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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01950819
Other study ID # CRAD001A2433
Secondary ID 2013-000322-66
Status Completed
Phase Phase 4
First received
Last updated
Start date December 3, 2013
Est. completion date January 17, 2018

Study information

Verified date January 2019
Source Novartis
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a 2-year, randomized, multicenter, open-label, 2-arm study evaluating the graft function of everolimus and reduced CNI versus MPA and standard CNI in adult de novo renal transplant recipients.


Other known NCT identifiers
  • NCT02316938

Recruitment information / eligibility

Status Completed
Enrollment 2037
Est. completion date January 17, 2018
Est. primary completion date February 1, 2017
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

1. Written informed consent obtained.

2. Subject randomized within 24 hr of completion of transplant surgery.

3. Recipient of a kidney with a cold ischemia time < 30 hours.

4. Recipient of a primary (or secondary, if first graft is not lost due to immunological reasons) renal transplant from a deceased heart beating, living unrelated, living related non-human leukocyte antigen identical or an expanded criteria donor.

Exclusion Criteria:

1. Subject unable to tolerate oral medication at time of randomization.

2. Use of other investigational drugs at the time of enrollment.

3. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.

4. Multi-organ transplant recipient.

5. Recipient of ABO incompatible allograft or complement-dependent lymphocytotoxic (CDC) crossmatch positive transplant.

6. Subject at high immunological risk for rejection as determined by local practice for assessment of anti-donor reactivity e.g. high PRA, presence of pre-existing DSA.

7. Subject who is HIV-positive.

8. HBsAg and/or a HCV positive subject with evidence of elevated LFTs (ALT/AST levels = 2.5 times ULN). Viral serology results obtained within 6 months prior to randomization are acceptable.

9. Recipient of a kidney from a donor who tests positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV).

10. Subject with a BMI greater than 35.

11. Subject with severe systemic infections, current or within the two weeks prior to randomization.

12. Subject requiring systemic anticoagulation.

13. History of malignancy of any organ system.

14. Subject with severe restrictive or obstructive pulmonary disorders.

15. Subject with severe hypercholesterolemia or hypertriglyceridemia that cannot be controlled.

16. Subject with white blood cell (WBC) count = 2,000 /mm3 or with platelet count = 50,000 /mm3.

17. Pregnant or nursing (lactating) women.

18. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.

Study Design


Intervention

Biological:
Induction therapy
All subjects received induction therapy with basiliximab or rabbit anti-thymocyte globulin, in the peritransplant period.
Drug:
Corticosteroids
All subjects received maintenance therapy with corticosteroids throughout the 24 month study period. A minimum dose of 5 mg prednisone, or equivalent, per day was maintained.
EVR+rCNI
Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)
MPA+sCNI
Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).

Locations

Country Name City State
Argentina Novartis Investigative Site Buenos Aires
Argentina Novartis Investigative Site Caba Buenos Aires
Argentina Novartis Investigative Site Cordoba
Argentina Novartis Investigative Site Cordoba
Argentina Novartis Investigative Site Corrientes
Argentina Novartis Investigative Site San Martin Buenos Aires
Argentina Novartis Investigative Site Santa Fe
Australia Novartis Investigative Site Adelaide South Australia
Australia Novartis Investigative Site Camperdown New South Wales
Australia Novartis Investigative Site Clayton Victoria
Australia Novartis Investigative Site Heidelberg Victoria
Australia Novartis Investigative Site Murdoch Western Australia
Australia Novartis Investigative Site Nedlands Western Australia
Australia Novartis Investigative Site Parkville Victoria
Australia Novartis Investigative Site Randwick New South Wales
Australia Novartis Investigative Site Westmead New South Wales
Australia Novartis Investigative Site Woolloongabba Queensland
Austria Novartis Investigative Site Innsbruck Tyrol
Austria Novartis Investigative Site Linz
Belgium Novartis Investigative Site Bruxelles
Belgium Novartis Investigative Site Edegem Antwerpen
Belgium Novartis Investigative Site Leuven
Belgium Novartis Investigative Site Liege
Brazil Novartis Investigative Site Porto Alegre RS
Brazil Novartis Investigative Site Sao Paulo SP
Brazil Novartis Investigative Site São Paulo SP
Bulgaria Novartis Investigative Site Sofia BGR
Chile Novartis Investigative Site Santiago
Colombia Novartis Investigative Site Bogota
Colombia Novartis Investigative Site Cali Valle Del Cauca
Croatia Novartis Investigative Site Rijeka
Croatia Novartis Investigative Site Zagreb
Croatia Novartis Investigative Site Zagreb
Czechia Novartis Investigative Site Brno
Czechia Novartis Investigative Site Praha 4
Egypt Novartis Investigative Site Mansoura
France Novartis Investigative Site Montpellier Cedex 5
France Novartis Investigative Site Nice Cedex1
France Novartis Investigative Site Paris cedex 15
France Novartis Investigative Site Reims
France Novartis Investigative Site Tours Cedex 9 Indre Et Loire
Germany Novartis Investigative Site Berlin
Germany Novartis Investigative Site Berlin
Germany Novartis Investigative Site Essen
Germany Novartis Investigative Site Hannover
Germany Novartis Investigative Site Hannover Muenden
Germany Novartis Investigative Site Heidelberg
Germany Novartis Investigative Site Kaiserslautern
Germany Novartis Investigative Site Koeln
Germany Novartis Investigative Site Leipzig
Germany Novartis Investigative Site Muenchen
Germany Novartis Investigative Site München
Germany Novartis Investigative Site Regensburg Bavaria
Greece Novartis Investigative Site Athens
Greece Novartis Investigative Site Athens
Greece Novartis Investigative Site Patras
Greece Novartis Investigative Site Thessaloniki GR
India Novartis Investigative Site Bangalore Karnataka
India Novartis Investigative Site Mumbai Maharashtra
India Novartis Investigative Site New Delhi Delhi
India Novartis Investigative Site Vellore Tamil Nadu
Israel Novartis Investigative Site Petach Tikva
Israel Novartis Investigative Site Tel Aviv
Italy Novartis Investigative Site Bari BA
Italy Novartis Investigative Site Bologna BO
Italy Novartis Investigative Site Milano MI
Italy Novartis Investigative Site Novara
Italy Novartis Investigative Site Padova PD
Italy Novartis Investigative Site Parma PR
Italy Novartis Investigative Site Roma RM
Italy Novartis Investigative Site Roma RM
Italy Novartis Investigative Site Siena SI
Italy Novartis Investigative Site Torino TO
Japan Novartis Investigative Site Chiba-city Chiba
Japan Novartis Investigative Site Nagoya-city Aichi
Japan Novartis Investigative Site Toyoake city Aichi
Korea, Republic of Novartis Investigative Site Seoul Korea
Korea, Republic of Novartis Investigative Site Seoul Korea
Korea, Republic of Novartis Investigative Site Seoul
Kuwait Novartis Investigative Site Kuwait
Lebanon Novartis Investigative Site Ashrafieh
Lebanon Novartis Investigative Site Saida
Lebanon Novartis Investigative Site Saida
Malaysia Novartis Investigative Site Kuala Lumpur
Malaysia Novartis Investigative Site Selangor Darul Ehsan
Mexico Novartis Investigative Site Guadalajara Jalisco
Netherlands Novartis Investigative Site Amsterdam
Netherlands Novartis Investigative Site Groningen
Netherlands Novartis Investigative Site Leiden
Netherlands Novartis Investigative Site Maastricht AZ
Netherlands Novartis Investigative Site Nijmegen
Netherlands Novartis Investigative Site Utrecht The Netherlands
Norway Novartis Investigative Site Oslo
Philippines Novartis Investigative Site Quezon City
Poland Novartis Investigative Site Gdansk
Poland Novartis Investigative Site Poznan
Poland Novartis Investigative Site Poznan
Poland Novartis Investigative Site Szczecin Pomorskie
Portugal Novartis Investigative Site Carnaxide Lisboa
Portugal Novartis Investigative Site Coimbra
Portugal Novartis Investigative Site Lisboa
Portugal Novartis Investigative Site Lisbon
Portugal Novartis Investigative Site Porto
Russian Federation Novartis Investigative Site Ekaterinburg
Russian Federation Novartis Investigative Site Krasnodar
Russian Federation Novartis Investigative Site Moscow
Russian Federation Novartis Investigative Site Moscow
Russian Federation Novartis Investigative Site Nizhnii Novgorod
Russian Federation Novartis Investigative Site Volzhskiy
Saudi Arabia Novartis Investigative Site Dammam
Saudi Arabia Novartis Investigative Site Jeddah
Saudi Arabia Novartis Investigative Site Riyadh
Serbia Novartis Investigative Site Belgrade
Serbia Novartis Investigative Site Nis
Serbia Novartis Investigative Site Novi Sad
Singapore Novartis Investigative Site Singapore
Slovakia Novartis Investigative Site Banská Bystrica
Slovakia Novartis Investigative Site Bratislava
Slovakia Novartis Investigative Site Kosice
Slovakia Novartis Investigative Site Martin
Slovenia Novartis Investigative Site Ljubljana
South Africa Novartis Investigative Site Cape Town Western Province
Spain Novartis Investigative Site Barcelona Catalunya
Spain Novartis Investigative Site Barcelona Catalunya
Spain Novartis Investigative Site Granada Andalucia
Spain Novartis Investigative Site Hospitalet de Llobregat Barcelona
Spain Novartis Investigative Site La Laguna Santa Cruz De Tenerife
Spain Novartis Investigative Site Madrid
Spain Novartis Investigative Site Madrid
Spain Novartis Investigative Site Santander Cantabria
Spain Novartis Investigative Site Valencia Comunidad Valenciana
Spain Novartis Investigative Site Zaragoza
Sweden Novartis Investigative Site Göteborg
Sweden Novartis Investigative Site Stockholm
Sweden Novartis Investigative Site Uppsala
Switzerland Novartis Investigative Site Bern
Taiwan Novartis Investigative Site Taichung
Taiwan Novartis Investigative Site Tainan Taiwan ROC
Taiwan Novartis Investigative Site Taipei
Thailand Novartis Investigative Site Bangkok
Thailand Novartis Investigative Site Ratchathewi Bangkok
Turkey Novartis Investigative Site Antalya
Turkey Novartis Investigative Site Istanbul
Turkey Novartis Investigative Site Mecidiyekoy/Istanbul
United States Novartis Investigative Site Ann Arbor Michigan
United States Novartis Investigative Site Aurora Colorado
United States Novartis Investigative Site Baltimore Maryland
United States Novartis Investigative Site Birmingham Alabama
United States Novartis Investigative Site Boston Massachusetts
United States Novartis Investigative Site Boston Massachusetts
United States Novartis Investigative Site Bronx New York
United States Novartis Investigative Site Buffalo New York
United States Novartis Investigative Site Burlington Massachusetts
United States Novartis Investigative Site Chapel Hill North Carolina
United States Novartis Investigative Site Charleston South Carolina
United States Novartis Investigative Site Charlottesville Virginia
United States Novartis Investigative Site Chicago Illinois
United States Novartis Investigative Site Cleveland Ohio
United States Novartis Investigative Site Cleveland Ohio
United States Novartis Investigative Site Columbus Ohio
United States Novartis Investigative Site Dallas Texas
United States Novartis Investigative Site Denver Colorado
United States Novartis Investigative Site Detroit Michigan
United States Novartis Investigative Site Durham North Carolina
United States Novartis Investigative Site Fort Worth Texas
United States Novartis Investigative Site Harrisburg Pennsylvania
United States Novartis Investigative Site Houston Texas
United States Novartis Investigative Site Houston Texas
United States Novartis Investigative Site Livingston New Jersey
United States Novartis Investigative Site Loma Linda California
United States Novartis Investigative Site Los Angeles California
United States Novartis Investigative Site Los Angeles California
United States Novartis Investigative Site Madison Wisconsin
United States Novartis Investigative Site Milwaukee Wisconsin
United States Novartis Investigative Site Nashville Tennessee
United States Novartis Investigative Site Providence Rhode Island
United States Novartis Investigative Site Sacramento California
United States Novartis Investigative Site Saint Louis Missouri
United States Novartis Investigative Site Salt Lake City Utah
United States Novartis Investigative Site San Diego California
United States Novartis Investigative Site San Francisco California
United States Novartis Investigative Site San Francisco California
United States Novartis Investigative Site Seattle Washington
United States Novartis Investigative Site Winston-Salem North Carolina

Sponsors (1)

Lead Sponsor Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Chile,  Colombia,  Croatia,  Czechia,  Egypt,  France,  Germany,  Greece,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Kuwait,  Lebanon,  Malaysia,  Mexico,  Netherlands,  Norway,  Philippines,  Poland,  Portugal,  Russian Federation,  Saudi Arabia,  Serbia,  Singapore,  Slovakia,  Slovenia,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  Thailand,  Turkey, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2. Incidence of failure on the composite of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73m2. Month 12 is Primary, Month 24 secondary
Secondary Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death Incidence of failure on the composite of (treated biopsy proven acute rejection (tBPAR), graft loss or death Month 12 and 24
Secondary Incidence of Failure on the Composite Endpoint of tBPAR, Graft Loss, Death or eGFR < 50 mL/Min/1.73m2 Incidence of failure on the composite endpoint of tBPAR, graft loss, death or eGFR < 50 mL/min/1.73m2 Month 12 and 24
Secondary Incidence of Failure on the Composite Endpoint of Graft Loss or Death. Incidence of failure on the composite endpoint of graft loss or death. Month 12 and 24
Secondary Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection Incidence of death, graft loss, tBPAR (treated biopsy proven acute rejection), BPAR (biopsy proven acute rejection), tAR (treated acute rejection), AR (acute rejection) and humoral rejection (aAMR : active antibody mediated rejection and cAMR: chronic antibody mediated rejection) Month 12 and 24
Secondary Incidence of eGFR < 50 mL/Min/1.73m2 Incidence of eGFR < 50 mL/min/1.73m2 Month 12 and 24
Secondary Renal Allograft Function : Mean Estimated Glomerular Filtration Rate, eGFR Renal allograft function : mean estimated glomerular filtration rate, eGFR Baseline (week 4), Month 12 and 24
Secondary Evolution of Renal Function, as eGFR, Over Time by Slope Analysis. Rate of change of renal function, as eGFR, calculated using MDRD4 formula (Coresh, 2003) and adjusted by covariates. Month 12 and 24
Secondary Renal Function Assessed by Creatinine Lab Values Mean Renal function as assessed in clinical practice, by ceatinine values. Analysis is done without considering missing values for analysis. Month 12 and 24
Secondary Renal Function by Alternative Formulae (e.g. CKD-EPI). eGFR Values Reported Mean Renal function as used in clinical practice, using different formula for calculation of renal function than MDRD4 (our primary efficacy parameter), and other alternate formulae (e.g. CKD-EPI). Analysis is done without considering missing values for analysis. Month 12 and 24
Secondary Incidence of Adverse Events, Serious Adverse Events and Adverse Events Leading to Study Regimen Discontinuation. Incidence of adverse events, serious adverse events and adverse events leading to study regimen discontinuation. Month 24
Secondary Incidence of Cytomegalovirus and BK Virus, New Onset Diabetes Mellitus, Chronic Kidney Disease With Associated Proteinuria and Calcineurin Inhibitor Associated Adverse Events. Incidence of cytomegalovirus and BK virus, new onset diabetes mellitus, chronic kidney disease with associated proteinuria and calcineurin inhibitor associated adverse events. Month 24
Secondary Urinary Protein and Albumin Excretion by Treatment Estimated by Urinary Protein/Creatinine and Urinary Albumin/Creatinine Ratios. Mean urinary protein and albumin excretion by treatment estimated by mean urinary protein/creatinine and urinary albumin/creatinine ratios. Baseline, Month 12 and 24
Secondary Incidence of Major Cardiovascular Events. Incidence of major cardiovascular events by Preferred Term Month 24
Secondary Incidence of Malignancies. Incidence of malignancies. Month 24
Secondary Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2 Among Compliant Subjects. Incidence of failure on the composite of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73m2 among compliant subjects. Month 12 and 24
Secondary Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Participants) Incidence tBPAR, defined as any condition where the subject received anti-rejection treatment and was histologically diagnosed as acute rejection (according to the Banff 2009 criteria), by severity (grade IA, IB, IIA, IIB, III) and time to event. Grades for T-cell mediated rejection, with increasing severity:
Type IA - Significant interstitial infiltration (> 25% of parenchyma) and foci of moderate tubulitis (> 4 mononuclear cells/tubular cross section or group of 10 tubular cells).
Type IB - Significant interstitial infiltration (> 25% of parenchyma) and foci of severe tubulitis (> 10 mononuclear cells/tubular cross section or group of 10 tubular cells).
Type IIA - Mild to moderate intimal arteritis
Type IIB - Severe intimal arteritis comprising > 25% of the lumenal area
Type III - Transmural (full vessel wall thickness) arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (with accompanying lymphocytic inflammation)
Month 12 and 24
Secondary Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Events) Incidence tBPAR, defined as any condition where the subject received anti-rejection treatment and was histologically diagnosed as acute rejection (according to the Banff 2009 criteria), by severity (grade IA, IB, IIA, IIB, III) and time to event. Grades for T-cell mediated rejection, with increasing severity:
Type IA - Significant interstitial infiltration (> 25% of parenchyma) and foci of moderate tubulitis (> 4 mononuclear cells/tubular cross section or group of 10 tubular cells).
Type IB - Significant interstitial infiltration (> 25% of parenchyma) and foci of severe tubulitis (> 10 mononuclear cells/tubular cross section or group of 10 tubular cells).
Type IIA - Mild to moderate intimal arteritis
Type IIB - Severe intimal arteritis comprising > 25% of the lumenal area
Type III - Transmural (full vessel wall thickness) arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (with accompanying lymphocytic inflammation)
Month 12 and 24
Secondary Incidence of tBPAR (Treated Biopsy-proven Acute Rejection) Excluding Grade IA Rejections Incidence of tBPAR, defined as any condition where the subject received anti-rejection treatment and was histologically diagnosed as acute rejection (according to the Banff 2009 criteria), excluding grade IA rejections. Grades for T-cell mediated rejection, with increasing severity:
Type IA - Significant interstitial infiltration (> 25% of parenchyma) and foci of moderate tubulitis (> 4 mononuclear cells/tubular cross section or group of 10 tubular cells).
Type IB - Significant interstitial infiltration (> 25% of parenchyma) and foci of severe tubulitis (> 10 mononuclear cells/tubular cross section or group of 10 tubular cells).
Type IIA - Mild to moderate intimal arteritis
Type IIB - Severe intimal arteritis comprising > 25% of the lumenal area
Type III - Transmural (full vessel wall thickness) arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (with accompanying lymphocytic inflammation)
Month 12 and 24
Secondary Incidence of Composite of tBPAR (Treated Biopsy-proven Acute Rejection)or eGRF<50 mL/Min/1.73m2 by Subgroup Incidence of composite of tBPAR or eGRF<50 mL/min/1.73m2 by subgroup Month 12 and 24
Secondary Incidence of tBPAR (Excluding Grade IA Rejections) or GFR<50 mL/Min/1.73m2 Incidence of tBPAR (excluding grade IA rejections) or GFR<50 mL/min/1.73m2 Month 12 and 24
Secondary Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death or Loss to Follow-up Incidence of failure on the composite of (treated biopsy proven acute rejection (tBPAR), graft loss or death or loss to follow-up Month 12 and 24
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