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

Matthew J Summers; Lee-Anne S Chapple; Rinaldo Bellomo; Marianne J Chapman; Suzie Ferrie; Mark E Finnis; Craig French; Sally Hurford; Nima Kakho; Amalia Karahalios; Matthew J Maiden; Stephanie N O'Connor; Sandra L Peake; Jeffrey J Presneill; Emma J Ridley; An Tran-Duy; Patricia J Williams; Paul J Young; Sophie Zaloumis; Adam M Deane; TARGET Protein Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group

doi:10.1016/j.ccrj.2023.08.001

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

Crit Care Resusc. 2023 Sep 29;25(3):147-154. doi: 10.1016/j.ccrj.2023.08.001. eCollection 2023 Sep.

Authors

Matthew J Summers^{1

2}, Lee-Anne S Chapple^{1

2

3

4}, Rinaldo Bellomo^{5

6

4

7}, Marianne J Chapman^{1

2

3

4}, Suzie Ferrie^{8

9}, Mark E Finnis^{1

2

4

7}, Craig French¹⁰, Sally Hurford¹¹, Nima Kakho¹², Amalia Karahalios¹³, Matthew J Maiden^{12

14

7}, Stephanie N O'Connor^{1

2}, Sandra L Peake^{2

4

15}, Jeffrey J Presneill^{4

14

7}, Emma J Ridley^{4

16}, An Tran-Duy¹⁷, Patricia J Williams^{2

4

15}, Paul J Young^{6

11

18}, Sophie Zaloumis¹³, Adam M Deane^{14

7}; TARGET Protein Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group

Affiliations

¹ Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
² Discipline of Acute Care Medicine, The University of Adelaide, Adelaide, South Australia, Australia.
³ National Health and Medical Research Council of Australia, Centre for Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, South Australia, Australia.
⁴ Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia.
⁵ Intensive Care Unit, Austin Health, Heidelberg, Victoria, Australia.
⁶ Department of Critical Care, The University of Melbourne, Melbourne, Victoria, Australia.
⁷ The University of Melbourne, Melbourne Medical School, Department of Medicine and Radiology, Melbourne, Victoria, Australia.
⁸ Department of Nutrition & Dietetics, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
⁹ Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
¹⁰ Intensive Care Unit, Sunshine Hospital, Melbourne, Victoria, Australia.
¹¹ Medical Research Institute of New Zealand, Wellington, New Zealand.
¹² Intensive Care Unit, University Hospital Geelong, Geelong, Victoria, Australia.
¹³ 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.
¹⁴ Intensive Care Unit, Royal Melbourne Hospital, Parkville, Victoria, Australia.
¹⁵ Intensive Care Unit, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia.
¹⁶ Dietetics and Nutrition, Alfred Hospital, Melbourne, Victoria, Australia.
¹⁷ Centre for Health Policy, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
¹⁸ Intensive Care Unit, Wellington Hospital, Wellington, New Zealand.

Abstract

Background: It is unknown whether increasing dietary protein to 1.2-2.0 g/kg/day as recommended in international guidelines compared to current practice improves outcomes in intensive care unit (ICU) patients. The TARGET Protein trial will evaluate this.

Objective: To describe the study protocol for the TARGET Protein trial.

Design setting and participants: TARGET Protein is a cluster randomised, cross-sectional, double cross-over, pragmatic clinical trial undertaken in eight ICUs in Australia and New Zealand. Each ICU will be randomised to use one of two trial enteral formulae for three months before crossing over to the other formula, which is then repeated, with enrolment continuing at each ICU for 12 months. All patients aged ≥16 years in their index ICU admission commencing enteral nutrition will be eligible for inclusion. Eligible patients will receive the trial enteral formula to which their ICU is allocated. The two trial enteral formulae are isocaloric with a difference in protein dose: intervention 100g/1000 ml and comparator 63g/1000 ml. Staggered recruitment commenced in May 2022.

Main outcomes measures: The primary outcome is days free of the index hospital and alive at day 90. Secondary outcomes include days free of the index hospital at day 90 in survivors, alive at day 90, duration of invasive ventilation, ICU and hospital length of stay, incidence of tracheostomy insertion, renal replacement therapy, and discharge destination.

Conclusion: TARGET Protein aims to determine whether augmented enteral protein delivery reduces days free of the index hospital and alive at day 90.

Trial registration: Australian New Zealand Clinical Trials Registry (ACTRN12621001484831).

Keywords: Clinical Outcomes; Critical Illness; Dietary Protein; Enteral Nutrition; Nutrition Therapy.