PMID- 32406111
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20230124
IS  - 1600-6143 (Electronic)
IS  - 1600-6135 (Linking)
VI  - 21
IP  - 1
DP  - 2021 Jan
TI  - Three-year outcomes from the CRADLE study in de novo pediatric kidney transplant 
      recipients receiving everolimus with reduced tacrolimus and early steroid 
      withdrawal.
PG  - 123-137
LID - 10.1111/ajt.16005 [doi]
AB  - CRADLE was a 36-month multicenter study in pediatric (>/=1 to <18 years) kidney 
      transplant recipients randomized at 4 to 6 weeks posttransplant to receive 
      everolimus + reduced-exposure tacrolimus (EVR + rTAC; n = 52) with corticosteroid 
      withdrawal at 6-month posttransplant or continue mycophenolate mofetil + 
      standard-exposure TAC (MMF + sTAC; n = 54) with corticosteroids. The incidence of 
      composite efficacy failure (biopsy-proven acute rejection [BPAR], graft loss, or 
      death) at month 36 was 9.8% vs 9.6% (difference: 0.2%; 80% confidence interval: 
      -7.3 to 7.7) for EVR + rTAC and MMF + sTAC, respectively, which was driven by 
      BPARs. Graft loss was low (2.1% vs 3.8%) with no deaths. Mean estimated 
      glomerular filtration rate at month 36 was comparable between groups (68.1 vs 
      67.3 mL/min/1.73 m(2) ). Mean changes (z-score) in height (0.72 vs 0.39; 
      P = .158) and weight (0.61 vs 0.82; P = .453) from randomization to month 36 were 
      comparable, whereas growth in prepubertal patients on EVR + rTAC was better 
      (P = .050) vs MMF + sTAC. The overall incidence of adverse events (AEs) and 
      serious AEs was comparable between groups. Rejection was the leading AE for study 
      drug discontinuation in the EVR + rTAC group. In conclusion, though AE-related 
      study drug discontinuation was higher, an EVR + rTAC regimen represents an 
      alternative treatment option that enables withdrawal of steroids as well as 
      reduction of CNIs for pediatric kidney transplant recipients. ClinicalTrials.gov: 
      NCT01544491.
CI  - (c) 2020 The Authors. American Journal of Transplantation published by Wiley 
      Periodicals LLC on behalf of The American Society of Transplantation and the 
      American Society of Transplant Surgeons.
FAU - Tonshoff, Burkhard
AU  - Tonshoff B
AUID- ORCID: 0000-0002-6598-6910
AD  - Department of Pediatrics I, University Children's Hospital Heidelberg, 
      Heidelberg, Germany.
FAU - Tedesco-Silva, Helio
AU  - Tedesco-Silva H
AUID- ORCID: 0000-0002-9896-323X
AD  - Nephrology Division, Hospital do Rim, UNIFESP, Sao Paulo, Brazil.
FAU - Ettenger, Robert
AU  - Ettenger R
AD  - Division of Pediatric Nephrology, UCLA Mattel Children's Hospital, Los Angeles, 
      California, USA.
FAU - Christian, Martin
AU  - Christian M
AD  - Department of Pediatric Nephrology, Nottingham Children's Hospital, Nottingham, 
      UK.
FAU - Bjerre, Anna
AU  - Bjerre A
AD  - Division of Pediatric and Adolescent Medicine, Department of Pediatrics, Oslo 
      University Hospital, Oslo, Norway.
FAU - Dello Strologo, Luca
AU  - Dello Strologo L
AD  - Nephrology Unit, Department of Pediatrics, Institute for Scientific Research, 
      Bambino Gesu Children's Hospital, Rome, Italy.
FAU - Marks, Stephen D
AU  - Marks SD
AD  - Department of Pediatric Nephrology, Great Ormond Street Hospital for Children, 
      NHS Foundation Trust and University College London Great Ormond Street Institute 
      of Child Health, NIHR Great Ormond Street Hospital Biomedical Research Centre, 
      London, UK.
FAU - Pape, Lars
AU  - Pape L
AUID- ORCID: 0000-0002-3635-6418
AD  - Department of Pediatric Nephrology, Hannover Medical School, Hannover, Germany.
FAU - Veldandi, Udaykiran
AU  - Veldandi U
AD  - Novartis Healthcare Pvt. Ltd., Hyderabad, India.
FAU - Lopez, Patricia
AU  - Lopez P
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Cousin, Marc
AU  - Cousin M
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Pandey, Priti
AU  - Pandey P
AD  - Novartis Healthcare Pvt. Ltd., Hyderabad, India.
FAU - Meier, Matthias
AU  - Meier M
AD  - Novartis Pharma AG, Basel, Switzerland.
LA  - eng
SI  - ClinicalTrials.gov/NCT01544491
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200627
PL  - United States
TA  - Am J Transplant
JT  - American journal of transplantation : official journal of the American Society of 
      Transplantation and the American Society of Transplant Surgeons
JID - 100968638
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Steroids)
RN  - 9HW64Q8G6G (Everolimus)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
CIN - Am J Transplant. 2021 Jan;21(1):11-12. PMID: 32580235
MH  - Child
MH  - Everolimus
MH  - Glomerular Filtration Rate
MH  - Graft Rejection/drug therapy/etiology/prevention & control
MH  - Graft Survival
MH  - Humans
MH  - Immunosuppressive Agents
MH  - *Kidney Transplantation/adverse effects
MH  - Mycophenolic Acid/therapeutic use
MH  - Steroids
MH  - *Tacrolimus
MH  - Transplant Recipients
OTO - NOTNLM
OT  - clinical research/practice
OT  - glomerular filtration rate (GFR)
OT  - graft survival
OT  - immunosuppressant-mechanistic target of rapamycin: everolimus
OT  - immunosuppressive regimens-minimization/withdrawal
OT  - kidney transplantation/nephrology
OT  - patient safety
EDAT- 2020/05/15 06:00
MHDA- 2021/06/22 06:00
CRDT- 2020/05/15 06:00
PHST- 2019/10/03 00:00 [received]
PHST- 2020/04/27 00:00 [revised]
PHST- 2020/04/30 00:00 [accepted]
PHST- 2020/05/15 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/05/15 06:00 [entrez]
AID - S1600-6135(22)08323-X [pii]
AID - 10.1111/ajt.16005 [doi]
PST - ppublish
SO  - Am J Transplant. 2021 Jan;21(1):123-137. doi: 10.1111/ajt.16005. Epub 2020 Jun 
      27.