Detailed statistical analysis plan for ALBINO: effect of Allopurinol in addition to hypothermia for hypoxic-ischemic Brain Injury on Neurocognitive Outcome — a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III)

  1. Engel, Corinna ORCID logo
  2. Rüdiger, Mario
  3. Benders, Manon J. N. L.
  4. van Bel, Frank
  5. Allegaert, Karel
  6. Naulaers, Gunnar
  7. Bassler, Dirk
  8. Klebermaß-Schrehof, Katrin
  9. Vento, Maximo
  10. Vilan, Ana
  11. Falck, Mari
  12. Mauro, Isabella
  13. Metsäranta, Marjo
  14. Vanhatalo, Sampsa
  15. Mazela, Jan
  16. Metsvaht, Tuuli
  17. van der Vlught, Roselinda
  18. Franz, Axel R.
  19. for the ALBINO Study Group
  20. Poets, Christian F.
  21. Guimarães, Hercilia
  22. Stiri, Tom
  23. Cattarossi, Luigi
  24. van Veldhuizen, Cees K. W.
  25. Maiwald, Christian A.
  26. Bergmann, Iris
  27. Weiss, Monika
  28. Eichhorn, Andreas
  29. Raubuch, Michael
  30. Schuler, Birgit
  31. Laméris, Bas
  32. van Ramshorst, Thirza
  33. Kliniken, Tirol
  34. Brandner, Johannes
  35. Tackoen, Marie
  36. Reibel, Ruth
  37. Ilmoja, Mari-Liis
  38. Saik, Pille
  39. Käär, Ruth
  40. Andresson, Pille
  41. der J. W. Goethe, Klinikum
  42. Schloesser, Main Rolf
  43. Carus, Carl Gustav
  44. Winkler, Stefan
  45. Hoehn, Thomas
  46. Teig, Norbert
  47. Schroth, Michael
  48. Fusch, Christoph
  49. Thome, Ulrich H.
  50. Ehrhardt, Harald
  51. Carnielli, Ancona Virgilio
  52. Napolitano, Marcello
  53. Faldini, Francesca
  54. “V.Buzzi”, Bambini
  55. Lista, Milano Gianluca
  56. Barbarini, Mario
  57. Pagani, Laura
  58. Mastretta, Emmanuele
  59. Vento, Giovanni
  60. Fumagalli, Monica
  61. van Weissenbruch, Mirjam M.
  62. van Straaten, Henrica L. M.
  63. Annink, Kim V.
  64. Dudink, Jeroen
  65. Derks, Jan B.
  66. de Boer, Inge P.
  67. Meijssen, Clemens B.
  68. de Haan, Timo R.
  69. van Rooij, Linda G.
  70. van Hillegersberg, Jacqueline L.
  71. van Dongen, Minouche
  72. Dijkman, Koen P.
  73. van Houten, Marlies A.
  74. van der Schoor, Sophie R. D.
  75. Schneider, Moritz
  76. Nestaas, Eirik
  77. Nakstad, Britt
  78. Karpinski, Lukas
  79. Gulczynska, Ewa
  80. Ferraz, Claudia
  81. Pereira, Almerinda
  82. Barroso, Rosalina
  83. da Graça, Mendes
  84. Tomé, Teresa
  85. Pinto, Filomena
  86. Rodilla, Juan Martínez
  87. Pico, Maria Luz.Couce
  88. Suazo, José Antonio Hurtado
  89. Valverde, Eva
  90. Lorenzo, José Ramón Fernández
  91. Boix, Héctor
  92. Parrilla, Francisco Jimenez
  93. Blanco, Dorotea
  94. Loureiro, Begoña
  95. Moral-Pumarega, Maria Teresa
  96. Maletzki, Julia
  97. Knoepfli, Claudia
  98. Hagmann, Cornelia
  99. Kleber, Michael
  100. Stocker, Martin
  101. Riedel, Thomas

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1000 Titel
  • Detailed statistical analysis plan for ALBINO: effect of Allopurinol in addition to hypothermia for hypoxic-ischemic Brain Injury on Neurocognitive Outcome — a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III)
1000 Autor/in
  1. Engel, Corinna |
  2. Rüdiger, Mario |
  3. Benders, Manon J. N. L. |
  4. van Bel, Frank |
  5. Allegaert, Karel |
  6. Naulaers, Gunnar |
  7. Bassler, Dirk |
  8. Klebermaß-Schrehof, Katrin |
  9. Vento, Maximo |
  10. Vilan, Ana |
  11. Falck, Mari |
  12. Mauro, Isabella |
  13. Metsäranta, Marjo |
  14. Vanhatalo, Sampsa |
  15. Mazela, Jan |
  16. Metsvaht, Tuuli |
  17. van der Vlught, Roselinda |
  18. Franz, Axel R. |
  19. for the ALBINO Study Group |
  20. Poets, Christian F. |
  21. Guimarães, Hercilia |
  22. Stiri, Tom |
  23. Cattarossi, Luigi |
  24. van Veldhuizen, Cees K. W. |
  25. Maiwald, Christian A. |
  26. Bergmann, Iris |
  27. Weiss, Monika |
  28. Eichhorn, Andreas |
  29. Raubuch, Michael |
  30. Schuler, Birgit |
  31. Laméris, Bas |
  32. van Ramshorst, Thirza |
  33. Kliniken, Tirol |
  34. Brandner, Johannes |
  35. Tackoen, Marie |
  36. Reibel, Ruth |
  37. Ilmoja, Mari-Liis |
  38. Saik, Pille |
  39. Käär, Ruth |
  40. Andresson, Pille |
  41. der J. W. Goethe, Klinikum |
  42. Schloesser, Main Rolf |
  43. Carus, Carl Gustav |
  44. Winkler, Stefan |
  45. Hoehn, Thomas |
  46. Teig, Norbert |
  47. Schroth, Michael |
  48. Fusch, Christoph |
  49. Thome, Ulrich H. |
  50. Ehrhardt, Harald |
  51. Carnielli, Ancona Virgilio |
  52. Napolitano, Marcello |
  53. Faldini, Francesca |
  54. “V.Buzzi”, Bambini |
  55. Lista, Milano Gianluca |
  56. Barbarini, Mario |
  57. Pagani, Laura |
  58. Mastretta, Emmanuele |
  59. Vento, Giovanni |
  60. Fumagalli, Monica |
  61. van Weissenbruch, Mirjam M. |
  62. van Straaten, Henrica L. M. |
  63. Annink, Kim V. |
  64. Dudink, Jeroen |
  65. Derks, Jan B. |
  66. de Boer, Inge P. |
  67. Meijssen, Clemens B. |
  68. de Haan, Timo R. |
  69. van Rooij, Linda G. |
  70. van Hillegersberg, Jacqueline L. |
  71. van Dongen, Minouche |
  72. Dijkman, Koen P. |
  73. van Houten, Marlies A. |
  74. van der Schoor, Sophie R. D. |
  75. Schneider, Moritz |
  76. Nestaas, Eirik |
  77. Nakstad, Britt |
  78. Karpinski, Lukas |
  79. Gulczynska, Ewa |
  80. Ferraz, Claudia |
  81. Pereira, Almerinda |
  82. Barroso, Rosalina |
  83. da Graça, Mendes |
  84. Tomé, Teresa |
  85. Pinto, Filomena |
  86. Rodilla, Juan Martínez |
  87. Pico, Maria Luz.Couce |
  88. Suazo, José Antonio Hurtado |
  89. Valverde, Eva |
  90. Lorenzo, José Ramón Fernández |
  91. Boix, Héctor |
  92. Parrilla, Francisco Jimenez |
  93. Blanco, Dorotea |
  94. Loureiro, Begoña |
  95. Moral-Pumarega, Maria Teresa |
  96. Maletzki, Julia |
  97. Knoepfli, Claudia |
  98. Hagmann, Cornelia |
  99. Kleber, Michael |
  100. Stocker, Martin |
  101. Riedel, Thomas |
1000 Verlag BioMed Central
1000 Erscheinungsjahr 2024
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2024-01-24
1000 Erschienen in
1000 Quellenangabe
  • 25(1):81
1000 Copyrightjahr
  • 2024
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1186/s13063-023-07828-6 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10809613/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Despite therapeutic hypothermia (TH) and neonatal intensive care, 45–50% of children affected by moderate-to-severe neonatal hypoxic-ischemic encephalopathy (HIE) die or suffer from long-term neurodevelopmental impairment. Additional neuroprotective therapies are sought, besides TH, to further improve the outcome of affected infants.</jats:p> <jats:p>Allopurinol — a xanthine oxidase inhibitor — reduced the production of oxygen radicals and subsequent brain damage in pre-clinical and preliminary human studies of cerebral ischemia and reperfusion, if administered before or early after the insult.</jats:p> <jats:p>This ALBINO trial aims to evaluate the efficacy and safety of allopurinol administered immediately after birth to (near-)term infants with early signs of HIE.</jats:p> </jats:sec><jats:sec> <jats:title>Methods/design</jats:title> <jats:p>The ALBINO trial is an investigator-initiated, randomized, placebo-controlled, double-blinded, multi-national parallel group comparison for superiority investigating the effect of allopurinol in (near-)term infants with neonatal HIE.</jats:p> <jats:p>Primary endpoint is long-term outcome determined as survival with neurodevelopmental impairment versus death versus non-impaired survival at 2 years.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>The primary analysis with three mutually exclusive responses (healthy, death, composite outcome for impairment) will be on the intention-to-treat (ITT) population by a generalized logits model according to Bishop, Fienberg, Holland (Bishop YF, Discrete Multivariate Analysis: Therory and Practice, 1975) and .”will be stratified for the two treatment groups.</jats:p> </jats:sec><jats:sec> <jats:title>Discussion</jats:title> <jats:p>The statistical analysis for the ALBINO study was defined in detail in the study protocol and implemented in this statistical analysis plan published prior to any data analysis. This is in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines.</jats:p> </jats:sec><jats:sec> <jats:title>Trial registration</jats:title> <jats:p>ClinicalTrials.gov NCT03162653. Registered on 22 May 2017.</jats:p> </jats:sec>
1000 Sacherschließung
lokal Infant, Newborn [MeSH]
lokal Hypoxia-Ischemia, Brain/therapy [MeSH]
lokal Hypoxic-ischemic encephalopathy
lokal Control Groups [MeSH]
lokal Perinatal asphyxia
lokal Humans [MeSH]
lokal Brain Injuries [MeSH]
lokal Neonatal oxygen deficiency
lokal Hypothermia, Induced/adverse effects [MeSH]
lokal Infant [MeSH]
lokal Childbirth outcome
lokal Brain injury
lokal Allopurinol/adverse effects [MeSH]
lokal Hypoxia-Ischemia, Brain/diagnosis [MeSH]
lokal Update
lokal Child [MeSH]
lokal Allopurinol
lokal Cerebral palsy
lokal Hypothermia therapy
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
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