OSAKA Trial: A Randomized, Controlled Trial Comparing Tacrolimus QD and BD in Kidney Transplantation
Identifieur interne : 000197 ( Ncbi/Merge ); précédent : 000196; suivant : 000198OSAKA Trial: A Randomized, Controlled Trial Comparing Tacrolimus QD and BD in Kidney Transplantation
Auteurs : Laetitia Albano [France] ; Bernhard Banas [Allemagne] ; Juergen L. Klempnauer [Allemagne] ; Maciej Glyda [Pologne] ; Ondrej Viklicky [République tchèque] ; Nassim KamarSource :
- Transplantation [ 0041-1337 ] ; 2013.
Abstract
The once-daily (QD), prolonged-release formulation of tacrolimus has been shown to improve adherence versus twice-daily (BD) tacrolimus. Treatment nonadherence in transplant recipients has been associated with poor graft outcomes.
This open-label, parallel-group study randomized adults with end-stage renal disease undergoing primary kidney transplantation or retransplantation to an initial dose of tacrolimus BD 0.2 mg/kg per day (Arm 1; n=309), QD 0.2 mg/kg per day (Arm 2; n=302), QD 0.3 mg/kg per day (Arm 3; n=304) all with mycophenolate mofetil and corticosteroids (tapered) over 24 weeks, or tacrolimus QD 0.2 mg/kg per day with mycophenolate mofetil, basiliximab, and corticosteroids given only perioperatively (Arm 4; n=283). The primary composite endpoint (efficacy failure; per protocol set) was defined as graft loss, biopsy-confirmed acute rejection, or graft dysfunction at week 24. Graft dysfunction was defined as estimated glomerular filtration rate Modification of Diet in Renal Disease-4 formula of less than 40 mL/min/1.73 m2. The prespecified noninferiority margin was 12.5%.
The per protocol set included 976 patients: 237, 263, 246, and 230 patients in Arms 1 to 4, respectively. Noninferiority of the composite endpoint was demonstrated for Arm 2 versus Arm 1; Kaplan–Meier estimates of efficacy failure were 42.2% and 40.6%, respectively (difference, −1.6%; 95% confidence interval [CI], −12.2% to 9.0%). Noninferiority to Arm 1 was not confirmed for Arm 3 (difference, −3.5%; 95% CI, −13.6% to 6.6%) or Arm 4 (difference, −7.1%; 95% CI, −16.1% to 1.9%). Graft dysfunction (estimated glomerular filtration rate <40 mL/min/1.73 m2) was the main determinant of composite-endpoint efficacy failure across all arms.
In patients representative of the European kidney transplant population, tacrolimus QD-based immunosuppression (0.2 mg/kg/day), without induction, showed similar efficacy to 0.2 mg/kg per day tacrolimus BD.
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DOI: 10.1097/TP.0b013e3182a203bd
PubMed: 23982340
PubMed Central: 3864174
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">OSAKA Trial: A Randomized, Controlled Trial Comparing Tacrolimus QD and BD in Kidney Transplantation</title><author><name sortKey="Albano, Laetitia" sort="Albano, Laetitia" uniqKey="Albano L" first="Laetitia" last="Albano">Laetitia Albano</name><affiliation wicri:level="1"><nlm:aff id="aff1"> Department of Nephrology, Centre Hospitalier Universitaire de Nice, Nice, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea> Department of Nephrology, Centre Hospitalier Universitaire de Nice, Nice</wicri:regionArea><placeName><settlement type="city">Nice</settlement></placeName></affiliation></author><author><name sortKey="Banas, Bernhard" sort="Banas, Bernhard" uniqKey="Banas B" first="Bernhard" last="Banas">Bernhard Banas</name><affiliation wicri:level="1"><nlm:aff id="aff2"> Internal Medicine II-Nephrology, University Medical Center, Regensburg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea> Internal Medicine II-Nephrology, University Medical Center, Regensburg</wicri:regionArea><wicri:noRegion>Regensburg</wicri:noRegion><wicri:noRegion>Regensburg</wicri:noRegion><wicri:noRegion>Regensburg</wicri:noRegion></affiliation></author><author><name sortKey="Klempnauer, Juergen L" sort="Klempnauer, Juergen L" uniqKey="Klempnauer J" first="Juergen L." last="Klempnauer">Juergen L. Klempnauer</name><affiliation wicri:level="3"><nlm:aff id="aff3"> General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea> General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover</wicri:regionArea><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Hanovre</settlement></placeName></affiliation></author><author><name sortKey="Glyda, Maciej" sort="Glyda, Maciej" uniqKey="Glyda M" first="Maciej" last="Glyda">Maciej Glyda</name><affiliation wicri:level="1"><nlm:aff id="aff4"> Department of Transplantology and Surgery, District Public Hospital, Poznan, Poland.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pologne</country><wicri:regionArea> Department of Transplantology and Surgery, District Public Hospital, Poznan</wicri:regionArea><wicri:noRegion>Poznan</wicri:noRegion></affiliation></author><author><name sortKey="Viklicky, Ondrej" sort="Viklicky, Ondrej" uniqKey="Viklicky O" first="Ondrej" last="Viklicky">Ondrej Viklicky</name><affiliation wicri:level="3"><nlm:aff id="aff5"> Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République tchèque</country><wicri:regionArea> Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague</wicri:regionArea><placeName><settlement type="city">Prague</settlement><region type="région" nuts="2">Bohême centrale</region></placeName></affiliation></author><author><name sortKey="Kamar, Nassim" sort="Kamar, Nassim" uniqKey="Kamar N" first="Nassim" last="Kamar">Nassim Kamar</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23982340</idno><idno type="pmc">3864174</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864174</idno><idno type="RBID">PMC:3864174</idno><idno type="doi">10.1097/TP.0b013e3182a203bd</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000061</idno><idno type="wicri:Area/Pmc/Curation">000061</idno><idno type="wicri:Area/Pmc/Checkpoint">000256</idno><idno type="wicri:Area/Ncbi/Merge">000197</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">OSAKA Trial: A Randomized, Controlled Trial Comparing Tacrolimus QD and BD in Kidney Transplantation</title><author><name sortKey="Albano, Laetitia" sort="Albano, Laetitia" uniqKey="Albano L" first="Laetitia" last="Albano">Laetitia Albano</name><affiliation wicri:level="1"><nlm:aff id="aff1"> Department of Nephrology, Centre Hospitalier Universitaire de Nice, Nice, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea> Department of Nephrology, Centre Hospitalier Universitaire de Nice, Nice</wicri:regionArea><placeName><settlement type="city">Nice</settlement></placeName></affiliation></author><author><name sortKey="Banas, Bernhard" sort="Banas, Bernhard" uniqKey="Banas B" first="Bernhard" last="Banas">Bernhard Banas</name><affiliation wicri:level="1"><nlm:aff id="aff2"> Internal Medicine II-Nephrology, University Medical Center, Regensburg, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea> Internal Medicine II-Nephrology, University Medical Center, Regensburg</wicri:regionArea><wicri:noRegion>Regensburg</wicri:noRegion><wicri:noRegion>Regensburg</wicri:noRegion><wicri:noRegion>Regensburg</wicri:noRegion></affiliation></author><author><name sortKey="Klempnauer, Juergen L" sort="Klempnauer, Juergen L" uniqKey="Klempnauer J" first="Juergen L." last="Klempnauer">Juergen L. Klempnauer</name><affiliation wicri:level="3"><nlm:aff id="aff3"> General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea> General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover</wicri:regionArea><placeName><region type="land" nuts="2">Basse-Saxe</region><settlement type="city">Hanovre</settlement></placeName></affiliation></author><author><name sortKey="Glyda, Maciej" sort="Glyda, Maciej" uniqKey="Glyda M" first="Maciej" last="Glyda">Maciej Glyda</name><affiliation wicri:level="1"><nlm:aff id="aff4"> Department of Transplantology and Surgery, District Public Hospital, Poznan, Poland.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pologne</country><wicri:regionArea> Department of Transplantology and Surgery, District Public Hospital, Poznan</wicri:regionArea><wicri:noRegion>Poznan</wicri:noRegion></affiliation></author><author><name sortKey="Viklicky, Ondrej" sort="Viklicky, Ondrej" uniqKey="Viklicky O" first="Ondrej" last="Viklicky">Ondrej Viklicky</name><affiliation wicri:level="3"><nlm:aff id="aff5"> Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République tchèque</country><wicri:regionArea> Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague</wicri:regionArea><placeName><settlement type="city">Prague</settlement><region type="région" nuts="2">Bohême centrale</region></placeName></affiliation></author><author><name sortKey="Kamar, Nassim" sort="Kamar, Nassim" uniqKey="Kamar N" first="Nassim" last="Kamar">Nassim Kamar</name></author></analytic><series><title level="j">Transplantation</title><idno type="ISSN">0041-1337</idno><idno type="eISSN">1534-6080</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>The once-daily (QD), prolonged-release formulation of tacrolimus has been shown to improve adherence versus twice-daily (BD) tacrolimus. Treatment nonadherence in transplant recipients has been associated with poor graft outcomes.</p></sec><sec><title>Methods</title><p>This open-label, parallel-group study randomized adults with end-stage renal disease undergoing primary kidney transplantation or retransplantation to an initial dose of tacrolimus BD 0.2 mg/kg per day (Arm 1; n=309), QD 0.2 mg/kg per day (Arm 2; n=302), QD 0.3 mg/kg per day (Arm 3; n=304) all with mycophenolate mofetil and corticosteroids (tapered) over 24 weeks, or tacrolimus QD 0.2 mg/kg per day with mycophenolate mofetil, basiliximab, and corticosteroids given only perioperatively (Arm 4; n=283). The primary composite endpoint (efficacy failure; per protocol set) was defined as graft loss, biopsy-confirmed acute rejection, or graft dysfunction at week 24. Graft dysfunction was defined as estimated glomerular filtration rate Modification of Diet in Renal Disease-4 formula of less than 40 mL/min/1.73 m<sup>2</sup>. The prespecified noninferiority margin was 12.5%.</p></sec><sec><title>Results</title><p>The per protocol set included 976 patients: 237, 263, 246, and 230 patients in Arms 1 to 4, respectively. Noninferiority of the composite endpoint was demonstrated for Arm 2 versus Arm 1; Kaplan–Meier estimates of efficacy failure were 42.2% and 40.6%, respectively (difference, −1.6%; 95% confidence interval [CI], −12.2% to 9.0%). Noninferiority to Arm 1 was not confirmed for Arm 3 (difference, −3.5%; 95% CI, −13.6% to 6.6%) or Arm 4 (difference, −7.1%; 95% CI, −16.1% to 1.9%). Graft dysfunction (estimated glomerular filtration rate <40 mL/min/1.73 m<sup>2</sup>) was the main determinant of composite-endpoint efficacy failure across all arms.</p></sec><sec><title>Conclusions</title><p>In patients representative of the European kidney transplant population, tacrolimus QD-based immunosuppression (0.2 mg/kg/day), without induction, showed similar efficacy to 0.2 mg/kg per day tacrolimus BD.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Schiff, J" uniqKey="Schiff J">J Schiff</name></author><author><name sortKey="Cole, E" uniqKey="Cole E">E Cole</name></author><author><name sortKey="Cantarovich, M" uniqKey="Cantarovich M">M Cantarovich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, Mj" uniqKey="Wu M">MJ Wu</name></author><author><name sortKey="Cheng, Cy" uniqKey="Cheng C">CY Cheng</name></author><author><name sortKey="Chen, Ch" 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Morales</name></author><author><name sortKey="Varo, E" uniqKey="Varo E">E Varo</name></author><author><name sortKey="Lazaro, P" uniqKey="Lazaro P">P Lázaro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kuypers, Dr" uniqKey="Kuypers D">DR Kuypers</name></author><author><name sortKey="Peeters, Pc" uniqKey="Peeters P">PC Peeters</name></author><author><name sortKey="Sennesael, Jj" uniqKey="Sennesael J">JJ Sennesael</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beckebaum, S" uniqKey="Beckebaum S">S Beckebaum</name></author><author><name sortKey="Jacob, S" uniqKey="Jacob S">S Jacob</name></author><author><name sortKey="Sweid, D" uniqKey="Sweid D">D Sweid</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wlodarczyk, Z" uniqKey="Wlodarczyk Z">Z Wlodarczyk</name></author><author><name sortKey="Squifflet, Jp" uniqKey="Squifflet J">JP Squifflet</name></author><author><name sortKey="Ostrowski, M" uniqKey="Ostrowski M">M Ostrowski</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Silva, Ht" uniqKey="Silva H">HT Silva</name></author><author><name sortKey="Yang, Hc" uniqKey="Yang H">HC Yang</name></author><author><name sortKey="Abouljoud, M" uniqKey="Abouljoud M">M Abouljoud</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kr Mer, Bk" uniqKey="Kr Mer B">BK Krämer</name></author><author><name sortKey="Charpentier, B" uniqKey="Charpentier B">B Charpentier</name></author><author><name sortKey="B Ckman, L" uniqKey="B Ckman L">L Bäckman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ekberg, H" uniqKey="Ekberg H">H Ekberg</name></author><author><name sortKey="Tedesco Silva, H" uniqKey="Tedesco Silva H">H Tedesco-Silva</name></author><author><name sortKey="Demirbas, A" uniqKey="Demirbas A">A Demirbas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vincenti, F" uniqKey="Vincenti F">F Vincenti</name></author><author><name sortKey="Charpentier, B" uniqKey="Charpentier B">B Charpentier</name></author><author><name sortKey="Vanrenterghem, Y" uniqKey="Vanrenterghem Y">Y Vanrenterghem</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Greef, Ke" uniqKey="De Greef K">KE De Greef</name></author><author><name sortKey="Ysebaert, Dk" uniqKey="Ysebaert D">DK Ysebaert</name></author><author><name sortKey="Vercauteren, Sr" uniqKey="Vercauteren S">SR Vercauteren</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Racusen, Lc" uniqKey="Racusen L">LC Racusen</name></author><author><name sortKey="Solez, K" uniqKey="Solez K">K Solez</name></author><author><name sortKey="Colvin, Rb" uniqKey="Colvin R">RB Colvin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rostaing, L" uniqKey="Rostaing L">L Rostaing</name></author><author><name sortKey="Cantarovich, D" uniqKey="Cantarovich D">D Cantarovich</name></author><author><name sortKey="Mourad, G" uniqKey="Mourad G">G Mourad</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vitko, S" uniqKey="Vitko S">S Vítko</name></author><author><name sortKey="Klinger, M" uniqKey="Klinger M">M Klinger</name></author><author><name sortKey="Salmela, K" uniqKey="Salmela K">K Salmela</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vitko, S" uniqKey="Vitko S">S Vítko</name></author><author><name sortKey="Wlodarczyk, Z" uniqKey="Wlodarczyk Z">Z Wlodarczyk</name></author><author><name sortKey="Kyllonen, L" uniqKey="Kyllonen L">L Kyllönen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rosengard, Br" uniqKey="Rosengard B">BR Rosengard</name></author><author><name sortKey="Feng, S" uniqKey="Feng S">S Feng</name></author><author><name sortKey="Alfrey, Ej" uniqKey="Alfrey E">EJ Alfrey</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Transplantation</journal-id><journal-id journal-id-type="iso-abbrev">Transplantation</journal-id><journal-id journal-id-type="publisher-id">TP</journal-id><journal-title-group><journal-title>Transplantation</journal-title></journal-title-group><issn pub-type="ppub">0041-1337</issn><issn pub-type="epub">1534-6080</issn><publisher><publisher-name>Lippincott Williams & Wilkins</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23982340</article-id><article-id pub-id-type="pmc">3864174</article-id><article-id pub-id-type="publisher-id">TP203287</article-id><article-id pub-id-type="doi">10.1097/TP.0b013e3182a203bd</article-id><article-id pub-id-type="art-access-id">00010</article-id><article-categories><subj-group subj-group-type="heading"><subject>Clinical and Translational Research</subject></subj-group></article-categories><title-group><article-title>OSAKA Trial: A Randomized, Controlled Trial Comparing Tacrolimus QD and BD in Kidney Transplantation</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Albano</surname><given-names>Laetitia</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Banas</surname><given-names>Bernhard</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Klempnauer</surname><given-names>Juergen L.</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Glyda</surname><given-names>Maciej</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Viklicky</surname><given-names>Ondrej</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kamar</surname><given-names>Nassim</given-names></name><xref ref-type="aff" rid="aff6 aff7"><sup>6,7</sup></xref></contrib><contrib contrib-type="author"><collab>on behalf of the Optimising immunoSuppression After Kidney transplantation with ADVAGRAF (OSAKA) study group</collab></contrib></contrib-group><aff id="aff1"><sup>1</sup> Department of Nephrology, Centre Hospitalier Universitaire de Nice, Nice, France.</aff><aff id="aff2"><sup>2</sup> Internal Medicine II-Nephrology, University Medical Center, Regensburg, Germany.</aff><aff id="aff3"><sup>3</sup> General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany.</aff><aff id="aff4"><sup>4</sup> Department of Transplantology and Surgery, District Public Hospital, Poznan, Poland.</aff><aff id="aff5"><sup>5</sup> Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.</aff><aff id="aff6"><sup>6</sup> Department of Nephrology, Dialysis and Organ Transplantation, Toulouse University Hospital, Toulouse, France.</aff><aff id="aff7"><sup>7</sup> Address correspondence to: Nassim Kamar, M.D., Department of Nephrology, Dialysis and Organ Transplantation, Toulouse University Hospital, CHU Rangueil TSA 50032, 31059 Toulouse Cedex 9, France.</aff><pub-date pub-type="ppub"><day>27</day><month>11</month><year>2013</year></pub-date><pub-date pub-type="epub"><day>19</day><month>11</month><year>2013</year></pub-date><volume>96</volume><issue>10</issue><fpage>897</fpage><lpage>903</lpage><history><date date-type="accepted"><day>27</day><month>8</month><year>2013</year></date></history><permissions><copyright-statement>Copyright © 2013 by Lippincott Williams & Wilkins</copyright-statement><copyright-year>2013</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-nd/3.0"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.</license-p></license></permissions><self-uri xlink:type="simple" xlink:href="tp-96-897.pdf"></self-uri><abstract><sec><title>Background</title><p>The once-daily (QD), prolonged-release formulation of tacrolimus has been shown to improve adherence versus twice-daily (BD) tacrolimus. Treatment nonadherence in transplant recipients has been associated with poor graft outcomes.</p></sec><sec><title>Methods</title><p>This open-label, parallel-group study randomized adults with end-stage renal disease undergoing primary kidney transplantation or retransplantation to an initial dose of tacrolimus BD 0.2 mg/kg per day (Arm 1; n=309), QD 0.2 mg/kg per day (Arm 2; n=302), QD 0.3 mg/kg per day (Arm 3; n=304) all with mycophenolate mofetil and corticosteroids (tapered) over 24 weeks, or tacrolimus QD 0.2 mg/kg per day with mycophenolate mofetil, basiliximab, and corticosteroids given only perioperatively (Arm 4; n=283). The primary composite endpoint (efficacy failure; per protocol set) was defined as graft loss, biopsy-confirmed acute rejection, or graft dysfunction at week 24. Graft dysfunction was defined as estimated glomerular filtration rate Modification of Diet in Renal Disease-4 formula of less than 40 mL/min/1.73 m<sup>2</sup>. The prespecified noninferiority margin was 12.5%.</p></sec><sec><title>Results</title><p>The per protocol set included 976 patients: 237, 263, 246, and 230 patients in Arms 1 to 4, respectively. Noninferiority of the composite endpoint was demonstrated for Arm 2 versus Arm 1; Kaplan–Meier estimates of efficacy failure were 42.2% and 40.6%, respectively (difference, −1.6%; 95% confidence interval [CI], −12.2% to 9.0%). Noninferiority to Arm 1 was not confirmed for Arm 3 (difference, −3.5%; 95% CI, −13.6% to 6.6%) or Arm 4 (difference, −7.1%; 95% CI, −16.1% to 1.9%). Graft dysfunction (estimated glomerular filtration rate <40 mL/min/1.73 m<sup>2</sup>) was the main determinant of composite-endpoint efficacy failure across all arms.</p></sec><sec><title>Conclusions</title><p>In patients representative of the European kidney transplant population, tacrolimus QD-based immunosuppression (0.2 mg/kg/day), without induction, showed similar efficacy to 0.2 mg/kg per day tacrolimus BD.</p></sec></abstract><abstract abstract-type="toc"><p>Supplemental digital content is available in the article.</p></abstract><kwd-group><title>Keywords</title><kwd>Tacrolimus</kwd><kwd>Kidney transplantation</kwd><kwd>Extended-criteria donor</kwd><kwd>Composite endpoint for graft failure</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>OPEN-ACCESS</meta-name><meta-value>TRUE</meta-value></custom-meta><custom-meta><meta-name>SDC</meta-name><meta-value>T</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc><affiliations><list><country><li>Allemagne</li><li>France</li><li>Pologne</li><li>République tchèque</li></country><region><li>Basse-Saxe</li><li>Bohême centrale</li></region><settlement><li>Hanovre</li><li>Nice</li><li>Prague</li></settlement></list><tree><noCountry><name sortKey="Kamar, Nassim" sort="Kamar, Nassim" uniqKey="Kamar N" first="Nassim" last="Kamar">Nassim Kamar</name></noCountry><country name="France"><noRegion><name sortKey="Albano, Laetitia" sort="Albano, Laetitia" uniqKey="Albano L" first="Laetitia" last="Albano">Laetitia Albano</name></noRegion></country><country name="Allemagne"><noRegion><name sortKey="Banas, Bernhard" sort="Banas, Bernhard" uniqKey="Banas B" first="Bernhard" last="Banas">Bernhard Banas</name></noRegion><name sortKey="Klempnauer, Juergen L" sort="Klempnauer, Juergen L" uniqKey="Klempnauer J" first="Juergen L." last="Klempnauer">Juergen L. Klempnauer</name></country><country name="Pologne"><noRegion><name sortKey="Glyda, Maciej" sort="Glyda, Maciej" uniqKey="Glyda M" first="Maciej" last="Glyda">Maciej Glyda</name></noRegion></country><country name="République tchèque"><region name="Bohême centrale"><name sortKey="Viklicky, Ondrej" sort="Viklicky, Ondrej" uniqKey="Viklicky O" first="Ondrej" last="Viklicky">Ondrej Viklicky</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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