Augmented Enteral Protein During Critical IllnessThe TARGET Protein Randomized Clinical Trial

Matthew J. Summers, BSc, MDiet1,2; Lee-anne S. Chapple, PhD1,2,3,4; Amalia Karahalios, PhD5,6; et al

2025년 06월11일

JAMA. Published online 252; 334; (4) : 319-328.

DOI: 10.1001/jama.2025.9110

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.

Key Points

Question  Does augmentation of enteral protein improve outcomes in critically ill patients?

Findings  In this cluster randomized, crossover, open-label trial of 3397 patients from 8 intensive care units, additional enteral protein did not increase days free of the index hospital and alive at day 90 compared with usual care (median difference, −1.97 days).

Meaning  Augmenting enteral protein for patients in the intensive care unit does not improve outcomes.

요약

·         중요성 : 가이드라인에서는 중환자 상태에서 장관 단백질 공급을 늘리도록 권고하지만, 실제로 환자 예후 개선 효과는 불확실하다.

·         목적 : 장관 단백질 증량이 병원에 입원하지 않고 생존한 일수를 증가시키는지 평가한다.

·         설계, 환경 및 참가자 : 군집 무작위, 교차, 공개 라벨 시험으로, 2022년 5월 23일~2023년 8월 23일까지 호주·뉴질랜드 8개 ICU에서 장관영양을 받는 중환자를 대상으로 하였으며, 최종 추적은 2023년 11월 21일까지였다.

·         중재 : 고단백군(증량단백질, 100 g/L)과 일반단백질군(63 g/L) 으로 배정하고, 12개월 동안 각 3개월씩 순차적으로 두 가지 영양제를 사용했으며, 4개 ICU는 고단백질 식이로 시작했고 나머지 4개 ICU는 일반 단백질 식이로 시작하였다.

·         주요 결과 및 측정 :

-1차: 90일째 병원에서 벗어나 생존한 일수

-2차: 90일 생존율, 생존자에서 병원 벗어난 일수, 인공호흡기 사용 기간, ICU/병원 재원 기간, 기관절개술, 신대체요법 필요 여부, 퇴원 장소

·          결과 : 총 3,397명 포함(연령 중앙값 61세; 남성 64%).

• 1차지표 -90일째 병원 벗어나 생존한 일수

  고단백질군: 62일 (IQR 0~77일)

  일반단백질군: 64일 (IQR 0~77일)

교차 효과 보정 후 중앙값 차이: −1.97일 (95% CI −7.24~3.30; P=0.46)

- 90일 생존율

  고단백질군: 72.6%

   일반단백질군: 74.0%

RR 0.99 (95% CI 0.95~1.03)

• 2차지표 -생존자 병원 벗어난 일수 차이: 0.01일 (95% CI −1.94~1.96)

- 인공호흡기 사용 기간 평균 차이: 6.8시간 (95% CI −3.0~16.5)

- ICU 생존퇴실 HR 0.93 (95% CI 0.88~1.00)

-병원 생존퇴원 HR 0.96 (95% CI 0.90~1.02)

-기관절개술 RR 1.15 (95% CI 0.66~2.01)

-신대체요법 RR 0.97 (95% CI 0.81~1.16)

-퇴원 장소 유의한 차이 없음

·         결론 및 의의 : 중환자에게 장관 단백질을 증량해도 90일째 병원을 벗어나 생존한 일수를 늘리지 못했으며, 다른 임상결과에서도 개선 효과가 없었다.