TARGET Protein: the effect of augmented administration of enteral protein to critically ill adults on clinical outcomes—statistical analysis plan for a cluster randomized, cross-sectional, double cross-over, clinical trial
Abstract Background The TARGET Protein trial will evaluate the effect of greater enteral protein delivery (augmented protein) on clinical outcomes of critically ill adult patients when compared to usual care. Objective To describe the statistical analysis plan for the TARGET Protein trial. Methods T...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-02-01
|
| Series: | Trials |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13063-025-08759-0 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823861683861323776 |
|---|---|
| author | Sophie Zaloumis Matthew J. Summers Jeffrey J. Presneill Rinaldo Bellomo Lee-anne S. Chapple Marianne J. Chapman Adam M. Deane Suzie Ferrie Craig French Sally Hurford Nima Kakho Matthew J. Maiden Stephanie N. O’Connor Sandra L. Peake Emma J. Ridley An Tran-Duy Patricia J. Williams Paul J. Young Amalia Karahalios on behalf of the TARGET Protein Investigators, the Australian, New Zealand Intensive Care Society Clinical Trials Group |
| author_facet | Sophie Zaloumis Matthew J. Summers Jeffrey J. Presneill Rinaldo Bellomo Lee-anne S. Chapple Marianne J. Chapman Adam M. Deane Suzie Ferrie Craig French Sally Hurford Nima Kakho Matthew J. Maiden Stephanie N. O’Connor Sandra L. Peake Emma J. Ridley An Tran-Duy Patricia J. Williams Paul J. Young Amalia Karahalios on behalf of the TARGET Protein Investigators, the Australian, New Zealand Intensive Care Society Clinical Trials Group |
| author_sort | Sophie Zaloumis |
| collection | DOAJ |
| description | Abstract Background The TARGET Protein trial will evaluate the effect of greater enteral protein delivery (augmented protein) on clinical outcomes of critically ill adult patients when compared to usual care. Objective To describe the statistical analysis plan for the TARGET Protein trial. Methods TARGET Protein is a cluster randomized, cross-sectional, double cross-over, open-label, registry-embedded, pragmatic clinical trial conducted across Australia and New Zealand. The trial randomized eight intensive care units (ICU) to receive enteral formula containing either higher dose enteral protein (augmented protein) or usual dose protein in a 1:1 ratio. Each ICU received one trial formula for a 3-month period and then switched to the alternate formulae. This sequence was repeated, for a total trial length of 12 months. The primary outcome is the number of days free of the index hospital and alive at day 90. Secondary outcomes include proportion of patients alive at day 90, survivor-only analysis of days free of the index hospital at day 90, duration of invasive ventilation, ICU and hospital length of stay, incidence of tracheostomy insertion, renal replacement therapy, and discharge destination. The statistical methods and models which will be used to estimate the effects for the primary and secondary outcomes are described. All statistical models will account for the cluster-randomized cross-over design to ensure correct estimation of the 95% confidence intervals. Trial enrolment is complete with 3412 patients enrolled. Data linkage is ongoing. Conclusion This statistical analysis plan enables transparent reporting of the TARGET Protein trial. It will reduce the risk of potential selective reporting biases. Trial registration Australian New Zealand Clinical Trials Registry (ACTRN12621001484831). Registered on November 1, 2021. |
| format | Article |
| id | doaj-art-e1e711900660491a8cdf929b4eac7efd |
| institution | Kabale University |
| issn | 1745-6215 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj-art-e1e711900660491a8cdf929b4eac7efd2025-02-09T12:53:18ZengBMCTrials1745-62152025-02-0126111010.1186/s13063-025-08759-0TARGET Protein: the effect of augmented administration of enteral protein to critically ill adults on clinical outcomes—statistical analysis plan for a cluster randomized, cross-sectional, double cross-over, clinical trialSophie Zaloumis0Matthew J. Summers1Jeffrey J. Presneill2Rinaldo Bellomo3Lee-anne S. Chapple4Marianne J. Chapman5Adam M. Deane6Suzie Ferrie7Craig French8Sally Hurford9Nima Kakho10Matthew J. Maiden11Stephanie N. O’Connor12Sandra L. Peake13Emma J. Ridley14An Tran-Duy15Patricia J. Williams16Paul J. Young17Amalia Karahalios18on behalf of the TARGET Protein Investigators, the Australian, New Zealand Intensive Care Society Clinical Trials GroupCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, University of MelbourneIntensive Care Unit, Royal Adelaide HospitalAustralian and New Zealand Intensive Care Research Centre, Monash UniversityAustralian and New Zealand Intensive Care Research Centre, Monash UniversityIntensive Care Unit, Royal Adelaide HospitalIntensive Care Unit, Royal Adelaide HospitalDiscipline of Acute Care Medicine, The University of AdelaideDepartment of Nutrition & Dietetics, Royal Prince Alfred HospitalIntensive Care Unit, Sunshine HospitalMedical Research Institute of New ZealandIntensive Care Unit, University Hospital GeelongDepartment of Critical Care, The University of MelbourneIntensive Care Unit, Royal Adelaide HospitalDiscipline of Acute Care Medicine, The University of AdelaideAustralian and New Zealand Intensive Care Research Centre, Monash UniversityMethods and Implementation Support for Clinical and Health (MISCH) Research Hub, Faculty of Medicine, Dentistry, and Health Sciences, University of MelbourneDiscipline of Acute Care Medicine, The University of AdelaideDepartment of Critical Care, The University of MelbourneCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, University of MelbourneAbstract Background The TARGET Protein trial will evaluate the effect of greater enteral protein delivery (augmented protein) on clinical outcomes of critically ill adult patients when compared to usual care. Objective To describe the statistical analysis plan for the TARGET Protein trial. Methods TARGET Protein is a cluster randomized, cross-sectional, double cross-over, open-label, registry-embedded, pragmatic clinical trial conducted across Australia and New Zealand. The trial randomized eight intensive care units (ICU) to receive enteral formula containing either higher dose enteral protein (augmented protein) or usual dose protein in a 1:1 ratio. Each ICU received one trial formula for a 3-month period and then switched to the alternate formulae. This sequence was repeated, for a total trial length of 12 months. The primary outcome is the number of days free of the index hospital and alive at day 90. Secondary outcomes include proportion of patients alive at day 90, survivor-only analysis of days free of the index hospital at day 90, duration of invasive ventilation, ICU and hospital length of stay, incidence of tracheostomy insertion, renal replacement therapy, and discharge destination. The statistical methods and models which will be used to estimate the effects for the primary and secondary outcomes are described. All statistical models will account for the cluster-randomized cross-over design to ensure correct estimation of the 95% confidence intervals. Trial enrolment is complete with 3412 patients enrolled. Data linkage is ongoing. Conclusion This statistical analysis plan enables transparent reporting of the TARGET Protein trial. It will reduce the risk of potential selective reporting biases. Trial registration Australian New Zealand Clinical Trials Registry (ACTRN12621001484831). Registered on November 1, 2021.https://doi.org/10.1186/s13063-025-08759-0Intensive careDietary proteinCluster-randomizedCross-overTrial |
| spellingShingle | Sophie Zaloumis Matthew J. Summers Jeffrey J. Presneill Rinaldo Bellomo Lee-anne S. Chapple Marianne J. Chapman Adam M. Deane Suzie Ferrie Craig French Sally Hurford Nima Kakho Matthew J. Maiden Stephanie N. O’Connor Sandra L. Peake Emma J. Ridley An Tran-Duy Patricia J. Williams Paul J. Young Amalia Karahalios on behalf of the TARGET Protein Investigators, the Australian, New Zealand Intensive Care Society Clinical Trials Group TARGET Protein: the effect of augmented administration of enteral protein to critically ill adults on clinical outcomes—statistical analysis plan for a cluster randomized, cross-sectional, double cross-over, clinical trial Trials Intensive care Dietary protein Cluster-randomized Cross-over Trial |
| title | TARGET Protein: the effect of augmented administration of enteral protein to critically ill adults on clinical outcomes—statistical analysis plan for a cluster randomized, cross-sectional, double cross-over, clinical trial |
| title_full | TARGET Protein: the effect of augmented administration of enteral protein to critically ill adults on clinical outcomes—statistical analysis plan for a cluster randomized, cross-sectional, double cross-over, clinical trial |
| title_fullStr | TARGET Protein: the effect of augmented administration of enteral protein to critically ill adults on clinical outcomes—statistical analysis plan for a cluster randomized, cross-sectional, double cross-over, clinical trial |
| title_full_unstemmed | TARGET Protein: the effect of augmented administration of enteral protein to critically ill adults on clinical outcomes—statistical analysis plan for a cluster randomized, cross-sectional, double cross-over, clinical trial |
| title_short | TARGET Protein: the effect of augmented administration of enteral protein to critically ill adults on clinical outcomes—statistical analysis plan for a cluster randomized, cross-sectional, double cross-over, clinical trial |
| title_sort | target protein the effect of augmented administration of enteral protein to critically ill adults on clinical outcomes statistical analysis plan for a cluster randomized cross sectional double cross over clinical trial |
| topic | Intensive care Dietary protein Cluster-randomized Cross-over Trial |
| url | https://doi.org/10.1186/s13063-025-08759-0 |
| work_keys_str_mv | AT sophiezaloumis targetproteintheeffectofaugmentedadministrationofenteralproteintocriticallyilladultsonclinicaloutcomesstatisticalanalysisplanforaclusterrandomizedcrosssectionaldoublecrossoverclinicaltrial AT matthewjsummers targetproteintheeffectofaugmentedadministrationofenteralproteintocriticallyilladultsonclinicaloutcomesstatisticalanalysisplanforaclusterrandomizedcrosssectionaldoublecrossoverclinicaltrial AT jeffreyjpresneill targetproteintheeffectofaugmentedadministrationofenteralproteintocriticallyilladultsonclinicaloutcomesstatisticalanalysisplanforaclusterrandomizedcrosssectionaldoublecrossoverclinicaltrial AT rinaldobellomo targetproteintheeffectofaugmentedadministrationofenteralproteintocriticallyilladultsonclinicaloutcomesstatisticalanalysisplanforaclusterrandomizedcrosssectionaldoublecrossoverclinicaltrial AT leeanneschapple targetproteintheeffectofaugmentedadministrationofenteralproteintocriticallyilladultsonclinicaloutcomesstatisticalanalysisplanforaclusterrandomizedcrosssectionaldoublecrossoverclinicaltrial AT mariannejchapman targetproteintheeffectofaugmentedadministrationofenteralproteintocriticallyilladultsonclinicaloutcomesstatisticalanalysisplanforaclusterrandomizedcrosssectionaldoublecrossoverclinicaltrial AT adammdeane targetproteintheeffectofaugmentedadministrationofenteralproteintocriticallyilladultsonclinicaloutcomesstatisticalanalysisplanforaclusterrandomizedcrosssectionaldoublecrossoverclinicaltrial AT suzieferrie targetproteintheeffectofaugmentedadministrationofenteralproteintocriticallyilladultsonclinicaloutcomesstatisticalanalysisplanforaclusterrandomizedcrosssectionaldoublecrossoverclinicaltrial AT craigfrench targetproteintheeffectofaugmentedadministrationofenteralproteintocriticallyilladultsonclinicaloutcomesstatisticalanalysisplanforaclusterrandomizedcrosssectionaldoublecrossoverclinicaltrial AT sallyhurford targetproteintheeffectofaugmentedadministrationofenteralproteintocriticallyilladultsonclinicaloutcomesstatisticalanalysisplanforaclusterrandomizedcrosssectionaldoublecrossoverclinicaltrial AT nimakakho targetproteintheeffectofaugmentedadministrationofenteralproteintocriticallyilladultsonclinicaloutcomesstatisticalanalysisplanforaclusterrandomizedcrosssectionaldoublecrossoverclinicaltrial AT matthewjmaiden targetproteintheeffectofaugmentedadministrationofenteralproteintocriticallyilladultsonclinicaloutcomesstatisticalanalysisplanforaclusterrandomizedcrosssectionaldoublecrossoverclinicaltrial AT stephanienoconnor targetproteintheeffectofaugmentedadministrationofenteralproteintocriticallyilladultsonclinicaloutcomesstatisticalanalysisplanforaclusterrandomizedcrosssectionaldoublecrossoverclinicaltrial AT sandralpeake targetproteintheeffectofaugmentedadministrationofenteralproteintocriticallyilladultsonclinicaloutcomesstatisticalanalysisplanforaclusterrandomizedcrosssectionaldoublecrossoverclinicaltrial AT emmajridley targetproteintheeffectofaugmentedadministrationofenteralproteintocriticallyilladultsonclinicaloutcomesstatisticalanalysisplanforaclusterrandomizedcrosssectionaldoublecrossoverclinicaltrial AT antranduy targetproteintheeffectofaugmentedadministrationofenteralproteintocriticallyilladultsonclinicaloutcomesstatisticalanalysisplanforaclusterrandomizedcrosssectionaldoublecrossoverclinicaltrial AT patriciajwilliams targetproteintheeffectofaugmentedadministrationofenteralproteintocriticallyilladultsonclinicaloutcomesstatisticalanalysisplanforaclusterrandomizedcrosssectionaldoublecrossoverclinicaltrial AT pauljyoung targetproteintheeffectofaugmentedadministrationofenteralproteintocriticallyilladultsonclinicaloutcomesstatisticalanalysisplanforaclusterrandomizedcrosssectionaldoublecrossoverclinicaltrial AT amaliakarahalios targetproteintheeffectofaugmentedadministrationofenteralproteintocriticallyilladultsonclinicaloutcomesstatisticalanalysisplanforaclusterrandomizedcrosssectionaldoublecrossoverclinicaltrial AT onbehalfofthetargetproteininvestigatorstheaustraliannewzealandintensivecaresocietyclinicaltrialsgroup targetproteintheeffectofaugmentedadministrationofenteralproteintocriticallyilladultsonclinicaloutcomesstatisticalanalysisplanforaclusterrandomizedcrosssectionaldoublecrossoverclinicaltrial |