PMID- 23422495
OWN - NLM
STAT- MEDLINE
DCOM- 20130708
LR  - 20161125
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 95
IP  - 7
DP  - 2013 Apr 15
TI  - Randomized trial of everolimus-facilitated calcineurin inhibitor minimization 
      over 24 months in renal transplantation.
PG  - 933-42
LID - 10.1097/TP.0b013e3182848e03 [doi]
AB  - BACKGROUND: Strategies allowing calcineurin inhibitor minimization while 
      maintaining efficacy may improve renal transplant outcomes. METHODS: A2309 was a 
      24-month, phase IIIb, open-label trial of 833 de novo renal transplant recipients 
      randomized to everolimus, targeting trough concentrations of 3-8 or 6-12 ng/mL 
      plus reduced-exposure cyclosporine A (CsA) or to mycophenolic acid (MPA) 1.44 g 
      per day plus standard-exposure CsA. All patients received basiliximab +/- 
      corticosteroids. The incidence of the primary composite efficacy endpoint and its 
      components (treated biopsy-proven acute rejection, graft loss, death, or loss to 
      follow-up), renal function (serum creatinine and estimated glomerular filtration 
      rate), and adverse events (AEs) were compared at 24 months; as per the protocol, 
      these analyses were not noninferiority. RESULTS: Composite efficacy failure rates 
      (95% confidence interval for difference vs. MPA) were 32.9% (-2.2%, 13.0%), 26.9% 
      (-7.9%, 6.8%), and 27.4% at month 24 in the everolimus 3-8 and 6-12 ng/mL and MPA 
      groups, respectively. Mean estimated glomerular filtration rate (Modification of 
      Diet in Renal Disease) at month 24 was 52.2 (-2.1, 5.5 mL/min/1.73 m(2)), 49.4 
      (-4.8, 2.7 mL/min/1.73 m(2)), and 50.5 mL/min/1.73 m(2), respectively. AEs were 
      generally mild to moderate in severity and comparable between the groups. AEs 
      leading to discontinuation were reported in 28.5% (P = 0.03 vs. MPA), 30.6% (P = 
      0.007 vs. MPA), and 20.5% of patients receiving everolimus 3-8 and 6-12 ng/mL and 
      MPA, respectively. CONCLUSIONS: Everolimus trough concentrations targeted to 3-8 
      ng/mL, along with a greater than 60% reduction in CsA exposure, was associated 
      with comparable efficacy and renal function versus MPA plus standard-exposure CsA 
      over the 2-year period. A significantly higher incidence of AEs led to 
      discontinuation in the everolimus groups compared with the MPA group.
FAU - Cibrik, Diane
AU  - Cibrik D
AD  - Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. 
      dcibrik@umich.edu
FAU - Silva, Helio Tedesco Jr
AU  - Silva HT Jr
FAU - Vathsala, Anantharaman
AU  - Vathsala A
FAU - Lackova, Eva
AU  - Lackova E
FAU - Cornu-Artis, Catherine
AU  - Cornu-Artis C
FAU - Walker, Rowan G
AU  - Walker RG
FAU - Wang, Zailong
AU  - Wang Z
FAU - Zibari, Gazi B
AU  - Zibari GB
FAU - Shihab, Fuad
AU  - Shihab F
FAU - Kim, Yu S
AU  - Kim YS
LA  - eng
SI  - ClinicalTrials.gov/NCT00251004
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Adrenal Cortex Hormones)
RN  - 0 (Calcineurin Inhibitors)
RN  - 0 (Immunosuppressive Agents)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - 9HW64Q8G6G (Everolimus)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adrenal Cortex Hormones/therapeutic use
MH  - Adult
MH  - *Calcineurin Inhibitors
MH  - Cyclosporine/adverse effects/blood/*therapeutic use
MH  - Drug Monitoring
MH  - Drug Therapy, Combination
MH  - Everolimus
MH  - Female
MH  - Glomerular Filtration Rate/drug effects
MH  - Graft Rejection/immunology/mortality/physiopathology/*prevention & control
MH  - Graft Survival/drug effects
MH  - Humans
MH  - Immunosuppressive Agents/adverse effects/blood/*therapeutic use
MH  - Kaplan-Meier Estimate
MH  - Kidney Transplantation/adverse effects/*immunology/mortality
MH  - Male
MH  - Middle Aged
MH  - Mycophenolic Acid/analogs & derivatives/therapeutic use
MH  - Sirolimus/adverse effects/*analogs & derivatives/blood/therapeutic use
MH  - Time Factors
MH  - Treatment Outcome
EDAT- 2013/02/21 06:00
MHDA- 2013/07/09 06:00
CRDT- 2013/02/21 06:00
PHST- 2013/02/21 06:00 [entrez]
PHST- 2013/02/21 06:00 [pubmed]
PHST- 2013/07/09 06:00 [medline]
AID - 10.1097/TP.0b013e3182848e03 [doi]
PST - ppublish
SO  - Transplantation. 2013 Apr 15;95(7):933-42. doi: 10.1097/TP.0b013e3182848e03.