Critical Illness
Conditions
Brief summary
The main focus of the study is to show that SmofKabiven® extra Nitrogen, in a realistic clinical setting, enables to meet high protein requirements in patients during the first week after onset of critical illness, without risk of overfeeding with energy.
Interventions
DRUGSmofKabiven® extra Nitrogen
SmofKabiven® extra Nitrogen (Fresenius Kabi) is a sterile, hypertonic emulsion for parenteral nutrition, in a 3-chamber bag containing amino acids, glucose, a lipid emulsion, and electrolytes.
DRUGOlimel N9E
Olimel N9E (Baxter) is a sterile, hypertonic emulsion for parenteral nutrition, in a 3-chamber bag containing amino acids, glucose, a lipid emulsion, and electrolytes.
Sponsors
Fresenius Kabi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years and \<90 years, male and female 2. Critically ill, medical or surgical ICU patient 3. Admitted to the ICU on the same day or the day before with a minimum expected ICU stay of 3 days 4. Central venous access available for continuous infusion of the study drugs 5. Sequential Organ Failure Assessment (SOFA) score ≥2 6. Contraindication against enteral nutrition or limited tolerance to enteral nutrition and it is planned that patient receives ≥80% of the total target caloric intake from parenteral nutrition during the first 3 nutritional treatment days 7. Written informed consent from the patient or the patient's legal representative or deferred written consent from the patient or patient's legal representative (deferred proxy consent)
Exclusion criteria
1. Contraindication against parenteral nutrition or inability to receive parenteral nutrition via central venous access 2. Received parenteral nutrition within 7 days before randomisation 3. It is planned that patient receives ≥20% of the total target caloric intake via enteral or oral nutrition and/or non-nutritional sources (glucose solution for drug dilution or lipids from propofol/clevidipine or citrate from continuous renal replacement therapy) during the first 3 nutritional treatment days 4. Body mass index (BMI) \<18.5 kg/m2 or \>35 kg/m2 5. Burn injury 6. Any severe, persistent blood coagulation disorder with uncontrolled bleeding 7. Any congenital errors of amino acid metabolism 8. Uncontrolled hyperglycaemia despite insulin treatment 9. Known hypersensitivity to fish, egg, soybean proteins, peanut proteins, or to any of the active substances or excipients contained in SmofKabiven® extra Nitrogen or Olimel N9E 10. Known hypersensitivity to milk protein or to any other substance contained in Fresubin® Original 11. Treatment-refractory cardiopulmonary or metabolic instability showing persistent or progressive worsening despite increased interventions, including severe pulmonary oedema, severe cardiac insufficiency, myocardial infarction, acute phase of circulatory shock, severe sepsis, embolism, haemodynamic instability, metabolic or respiratory acidosis, hypotonic dehydration, or hyperosmolar coma 12. Severe renal dysfunction, defined as serum creatinine ≥2.0 times baseline or urine output \<0.5 mL/kg/h for ≥12 hours (Acute Kidney Injury stage ≥2; \[KDIGO 2012\]), and blood urea nitrogen (BUN) exceeding 2 x upper limit of normal (ULN) 13. Severe liver failure with encephalopathy, including intoxication (e.g. paracetamol, death cap, golden chain) and/or liver enzymes (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], gamma glutamyl transferase \[GGT\]) or bilirubin exceeding 5 x ULN 14. Oncologic disease with anticancer drug and/or radiation treatment incl. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) during this Trial up to and including Study Day 28 15. Preceding transplantation causal for acute critical illness 16. Hemophagocytic syndrome 17. Pregnancy or lactation 18. Receiving end-of-life-care 19. Pathologically altered blood pH (arterial pH \<7.0), oxygen saturation (SaO2 \<80%), or carbon dioxide concentration (PaCO2 ≥80 mm Hg) 20. Hyperlipidaemia or any disorder of lipid metabolism characterised by hypertriglyceridaemia (serum triglyceride levels \>4 mmol/L \[\>350 mg/dL\]) 21. Treatment-refractory, clinically significant major abnormality in the serum concentration of any electrolyte (sodium, potassium, magnesium, total calcium, chloride, inorganic phosphate) 22. Administration of growth hormone including teduglutide within the previous 4 weeks before randomisation 23. Invasive devices and procedures influencing metabolism and organ perfusion, e.g. extracorporeal membrane oxygenation (ECMO), continuous renal replacement therapy (CRRT), molecular absorbent recycling system (MARS), intra-aortic balloon pump (IABP) 24. Receipt of the last dose of study drug in another interventional clinical trial within the previous 4 weeks before randomisation into this clinical trial 25. Previous inclusion in the present study 26. Any other known reason that may prevent a patient to take part in the study in accordance with local requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients reaching ≥70% of the cumulative target for protein delivery from Study Day 2 through Study Day 6 | 5 days | The cumulative target for protein delivery is 6.75 g/kg over 5 Study Days (based on a daily target of 0.75 g/kg/day on Study Day 2 and 1.5 g/kg/day on Study Days 3 through 6); 70% of the cumulative target for protein delivery is 4.73 g/kg. The cumulative protein delivery is calculated as the cumulative intake of amino acids from study drug and protein from enteral or oral nutrition on Study Day 2 through Study Day 6. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of the cumulative target for protein delivery reached from Study Day 2 through Study Day 6 | 5 days | Actual cumulative protein delivery (g/kg/5d) divided by 6.75 (g/kg/5d) and multiplied by 100. |
| Mean cumulative protein delivery by parenteral, enteral, and oral nutrition from Study Day 2 through Study Day 6 | 5 days | — |
| Calculated mean cumulative protein deficit during the period from Study Day 2 through Study Day 6 | 5 days | The cumulative protein deficit is calculated as the cumulative target for protein delivery (6.75 g/kg/5d) minus the actual administered dose (g/kg/5d amino acids from study drug + g/kg/5d from enteral and oral nutrition. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean change from baseline in daily insulin dose (Study Day 2 through Study Day 6) | 5 days | — |
| Maximum single insulin dose during the 5-day treatment period | 5 days | — |
| Mean maximum daily blood glucose value during the 5-day treatment period | 5 days | — |
| Mean minimum daily blood glucose value during the 5-day treatment period | 5 days | — |
| Mean blood glucose value during the 5-day treatment period | 5 days | — |
| Mean change from baseline in mean daily blood glucose value (Study Day 2 through Study Day 6) | 5 days | — |
| Change from baseline in SOFA score, calculated daily from Study Day 3 through Study Day 7 | 5 days | — |
| Overall survival time up to Study Day 28 | 28 days | — |
| All-cause mortality up to Study Day 28 | 28 days | — |
| Mean total cumulative energy intake from parenteral, enteral and oral nutrition and from non-nutritional sources during the 5-day treatment period (calculated for each day from Study Day 2 through Study Day 6) | 5 days | — |
| Re-admission to ICU up to Study Day 28 | 28 days | — |
| ICU mortality up to Study Day 28 | 28 days | — |
| Length of stay in the hospital up to Study Day 28 | 28 days | — |
| Re-admission to hospital up to Study Day 28 | 28 days | — |
| Hospital mortality up to Study Day 28 | 28 days | — |
| Therapeutic Intervention Scoring System (TISS)-28 score (including individual item score, category score, and total score) | Study Day 7 | — |
| Duration of mechanical ventilation up to Study Day 28 | 28 days | — |
| Change from baseline of the Medical Research Council (MRC) sum score | Study Day 7, and either on day of ICU discharge or on Study Day 28, whatever occurs first | — |
| Change from baseline of ICU Mobility Scale | Study Days 7, 14, and 28 | Reference for ICU Mobility Scale: Hodgson C, Needham Dale, Haines K, Bailey M, Ward A, Harrold M, Young P, Zanni J, Buhr H, Higgins A, Presneill J, Berney S. Feasibility and inter-rater reliability of the ICU Mobility scale. Heart Lung 2014; 43(1):19-24. Erratum. Heart Lung 2014;43(4):388. |
| Length of stay in the ICU up to Study Day 28 | 28 days | — |
| Time to increase of daily enteral and oral nutrition intake above 20% of total energy target of 20 kcal/kg/d during the 5-day treatment period | 5 days | — |
| Mean daily insulin dose during the 5-day treatment period | 5 days | — |
| Mean cumulative insulin dose for the 5-day treatment period | 5 days | — |
Countries
France, Germany, Poland
Outcome results
None listed