Glomular Filtration Rate (GFR) mL/Min Via Cockcroft- Gault Method at Month 12 Post Transplant [ Time Frame: Month 12 post transplant ]
    Cockcroft-Gault formula: For men: GFR= ((140-age) × body weight in kg)∕(72 x serum creatinine in mg∕dl)For women: GFR= (0.85×(140-age) × body weight in kg)∕(72 x serum creatinine in mg/dl), ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model

  4. Glomular Filtration Rate (GFR) Via Modification of Diet in Renal Disease (MDRD) Method at Month 12 Post Transplant [ Time Frame: Month 12 post transplant ]
    Modification of Diet in Renal Disease (MDRD) = For men: GFR = 170 x (serum creatinine -0,999) x (age-0,176) x (urea nitrogen -0,17) x (albumin0,318) For women: GFR = 170 x (serum creatinine -0,999) x (age-0,176) x (urea nitrogen -0,17) x albumin0,318) x 0.762 with urea nitrogen = urea / 2.144. last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model

  5. Percentage of Participants With Treatment Failure Endpoints at Month 12 [ Time Frame: Month 12 post transplant ]
    Treatment failure endpoints: biopsy proven acute rejection (BPAR) defined as a rejection which was acute and proven by biopsy, graft loss (GL) defined as: allograft was presumed to be lost on the day the patient starts dialysis and not able to be removed from dialysis or death. Patients who prematurely discontinued the study: if the patient did not suffer from an event before discontinuation and reason was not related to efficacy, the patient was assessed as having had no event, otherwise the patient was assessed as having had an event. Full analysis set (FAS)

  6. Percent of Participants With Delayed Graft Function and Slow Graft Function [ Time Frame: Post transplant to month 12 ]
    Delayed graft function (DGF) was defined as the need for dialysis within the first 7 days post-transplantation, excluding the first post-transplantation day. Slow graft function (SGF) was defined as a serum creatinine >3.0 mg/dL at Day 5 post-transplantation. Full analysis set

  7. Percent of Participants With Delayed Graft Function by Day [ Time Frame: Post transplant up to day 7 ]
    Delayed graft function (DGF) was defined as the need for dialysis within the first 7 days post-transplantation, excluding the first post-transplantation day.

  8. Percent of Participants With Viral Infections [ Time Frame: Post transplant to month 12 ]
    Viral infections for BKV Virus Humane Polyomavirus 1 and Cytomegalovirus

  9. Percent of Participants With Wound Healing Complications During Study [ Time Frame: Post transplant until individual reporting ]
    Information collected to report wound healing process which included percentage of participants with complications, fluid collections detected and occurrence of lymphoceles

  10. Duration of Wound Healing [ Time Frame: Post transplant until individual reporting ]
    A wound will be considered healed if all the suture material and staples are removed and the wound is intact. Number of participants is based on all patients of the respective treatment group in the safety set, excluding patients with no answer (unknown).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient who had received a primary or secondary kidney transplant
  • Patients who were willing and from whom written informed consent was obtained
  • kidney allograft with a cold ischemia time (CIT) < 30 hours
  • negative pregnancy test prior to study enrollment

Exclusion Criteria:

--Multi-organ recipients

  • former Graft loss due to immunological reasons
  • Patients who received a kidney from a non-heart beating donor
  • A-B-0 incompatible transplants
  • a current Panel Reactive Antibody (PRA) level of > 20%
  • existing antibodies against the HLA-type of the receiving transplant
  • a known hypersensitivity/contraindication to any of the immunosuppressants
  • Use of other investigational drugs
  • Patients with thrombocytopenia (platelets < 100,000/mm³), with an absolute neutrophil count of < 2,000/mm³ or leucopenia (leucocytes < 3,000/mm³), or hemoglobin < 8 g/dL
  • significant mental illness
  • history of malignancy during the last five years
  • HIV positive
  • uncontrolled hypercholesterolemia or hypertriglyceridemia
  • drug or alcohol abuse
  • pregnant or breast feeding women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01843348


Locations
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France
Novartis Investigative Site
Bordeaux Cedex, France, 33076
Novartis Investigative Site
Brest, France, 29200
Novartis Investigative Site
Creteil, France, 94010
Novartis Investigative Site
Dijon, France, 21079
Novartis Investigative Site
Lille Cedex, France, 59037
Novartis Investigative Site
Lyon, France, 69437
Novartis Investigative Site
Nantes, France, 44035
Novartis Investigative Site
Paris, France, 75970
Novartis Investigative Site
Poitiers, France, 86000
Novartis Investigative Site
St Priest en Jarez Cedex, France, 42277
Novartis Investigative Site
Strasbourg, France, 67091
Novartis Investigative Site
Toulouse Cedex 4, France, 31054
Germany
Novartis Investigative Site
Aachen, Germany, 52074
Novartis Investigative Site
Berlin, Germany, 13353
Novartis Investigative Site
Bochum, Germany, 44892
Novartis Investigative Site
Dresden, Germany, 01307
Novartis Investigative Site
Erlangen, Germany, 91052
Novartis Investigative Site
Essen, Germany, 45147
Novartis Investigative Site
Frankfurt, Germany, 60590
Novartis Investigative Site
Freiburg, Germany, 79106
Novartis Investigative Site
Hamburg, Germany, 20246
Novartis Investigative Site
Hannover, Germany, 30625
Novartis Investigative Site
Heidelberg, Germany, 69120
Novartis Investigative Site
Kiel, Germany, 24105
Novartis Investigative Site
Mainz, Germany, 55131
Novartis Investigative Site
Muenster, Germany, 48149
Novartis Investigative Site
Tübingen, Germany, 72076
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01843348    
Other Study ID Numbers: CRAD001ADE44
2011-005238-21 ( EudraCT Number )
First Posted: April 30, 2013    Key Record Dates
Results First Posted: May 1, 2017
Last Update Posted: May 1, 2017
Last Verified: March 2017
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Transplant
Renal transplant
Rejection,allograf
Rejection
Xenograft rejection
Host vs graft disease
Kidney Transplant
Additional relevant MeSH terms:
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Sirolimus
Mycophenolic Acid
Cyclosporine
Everolimus
Tacrolimus
Cyclosporins
Basiliximab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Dermatologic Agents
Antirheumatic Agents
Antibiotics, Antitubercular
Antitubercular Agents