04 Jan The Effect of early intravenouS amino acid SupplemENtation in criTically Ill pAtients with normaL kidney function：a multi-centered, randomized, parallel-controlled trial

Posted at 09:53h in Clinical Trials, Ongoing Projects by

 

Project abbreviation: ESSENTIAL research

Overall trial start date: 01/06/2020

Overall trial end date: 12/06/2024

Recruitment start date: 01/06/2022

Background and Objective

The 2016 American Society of Critical Care Medicine guidelines for the provision of nutrition support have emphasized the importance of protein intake during critical illness by recommending daily doses as high as two grams per kilogram actual body weight per day [1]. However, because there are no RCTs demonstrating patient-centred benefits arising from this higher protein target, many experts disagree with this recommendation and call for more conservative practice [2]. Recently, Zhu et al published the results from a re-analysis of a large, Phase II, multi-centre clinical trial demonstrating that higher protein intake (2g/kg/day) may significantly reduce 90-day mortality by up to 8% in critically ill patients with normal renal function (P = 0.034) [3]. Given the importance of the benefits demonstrated in the paper by Zhu et al, and the lack of RCTs supporting expert recommendations for protein dosing, we are going to launch a multi-center, randomized, parallel-controlled trial in at least 20 medical or surgical ICUs across China and recruit approximately 1,838 patients during two-year study period.

 

Hypothesis

The hypothesis is that early intravenous amino acid supplementation, compared to routine clinical practice, could reduce 90-day mortality in critically ill patients with normal kidney function.

 

Primary outcome

The primary outcome measure is all-cause mortality at day 90 after randomization.

 

Population

Inclusion Criteria

  1. Informed consent form obtained from the patient or next of kin;
  2. 18 years old or older;
  3. Within 48h of ICU admission;
  4. Expected to stay in ICU for more than 2 days (Ex. Not expected to be discharged on day after enrollment.);
  5. Have a working central venous access line through which the study intervention could be delivered;
  6. Be able to tolerateatleast 1L of fluid volume per day;
  7. APACHEII score ≥ 15 or SOFA score ≥ 6.

 

Exclusion Criteria

  1. Patients iscurrently receiving an selective COX-2 inhibitors;
  2. Patients receiving palliative treatment or expected to die within 48 hours;
  3. Have Acute Kidney Injury, defined as:current serum creatinine (SCr) increased 1.5 times pre-acute illness value OR with recent increase greater than 26.5 µmol/L. [Note: If pre-acute illness creatinine values are unknown, assume upper limit of normal: 90 µmol/L for females and 110 µmol/L for males.]
  4. Patients with malignant diseases receiving radiotherapy or chemotherapy;
  5. Currentlyreceiving or scheduled for dialysis/renal replacement therapy;
  6. Patients ever had a kidney transplant;
  7. Patients require treatment of a burn injury to greater than 20% of total body surface area;
  8. Patients have a documented contraindication to the study intervention (IV amino acids);
  9. Known to be pregnant or currently breastfeeding;
  10. Have severe liver disease (Biopsy proven cirrhosis, or documentedportal hypertension with a known past history of either upper GI bleeding attributed to portal hypertension or of hepatic failure leading to encephalopathy / coma);
  11. Have a documented hypersensitivity (known allergy) to one or moreof the included amino acids;
  12. Have a documented inborn error of amino acid metabolism;

Attachment

ESSENTIAL_StatisticalAnalysisPlan_July30_2024Ver1a.pdf

References

1.Taylor, B. E.; McClave, S. A.; Martindale, R. G.; Warren, M. M.; Johnson, D. R.; Braunschweig, C.; McCarthy, M. S.; Davanos, E.; Rice, T. W.; Cresci, G. A.; Gervasio, J. M.; Sacks, G. S.; Roberts, P. R.; Compher, C.; Society of Critical Care, M.; American Society of, P.; Enteral, N. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). Crit Care Med 2016, 44 (2), 390-438.

2.Rooyackers, O.; Sundstrom Rehal, M.; Liebau, F.; Norberg, A.; Wernerman, J. High protein intake without concerns? Crit Care 2017, 21 (1), 106.

3.Zhu, R.; Allingstrup, M. J.; Perner, A.; Doig, G. S.; Nephro-Protective Trial Investigators, G. The Effect of IV Amino Acid Supplementation on Mortality in ICU Patients May Be Dependent on Kidney Function: Post Hoc Subgroup Analyses of a Multicenter Randomized Trial. Crit Care Med 2018, 46 (8), 1293-1301.