Reaching Protein Target With SmofKabiven® Extra Nitrogen vs Olimel N9E During the Early Phase of Acute Critical Illness

Reaching Protein Target With SmofKabiven® Extra Nitrogen Versus Olimel N9E: A Prospective, Randomised, Active-controlled, Patient-blinded, Multicentre Clinical Trial During the Early Phase of Acute Critical Illness

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.

Study Overview

• Status: Terminated
• Conditions: Critical Illness
• Intervention / Treatment: Drug: SmofKabiven® extra Nitrogen; Drug: Olimel N9E

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Paris, France, 75012
    • Hôpital Saint-Antoine, Département d'Anesthésie-réanimation
• Germany
  • München, Germany, 81675
    • Klinikum rechts der Isar, Klinik für Anaesthesiologie
• Poland
  • Białystok, Poland, 15-897
    • SP ZOZ Wojewodzki Szpital Zespolony im. J. Sniadeckiego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 87 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SmofKabiven® extra Nitrogen; Parenteral nutrition with SmofKabiven® extra Nitrogen in a dosage to provide 10 kcal/kg/day on Study Day 2 and 20 kcal/kg/day on Study Days 3 through 6.	Drug: SmofKabiven® 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.
Active Comparator: Olimel N9E; Parenteral nutrition with Olimel N9E in a dosage to provide 10 kcal/kg/day on Study Day 2 and 20 kcal/kg/day on Study Days 3 through 6.	Drug: Olimel 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients reaching ≥70% of the cumulative target for protein delivery from Study Day 2 through Study Day 6	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.	5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of the cumulative target for protein delivery reached from Study Day 2 through Study Day 6	Actual cumulative protein delivery (g/kg/5d) divided by 6.75 (g/kg/5d) and multiplied by 100.	5 days
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	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.	5 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Length of stay in the ICU up to Study Day 28		28 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	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.	Study Days 7, 14, and 28

Collaborators and Investigators

• Sponsor: Fresenius Kabi
• Investigators: Principal Investigator: Julien Bohe, Prof. MD, Département d'Anesthésie-Réanimation, Centre Hospitalier Lyon Sud, France

Study record dates

Study Major Dates

• Study Start (Actual): November 26, 2019
• Primary Completion (Actual): March 24, 2020
• Study Completion (Actual): March 24, 2020

Study Registration Dates

• First Submitted: June 13, 2019
• First Submitted That Met QC Criteria: June 19, 2019
• First Posted (Actual): June 20, 2019

Study Record Updates

• Last Update Posted (Actual): October 14, 2020
• Last Update Submitted That Met QC Criteria: October 9, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: SKNt-001-CP4; 2017-001972-46 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No