{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T23:26:09Z","timestamp":1793921169164,"version":"4.8.0"},"reference-count":37,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2025,7,22]]},"abstract":"\n Importance<\/jats:title>\n Guidelines recommend augmenting enteral protein during critical illness, but the impact on patient outcomes is uncertain.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To determine whether augmenting enteral protein increases days alive and free from hospitalization.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This cluster randomized, crossover, open-label trial recruited critically ill patients receiving enteral nutrition from 8 intensive care units (ICUs) in Australia and New Zealand from May 23, 2022, to August 23, 2023, with final follow-up on November 21, 2023.<\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n Two isocaloric enteral formulae were compared: augmented protein (100 g protein\/L) vs usual protein (63 g protein\/L). ICUs used formulae sequentially for 3 months over a 12-month period; 4 ICUs commenced with augmented protein and 4 commenced with usual protein.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was the number of days free of admittance to the index hospital and alive at day 90. Secondary outcomes included days free of the index hospital at day 90 in survivors; alive at day 90; durations of invasive ventilation, ICU, and hospital admission; incidences of tracheostomy insertion and new kidney replacement therapy; and hospital discharge destination.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 3397 patients were included (median [IQR] age, 61 (48-71) years; 2157 [64%] male). The median (IQR) number of days free of the index hospital and alive at day 90 was 62 (0-77) days in the augmented protein group and 64 (0-77) days in the usual protein group, with an adjusted-for-period between-group median difference of \u22121.97 (95% CI, \u22127.24 to 3.30) days (\n P<\/jats:italic>\n \u2009=\u2009.46). At day 90, a total of 1221 of 1681 patients (72.6%) were alive in the augmented protein group and 1269 of 1716 (74.0%) were alive in the usual protein group (risk ratio, 0.99 [95% CI, 0.95-1.03]). Between-group differences for secondary outcomes included the following: difference in median days free of hospital in survivors, 0.01 (95% CI, \u22121.94 to 1.96) days; difference in mean duration of invasive ventilation, 6.8 (95% CI, \u22123.0 to 16.5) hours; cause-specific hazard ratios for durations of ICU admission (time to live ICU discharge), 0.93 (95% CI, 0.88-1.00) and hospital admission (time to live hospital discharge), 0.96 (95% CI, 0.90-1.02); and risk ratio for tracheostomy, 1.15 (95% CI, 0.66-2.01) and new kidney replacement therapy, 0.97 (95% CI, 0.81-1.16). Discharge destinations were similar.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n Augmenting enteral protein during critical illness did not improve number of days free of the index hospital and alive at day 90.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ANZCTR Identifier:\n ACTRN12621001484831<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jama.2025.9110","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T04:30:16Z","timestamp":1749616216000},"page":"319","source":"Crossref","is-referenced-by-count":72,"title":["Augmented Enteral Protein During Critical Illness"],"prefix":"10.1001","volume":"334","author":[{"given":"Matthew J.","family":"Summers","sequence":"first","affiliation":[{"name":"Discipline of Acute Care Medicine, The University of Adelaide, Adelaide, South Australia, Australia"},{"name":"Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee-anne S.","family":"Chapple","sequence":"additional","affiliation":[{"name":"Discipline of Acute Care Medicine, The University of Adelaide, Adelaide, South Australia, Australia"},{"name":"Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia"},{"name":"Centre for Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, South Australia, Australia"},{"name":"Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Karahalios","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Methods and Implementation Support for Clinical and Health research (MISCH) Hub, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rinaldo","family":"Bellomo","sequence":"additional","affiliation":[{"name":"Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia"},{"name":"Intensive Care Unit, Austin Health, Heidelberg, Victoria, Australia"},{"name":"Department of Critical Care, The University of Melbourne, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne J.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Discipline of Acute Care Medicine, The University of Adelaide, Adelaide, South Australia, Australia"},{"name":"Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia"},{"name":"Centre for Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, South Australia, Australia"},{"name":"Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzie","family":"Ferrie","sequence":"additional","affiliation":[{"name":"Department of Nutrition & Dietetics, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia"},{"name":"Faculty of Medicine and Health, University of Sydney, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Finnis","sequence":"additional","affiliation":[{"name":"Discipline of Acute Care Medicine, The University of Adelaide, Adelaide, South Australia, Australia"},{"name":"Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia"},{"name":"Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia"},{"name":"Department of Critical Care, The University of Melbourne, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"French","sequence":"additional","affiliation":[{"name":"Department of Critical Care, The University of Melbourne, Melbourne, Australia"},{"name":"Intensive Care Unit, Sunshine Hospital, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Hurford","sequence":"additional","affiliation":[{"name":"Medical Research Institute of New Zealand, Wellington, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nima","family":"Kakho","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, University Hospital Geelong, Geelong, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Maiden","sequence":"additional","affiliation":[{"name":"Department of Critical Care, The University of Melbourne, Melbourne, Australia"},{"name":"Intensive Care Unit, University Hospital Geelong, Geelong, Victoria, Australia"},{"name":"Intensive Care Unit, Royal Melbourne Hospital, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie N.","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"Discipline of Acute Care Medicine, The University of Adelaide, Adelaide, South Australia, Australia"},{"name":"Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra L.","family":"Peake","sequence":"additional","affiliation":[{"name":"Discipline of Acute Care Medicine, The University of Adelaide, Adelaide, South Australia, Australia"},{"name":"Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia"},{"name":"Department of Intensive Care Medicine, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey J.","family":"Presneill","sequence":"additional","affiliation":[{"name":"Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia"},{"name":"Department of Critical Care, The University of Melbourne, Melbourne, Australia"},{"name":"Intensive Care Unit, Royal Melbourne Hospital, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma J.","family":"Ridley","sequence":"additional","affiliation":[{"name":"Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia"},{"name":"Dietetics and Nutrition, Alfred Hospital, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Tran-Duy","sequence":"additional","affiliation":[{"name":"Methods and Implementation Support for Clinical and Health research (MISCH) Hub, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia"},{"name":"Centre for Health Policy, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia J.","family":"Williams","sequence":"additional","affiliation":[{"name":"Discipline of Acute Care Medicine, The University of Adelaide, Adelaide, South Australia, Australia"},{"name":"Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia"},{"name":"Department of Intensive Care Medicine, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Critical Care, The University of Melbourne, Melbourne, Australia"},{"name":"Intensive Care Unit, Sunshine Hospital, Melbourne, Victoria, Australia"},{"name":"Intensive Care Unit, Wellington Hospital, Wellington, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Zaloumis","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Methods and Implementation Support for Clinical and Health research (MISCH) Hub, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M.","family":"Deane","sequence":"additional","affiliation":[{"name":"Department of Critical Care, The University of Melbourne, Melbourne, Australia"},{"name":"Intensive Care Unit, Royal Melbourne Hospital, Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzie","family":"Ferrie","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imogen","family":"Asser","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nerissa","family":"Brown","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee-anne","family":"Chapple","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Doherty","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Finnis","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahni","family":"Foster","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Glasby","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhea","family":"Louis","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"McDonald","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Plummer","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Rivett","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Summers","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Peake","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Kurenda","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srilatha","family":"Vemparala","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Williams","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rinaldo","family":"Bellomo","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Choong","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn","family":"Eastwood","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Hamilton","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Peck","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Young","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Barge","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Barrese","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Byrne","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Deane","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Fetterplace","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Gigli","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Maiden","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Presneill","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna","family":"Tascone","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kym","family":"Wittholz","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Bates","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"French","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haindavi","family":"Muppa","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giang","family":"Nguyen","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Schembri","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey","family":"Hawker","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Horton","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda","family":"Jaques","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nima","family":"Kakho","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jemma","family":"Trickey","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April","family":"Aguilar","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Butt","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Rose","family":"Sol Cruz","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsha","family":"Delaney","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dushanka","family":"Hettige","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Hurford","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reece","family":"Latonio","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eden","family":"Lesona","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joradee","family":"Marmol","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leanlove","family":"Navarra","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Qiu","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nola","family":"Wood-Harris","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Young","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Karahalios","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Zaloumis","sequence":"additional","affiliation":[{"name":"for the TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"1","key":"joi250040r1","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1177\/0148607115583675","article-title":"Clinical outcomes related to protein delivery in a critically ill population: a multicenter, multinational observation study.","volume":"40","author":"Nicolo","year":"2016","journal-title":"JPEN J Parenter Enteral Nutr"},{"issue":"1","key":"joi250040r2","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1002\/jpen.2267","article-title":"Guidelines for the provision of nutrition support therapy in the adult critically ill patient: the American Society for Parenteral and Enteral Nutrition.","volume":"46","author":"Compher","year":"2022","journal-title":"JPEN J Parenter Enteral Nutr"},{"issue":"1","key":"joi250040r3","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.clnu.2018.08.037","article-title":"ESPEN guideline on clinical nutrition in the intensive care unit.","volume":"38","author":"Singer","year":"2019","journal-title":"Clin Nutr"},{"issue":"9","key":"joi250040r4","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1016\/j.clnu.2023.07.011","article-title":"ESPEN practical and partially revised guideline: Clinical nutrition in the intensive care unit.","volume":"42","author":"Singer","year":"2023","journal-title":"Clin Nutr"},{"issue":"8","key":"joi250040r5","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1002\/jpen.1163","article-title":"Nutrition therapy in Australia and New Zealand intensive care units: an international comparison study.","volume":"42","author":"Ridley","year":"2018","journal-title":"JPEN J Parenter Enteral Nutr"},{"issue":"4","key":"joi250040r6","doi-asserted-by":"publisher","first-page":"386","DOI":"10.51893\/2021.4.OA3","article-title":"Protein delivery in mechanically ventilated adults in Australia and New Zealand: current practice.","volume":"23","author":"Murthy","year":"2023","journal-title":"Crit Care Resusc"},{"issue":"935","key":"joi250040r7","first-page":"1","article-title":"Protein and amino acid requirements in human nutrition.","author":"Joint WHO\/FAO\/UNU Expert Consultation","year":"2007","journal-title":"World Health Organ Tech Rep Ser"},{"issue":"10376","key":"joi250040r8","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1016\/S0140-6736(22)02469-2","article-title":"The effect of higher protein dosing in critically ill patients with high nutritional risk (EFFORT Protein).","volume":"401","author":"Heyland","year":"2023","journal-title":"Lancet"},{"issue":"10453","key":"joi250040r9","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/S0140-6736(24)01304-7","article-title":"Effect of high versus standard protein provision on functional recovery in people with critical illness (PRECISe).","volume":"404","author":"Bels","year":"2024","journal-title":"Lancet"},{"issue":"1","key":"joi250040r10","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s13054-023-04783-1","article-title":"The effects of higher versus lower protein delivery in critically ill patients: an updated systematic review and meta-analysis of randomized controlled trials with trial sequential analysis.","volume":"28","author":"Lee","year":"2024","journal-title":"Crit Care"},{"issue":"4","key":"joi250040r11","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1002\/jpen.2059","article-title":"Use of a high-protein enteral nutrition formula to increase protein delivery to critically ill patients: a randomized, blinded, parallel-group, feasibility trial.","volume":"45","author":"Chapple","year":"2021","journal-title":"JPEN J Parenter Enteral Nutr"},{"issue":"3","key":"joi250040r12","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.ccrj.2023.08.001","article-title":"Study protocol for TARGET protein: the effect of augmented administration of enteral protein to critically ill adults on clinical outcomes: a cluster randomised, cross-sectional, double cross-over, clinical trial.","volume":"25","author":"Summers","year":"2023","journal-title":"Crit Care Resusc"},{"issue":"1","key":"joi250040r13","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s13063-025-08759-0","article-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.","volume":"26","author":"Zaloumis","year":"2025","journal-title":"Trials"},{"key":"joi250040r14","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2024-080472","article-title":"Reporting of cluster randomised crossover trials: extension of the CONSORT 2010 statement with explanation and elaboration.","volume":"388","author":"McKenzie","year":"2025","journal-title":"BMJ"},{"issue":"32","key":"joi250040r16","doi-asserted-by":"publisher","first-page":"E901","DOI":"10.1503\/cmaj.200077","article-title":"Development of the Instrument to assess the Credibility of Effect Modification Analyses (ICEMAN) in randomized controlled trials and meta-analyses.","volume":"192","author":"Schandelmaier","year":"2020","journal-title":"CMAJ"},{"issue":"19","key":"joi250040r17","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1056\/NEJMoa1811687","article-title":"Energy-dense versus routine enteral nutrition in the critically ill.","volume":"379","author":"Chapman","year":"2018","journal-title":"N Engl J Med"},{"issue":"1","key":"joi250040r18","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s40488-017-0073-4","article-title":"Quantile regression for overdispersed count data: a hierarchical method.","volume":"4","author":"Congdon","year":"2017","journal-title":"J Stat Distrib Appl"},{"issue":"1","key":"joi250040r19","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1186\/s13054-023-04663-8","article-title":"The impact of higher protein dosing on outcomes in critically ill patients with acute kidney injury: a post hoc analysis of the EFFORT protein trial.","volume":"27","author":"Stoppe","year":"2023","journal-title":"Crit Care"},{"issue":"6","key":"joi250040r20","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1164\/rccm.202112-2780OC","article-title":"Muscle protein synthesis after protein administration in critical illness.","volume":"206","author":"Chapple","year":"2022","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"joi250040r21","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s13054-024-04799-1","article-title":"Association between urea trajectory and protein dose in critically ill adults: a secondary exploratory analysis of the effort protein trial (RE-EFFORT).","volume":"28","author":"Haines","year":"2024","journal-title":"Crit Care"},{"issue":"2","key":"joi250040r22","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1097\/MCO.0000000000000992","article-title":"Urea cycle disorders in critically Ill adults.","volume":"27","author":"Long","year":"2024","journal-title":"Curr Opin Clin Nutr Metab Care"},{"issue":"2","key":"joi250040r23","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1097\/MCO.0000000000001016","article-title":"Editorial: the interaction between protein delivery and blood urea and ammonia during critical illness.","volume":"27","author":"Deane","year":"2024","journal-title":"Curr Opin Clin Nutr Metab Care"},{"issue":"4","key":"joi250040r24","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1097\/MCC.0000000000001056","article-title":"Nutrition and autophagy deficiency in critical illness.","volume":"29","author":"Vanhorebeek","year":"2023","journal-title":"Curr Opin Crit Care"},{"issue":"8","key":"joi250040r25","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/S2213-2600(13)70183-8","article-title":"Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: a subanalysis of the EPaNIC trial.","volume":"1","author":"Hermans","year":"2013","journal-title":"Lancet Respir Med"},{"issue":"11","key":"joi250040r26","doi-asserted-by":"publisher","first-page":"2459","DOI":"10.1177\/09622802211037073","article-title":"Sample sizes for cluster-randomised trials with continuous outcomes: accounting for uncertainty in a single intra-cluster correlation estimate.","volume":"30","author":"Lewis","year":"2021","journal-title":"Stat Methods Med Res"},{"issue":"1","key":"joi250040r27","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1186\/s13063-017-2113-2","article-title":"Understanding the cluster randomised crossover design.","volume":"18","author":"Arnup","year":"2017","journal-title":"Trials"},{"issue":"1","key":"joi250040r28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jeph.2024.202195","article-title":"What type of cluster randomized trial for which setting?","volume":"72","author":"Hemming","year":"2024","journal-title":"J Epidemiol Popul Health"},{"issue":"1","key":"joi250040r29","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1186\/s13063-023-07507-6","article-title":"Replacing protein via enteral nutrition in a stepwise approach in critically ill patients: the REPLENISH randomized clinical trial protocol.","volume":"24","author":"Arabi","year":"2023","journal-title":"Trials"},{"issue":"7","key":"joi250040r30","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1016\/S2213-2600(23)00092-9","article-title":"Low versus standard calorie and protein feeding in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3).","volume":"11","author":"Reignier","year":"2023","journal-title":"Lancet Respir Med"},{"issue":"4","key":"joi250040r31","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1111\/anae.15644","article-title":"Hospital re-admission after critical care survival: a systematic review and meta-analysis.","volume":"77","author":"McPeake","year":"2022","journal-title":"Anaesthesia"},{"key":"joi250040r32","doi-asserted-by":"publisher","DOI":"10.62675\/2965-2774.20240088-en","article-title":"Challenges and limitations of using ventilator-free days as an outcome in critical care trials.","volume":"36","author":"Bruhn","year":"2024","journal-title":"Crit Care Sci"},{"issue":"8","key":"joi250040r33","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-015828","article-title":"Validation of days at home as an outcome measure after surgery: a prospective cohort study in Australia.","volume":"7","author":"Myles","year":"2017","journal-title":"BMJ Open"},{"issue":"12","key":"joi250040r34","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCOUTCOMES.118.004755","article-title":"Days alive and out of hospital: exploring a patient-centered, pragmatic outcome in a clinical trial of patients with acute coronary syndromes.","volume":"11","author":"Fanaroff","year":"2018","journal-title":"Circ Cardiovasc Qual Outcomes"},{"key":"joi250040r35","doi-asserted-by":"publisher","DOI":"10.62675\/2965-2774.20240246-en","article-title":"Alternative approaches to analyzing ventilator-free days, mortality and duration of ventilation in critical care research.","volume":"36","author":"Serpa Neto","year":"2024","journal-title":"Crit Care Sci"},{"issue":"1","key":"joi250040r36","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1186\/s12874-023-01963-z","article-title":"Use of days alive without life support and similar count outcomes in randomised clinical trials.","volume":"23","author":"Granholm","year":"2023","journal-title":"BMC Med Res Methodol"},{"issue":"7","key":"joi250040r37","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1001\/jama.2019.22190","article-title":"Effect of stress ulcer prophylaxis with proton pump inhibitors vs histamine-2 receptor blockers on in-hospital mortality among ICU patients receiving invasive mechanical ventilation: the PEPTIC randomized clinical trial.","volume":"323","author":"Young","year":"2020","journal-title":"JAMA"},{"key":"joi250040r15","unstructured":"The Australian Institute of Health and Welfare. National death index. Updated May 8, 2024. Accessed October 2, 2024. https:\/\/www.aihw.gov.au\/about-our-data\/our-data-collections\/national-death-index"}],"container-title":["JAMA"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jama\/articlepdf\/2835302\/jama_summers_2025_oi_250040_1753124024.36498.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T15:00:43Z","timestamp":1753196443000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jama\/fullarticle\/2835302"}},"subtitle":["The TARGET Protein Randomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2025,7,22]]},"references-count":37,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,7,22]]}},"URL":"https:\/\/doi.org\/10.1001\/jama.2025.9110","relation":{},"ISSN":["0098-7484"],"issn-type":[{"value":"0098-7484","type":"print"}],"subject":[],"published":{"date-parts":[[2025,7,22]]}}}