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Randomized Controlled Trial
. 2025 Jul 22;334(4):319-328.
doi: 10.1001/jama.2025.9110.

Augmented Enteral Protein During Critical Illness: The TARGET Protein Randomized Clinical Trial

Matthew J Summers  1   2 , Lee-Anne S Chapple  1   2   3   4 , Amalia Karahalios  5   6 , Rinaldo Bellomo  4   7   8 , Marianne J Chapman  1   2   3   4 , Suzie Ferrie  9   10 , Mark E Finnis  1   2   4   8 , Craig French  8   11 , Sally Hurford  12 , Nima Kakho  13 , Matthew J Maiden  8   13   14 , Stephanie N O'Connor  1   2 , Sandra L Peake  1   4   15 , Jeffrey J Presneill  4   8   14 , Emma J Ridley  4   16 , An Tran-Duy  6   17 , Patricia J Williams  1   4   15 , Paul J Young  8   11   18 , Sophie Zaloumis  5   6 , Adam M Deane  8   14 ; TARGET Protein Investigators and for the Australian and New Zealand Intensive Care Society Clinical Trials Group
Collaborators, Affiliations
Randomized Controlled Trial

Augmented Enteral Protein During Critical Illness: The TARGET Protein Randomized Clinical Trial

Matthew J Summers et al. JAMA. .

Abstract

Importance: Guidelines recommend augmenting enteral protein during critical illness, but the impact on patient outcomes is uncertain.

Objective: To determine whether augmenting enteral protein increases days alive and free from hospitalization.

Design, setting, and participants: 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.

Intervention: 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.

Main outcomes and measures: 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.

Results: 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 -1.97 (95% CI, -7.24 to 3.30) days (P = .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, -1.94 to 1.96) days; difference in mean duration of invasive ventilation, 6.8 (95% CI, -3.0 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.

Conclusions and relevance: Augmenting enteral protein during critical illness did not improve number of days free of the index hospital and alive at day 90.

Trial registration: ANZCTR Identifier: ACTRN12621001484831.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Chapple reported receiving personal fees from Nutricia and Fresenius Kabi outside the submitted work. Dr Karahalios reported receiving grants from Medical Research Future Fund during the conduct of the study. Dr Chapman reported receiving grants from National Health and Medical Research Council (NHMRC) during the conduct of the study. Dr French reported receiving grants from NHMRC during the conduct of the study. Dr Presneill reported receiving grants from Australian Government Medical Research Future Fund (grant application number 2014786), Australian and New Zealand Intensive Care Foundation Project (grant project identification number: 2138), and Nutricia Australia Pty Limited to support the costs of the trial enteral formulae during the conduct of the study. Dr Ridley reported receiving personal fees from Nutricia Australia and personal fees from Fresenius Kabi Australia outside the submitted work. Dr Young reported receiving grants from Health Research Council of New Zealand outside the submitted work. Dr Deane reported receiving grants from National Health and Medical Research Council Medical Research Future Fund, Australian and New Zealand Intensive Care Foundation, Nutricia Australia Pty Limited, and National Health and Medical Research Council and lecture fees paid to institution from Baxter Healthcare during the conduct of the study. No other disclosures were reported.

References

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