Detailed statistical analysis plan for the SafeBoosC III trial: a multinational randomised clinical trial assessing treatment guided by cerebral oxygenation monitoring versus treatment as usual in extremely preterm infants
Abstract Background Infants born extremely preterm are at high risk of dying or suffering from severe brain injuries. Treatment guided by monitoring of cerebral oxygenation may reduce the risk of death and neurologic complications. The SafeBoosC III trial evaluates the effects of treatment guided by...
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| Format: | Article |
| Language: | English |
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BMC
2019-12-01
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| Series: | Trials |
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| Online Access: | https://doi.org/10.1186/s13063-019-3756-y |
| _version_ | 1818589574680543232 |
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| author | Mathias Lühr Hansen Adelina Pellicer Christian Gluud Eugene Dempsey Jonathan Mintzer Simon Hyttel-Sorensen Anne Marie Heuchan Cornelia Hagmann Gabriel Dimitriou Gerhard Pichler Gunnar Naulaers Guoqiang Cheng Ana Vilan Jakub Tkaczyk Karen B. Kreutzer Monica Fumagalli Olivier Claris Siv Fredly Tomasz Szczapa Theis Lange Janus Christian Jakobsen Gorm Greisen |
| author_facet | Mathias Lühr Hansen Adelina Pellicer Christian Gluud Eugene Dempsey Jonathan Mintzer Simon Hyttel-Sorensen Anne Marie Heuchan Cornelia Hagmann Gabriel Dimitriou Gerhard Pichler Gunnar Naulaers Guoqiang Cheng Ana Vilan Jakub Tkaczyk Karen B. Kreutzer Monica Fumagalli Olivier Claris Siv Fredly Tomasz Szczapa Theis Lange Janus Christian Jakobsen Gorm Greisen |
| author_sort | Mathias Lühr Hansen |
| collection | DOAJ |
| description | Abstract Background Infants born extremely preterm are at high risk of dying or suffering from severe brain injuries. Treatment guided by monitoring of cerebral oxygenation may reduce the risk of death and neurologic complications. The SafeBoosC III trial evaluates the effects of treatment guided by cerebral oxygenation monitoring versus treatment as usual. This article describes the detailed statistical analysis plan for the main publication, with the aim to prevent outcome reporting bias and data-driven analyses. Methods/design The SafeBoosC III trial is an investigator-initiated, randomised, multinational, pragmatic phase III trial with a parallel group structure, designed to investigate the benefits and harms of treatment based on cerebral near-infrared spectroscopy monitoring compared with treatment as usual. Randomisation will be 1:1 stratified for neonatal intensive care unit and gestational age (lower gestational age (< 26 weeks) compared to higher gestational age (≥ 26 weeks)). The primary outcome is a composite of death or severe brain injury at 36 weeks postmenstrual age. Primary analysis will be made on the intention-to-treat population for all outcomes, using mixed-model logistic regression adjusting for stratification variables. In the primary analysis, the twin intra-class correlation coefficient will not be considered. However, we will perform sensitivity analyses to address this. Our simulation study suggests that the inclusion of multiple births is unlikely to significantly affect our assessment of intervention effects, and therefore we have chosen the analysis where the twin intra-class correlation coefficient will not be considered as the primary analysis. Discussion In line with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines, we have developed and published this statistical analysis plan for the SafeBoosC III trial, prior to any data analysis. Trial registration ClinicalTrials.org, NCT03770741. Registered on 10 December 2018. |
| first_indexed | 2024-12-16T09:42:49Z |
| format | Article |
| id | doaj.art-c16576035eb44f2e861f809c81efa414 |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-12-16T09:42:49Z |
| publishDate | 2019-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-c16576035eb44f2e861f809c81efa4142022-12-21T22:36:13ZengBMCTrials1745-62152019-12-0120111210.1186/s13063-019-3756-yDetailed statistical analysis plan for the SafeBoosC III trial: a multinational randomised clinical trial assessing treatment guided by cerebral oxygenation monitoring versus treatment as usual in extremely preterm infantsMathias Lühr Hansen0Adelina Pellicer1Christian Gluud2Eugene Dempsey3Jonathan Mintzer4Simon Hyttel-Sorensen5Anne Marie Heuchan6Cornelia Hagmann7Gabriel Dimitriou8Gerhard Pichler9Gunnar Naulaers10Guoqiang Cheng11Ana Vilan12Jakub Tkaczyk13Karen B. Kreutzer14Monica Fumagalli15Olivier Claris16Siv Fredly17Tomasz Szczapa18Theis Lange19Janus Christian Jakobsen20Gorm Greisen21Department of Neonatology, Rigshospitalet, Copenhagen University HospitalDepartment of Neonatology, La Paz University HospitalCopenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University HospitalInfant Centre and Department of Paediatrics and Child Health, University College CorkDivision of Neonatal-Perinatal Medicine, Mountainside Medical CenterDepartment of Neonatology, Rigshospitalet, Copenhagen University HospitalDepartment of Neonatology, Royal Hospital for ChildrenDepartment of Neonatology, Children’s University Hospital of ZürichNICU, Department of Pediatrics, University General Hospital of PatrasDepartment of Pediatrics, Medical University of GrazDepartment of Neonatology, University Hospital LeuvenDepartment of Neonatology, Children’s Hospital of Fudan UniversityDepartment of Neonatology, Centrohospitalar Universitário de São JoãoDepartment of Neonatology, University Hospital MotolDepartment of Neonatology, University Children’s Hospital TuebingenFondazione IRCCS Cà Granda Ospedale Maggiore Policlinico MilanDepartment of Neonatology, Hospices Civil De LyonDepartment of Neonatology, Oslo University HospitalDepartment of Neonatology, Poznan University of Medical SciencesSection of Biostatistics, Department of Publich Health, Copenhagen UniversityCopenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University HospitalDepartment of Neonatology, Rigshospitalet, Copenhagen University HospitalAbstract Background Infants born extremely preterm are at high risk of dying or suffering from severe brain injuries. Treatment guided by monitoring of cerebral oxygenation may reduce the risk of death and neurologic complications. The SafeBoosC III trial evaluates the effects of treatment guided by cerebral oxygenation monitoring versus treatment as usual. This article describes the detailed statistical analysis plan for the main publication, with the aim to prevent outcome reporting bias and data-driven analyses. Methods/design The SafeBoosC III trial is an investigator-initiated, randomised, multinational, pragmatic phase III trial with a parallel group structure, designed to investigate the benefits and harms of treatment based on cerebral near-infrared spectroscopy monitoring compared with treatment as usual. Randomisation will be 1:1 stratified for neonatal intensive care unit and gestational age (lower gestational age (< 26 weeks) compared to higher gestational age (≥ 26 weeks)). The primary outcome is a composite of death or severe brain injury at 36 weeks postmenstrual age. Primary analysis will be made on the intention-to-treat population for all outcomes, using mixed-model logistic regression adjusting for stratification variables. In the primary analysis, the twin intra-class correlation coefficient will not be considered. However, we will perform sensitivity analyses to address this. Our simulation study suggests that the inclusion of multiple births is unlikely to significantly affect our assessment of intervention effects, and therefore we have chosen the analysis where the twin intra-class correlation coefficient will not be considered as the primary analysis. Discussion In line with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines, we have developed and published this statistical analysis plan for the SafeBoosC III trial, prior to any data analysis. Trial registration ClinicalTrials.org, NCT03770741. Registered on 10 December 2018.https://doi.org/10.1186/s13063-019-3756-yRandomised clinical trialExtremely pretermNear-infrared spectroscopyCerebral oximetryStatistical analysis plan |
| spellingShingle | Mathias Lühr Hansen Adelina Pellicer Christian Gluud Eugene Dempsey Jonathan Mintzer Simon Hyttel-Sorensen Anne Marie Heuchan Cornelia Hagmann Gabriel Dimitriou Gerhard Pichler Gunnar Naulaers Guoqiang Cheng Ana Vilan Jakub Tkaczyk Karen B. Kreutzer Monica Fumagalli Olivier Claris Siv Fredly Tomasz Szczapa Theis Lange Janus Christian Jakobsen Gorm Greisen Detailed statistical analysis plan for the SafeBoosC III trial: a multinational randomised clinical trial assessing treatment guided by cerebral oxygenation monitoring versus treatment as usual in extremely preterm infants Trials Randomised clinical trial Extremely preterm Near-infrared spectroscopy Cerebral oximetry Statistical analysis plan |
| title | Detailed statistical analysis plan for the SafeBoosC III trial: a multinational randomised clinical trial assessing treatment guided by cerebral oxygenation monitoring versus treatment as usual in extremely preterm infants |
| title_full | Detailed statistical analysis plan for the SafeBoosC III trial: a multinational randomised clinical trial assessing treatment guided by cerebral oxygenation monitoring versus treatment as usual in extremely preterm infants |
| title_fullStr | Detailed statistical analysis plan for the SafeBoosC III trial: a multinational randomised clinical trial assessing treatment guided by cerebral oxygenation monitoring versus treatment as usual in extremely preterm infants |
| title_full_unstemmed | Detailed statistical analysis plan for the SafeBoosC III trial: a multinational randomised clinical trial assessing treatment guided by cerebral oxygenation monitoring versus treatment as usual in extremely preterm infants |
| title_short | Detailed statistical analysis plan for the SafeBoosC III trial: a multinational randomised clinical trial assessing treatment guided by cerebral oxygenation monitoring versus treatment as usual in extremely preterm infants |
| title_sort | detailed statistical analysis plan for the safeboosc iii trial a multinational randomised clinical trial assessing treatment guided by cerebral oxygenation monitoring versus treatment as usual in extremely preterm infants |
| topic | Randomised clinical trial Extremely preterm Near-infrared spectroscopy Cerebral oximetry Statistical analysis plan |
| url | https://doi.org/10.1186/s13063-019-3756-y |
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