Table 1.

Ongoing studies currently recruiting adult patients (source: Clinicaltrials.gov – Jul 23, 2018)

NCT number	Design	Region	Inclusion criteria	Primary outcome	Secondary outcomes	Intervention	Comparator	Planned sample size
01833624	Open-label PRCT	France	• Traumatic brain injury • Non-traumatic brain injury: stroke, intracranial and/or subarachnoid hemorrhage, subdural and/or extradural hematoma • Expected duration of mechanical ventilation > 48 h	Nutritional efficacy	Morbidity and mortality	Small-peptide enteral feeding formula	Whole-protein formula	206
02509520	PRCT	USA	• Age ≥ 45 years • Respiratory insufficiency requiring mechanical ventilation • ICU presentation < 6 days • All four limbs intact and mobile • Eligible for and able to participate in physical therapy • Pre-admission Barthel Index > 70	-Muscle mass -Global body strength -Mobility status -Short physical performance battery	-Time to weaning -ICU/hospital length of stay -Discharge disposition -Weaning success	Functional strength and cardiopulmonary endurance training MPR and high protein supplement goal of 1.6 g/kg/day protein	“No intervention”: MPR “Active comparator”: MPR and high protein supplement	60
02106624	PRCT	China	• Need mechanical ventilation for more than 2 days • Mean blood pressure more than 60 mmHg • Predicted ICU stay more than 7 days • Tolerance of parenteral or enteral nutrition	28-day and 90-day all cause mortality	-Duration on ventilators -ICU stay -Infection incidence rate -Liver function and renal function -Diameter of midpoint of musculus rectus femoris -Serum concentration of albumin, pre-albumin, retinaldehyde binding protein, transferrin -Change of body composition	Nitrogen supply is as much as 2.5–3.0 g per kilogram (lean mass weight; EN/PN)	1.2–1.5 g per kilogram (lean mass weight; EN/PN)	80
02678325	PRCT	Switzerland	• Adult patients (age 18 years or older) • Expected stay at the ICU of 4 days upon admittance or longer • Expected enteral feeding during at least 4 days	-Amount of protein	-Total amount of calories -Nitrogen balance -Gastric residual -Number of diarrhea events -Occurence of constipation as measured in time without defecation	High protein enteral nutrition formula (caloric density of 1.2 kcal/ml and protein percentage 33% of the total caloric intake)	Standardized normal protein enteral nutrition formula (caloric density of 1.2 kcal/ml and protein 20% of the total caloric intake)	90
02865408	Open-label PRCT	Canada	• Mechanically ventilated adult patients (> 18 years old) admitted to ICU with an expected ICU dependency (alive and need for mechanical ventilation) • Vasopressor therapy, or mechanical circulatory support, at the point of screening of an additional 3 days, as estimated by the treating physician	Whole body protein balance	-Synthesis rates of hepatic secretory proteins -Biomarker of amino acid restriction or repletion -Metabolic substrates -Resting energy expenditure	1.75 g/kg/day of protein (enteral supplemented with IV amino acids)	1.0 g/kg/day of protein (enteral)	30
03021902	Phase II RCT	USA	Requiring mechanical ventilation with actual or expected total duration of mechanical ventilation ≥ 48 h Expected ICU stay ≥ 4 days after enrollment (to permit adequate exposure to the proposed intervention)	-Physical functioning	-Overall strength-upper and lower extremity -Quadriceps force-lower extremity strength -Hand held dynamometry -Distal strength-hand grip strength -Overall physical functional status -Mortality -Length of ventilation -ICU and hospital -ICU readmission -Re-intubation -Hospital-acquired infections -Discharge location (e.g., home vs rehab) -Body composition (ultrasound) -Health-related quality of life -Physical functioning (Katz Index of Independence in Activities of Daily Living) -Physical functioning (mental and cognitive functioning) -Health care resource utilization	IV amino acid (2.0–2.5 g/kg/day) + in-bed cycle ergometry	Usual care	142
03060668	Open-label PRCT	Brazil	•Critically ill patients Mechanically ventilated Expected length in the ICU > 3 days	Physical component of the SF-36	-Handgrip strength -ICU and hospital mortality	Caloric intakes determined by indirect calorimetry + 2.0–2.2 g/kg/day of protein	25 kcal/kg/day and 1.4 to 1.5 g/kg/day of protein	294
03160547	Multi-center pragmatic volunteer-driven registry-based randomized	Canada (over 100 international sites)	Nutritional high-risk Mechanical ventilation	60-day mortality	-Nutritional adequacy -Hospital mortality -Readmission to ICU and hospital -Duration of mechanical ventilation -ICU length of stay -Hospital length of stay	Higher prescription (≥ 2.2 g/kg/day) of protein (EN and/or PN)	A lower prescription (≤ 1.2 g/kg/day) of protein (EN and/or PN)	4000
03170401	PRCT	USA	Trauma/surgery Enteral nutrition expected ≥ 1 week	Serum transthyretin at 3 weeks after injury	-Ventilator-free days -Hospital-acquired pneumonia	Enteral protein supplementation	Standard enteral formula	500
03231540	PRC	Netherlands	• Admitted to intensive care • Mechanically ventilated • Expected duration of ventilation of 72 h • Expected to tolerate and require enteral nutrition for more than 72 h • SOFA score > 6 on admission day	In vitro loss of skeletal muscle function	-Loss of muscle function -Medical research council sum score -Changes in body composition (bioelectrical impedance analysis) -Loss of muscle mass (ultrasound of the quadriceps femoris muscle and diaphragm, questionnaires) -Quality of life	Whey protein supplement enriched enteral nutrition, with protein intake of 1.5 g/kg/day	Standard enteral nutrition, with protein intake of 1 g/kg/day	50
03319836	Retrospective	Canada	ICU patients	Daily total protein intake	-Caloric intake -Feeding interruptions ( tolerance) -Use of inotropes (pressors)	Very high protein enteral nutrition	Standard formula	40

Abbreviations: PRCT prospective randomized controlled trial, ICU intensive care unit, MPR mobility-based physical rehab, EN enteral nutrition, PN parenteral nutrition, SOFA Sequential Organ Failure Assessment