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

Critical Illness Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03992716
• Other study ID #: SKNt-001-CP4
• Secondary ID: 2017-001972-46
• Status: Terminated
• Phase: Phase 4
• Start date: November 26, 2019
• Est. completion date: March 24, 2020

Study information

• Verified date: October 2020
• Source: Fresenius Kabi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: March 24, 2020
• Est. primary completion date: March 24, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 89 Years

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness

Intervention

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.
• 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.

Locations

Country	Name	City	State
France	Hôpital Saint-Antoine, Département d'Anesthésie-Réanimation	Paris
Germany	Klinikum rechts der Isar, Klinik für Anaesthesiologie	München
Poland	SP ZOZ Wojewódzki Szpital Zespolony im. J. Sniadeckiego	Bialystok

Sponsors (1)

Lead Sponsor	Collaborator
Fresenius Kabi

Countries where clinical trial is conducted

France,  Germany,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	Mean daily insulin dose during the 5-day treatment period		5 days
Other	Mean cumulative insulin dose for the 5-day treatment period		5 days
Other	Mean change from baseline in daily insulin dose (Study Day 2 through Study Day 6)		5 days
Other	Maximum single insulin dose during the 5-day treatment period		5 days
Other	Mean maximum daily blood glucose value during the 5-day treatment period		5 days
Other	Mean minimum daily blood glucose value during the 5-day treatment period		5 days
Other	Mean blood glucose value during the 5-day treatment period		5 days
Other	Mean change from baseline in mean daily blood glucose value (Study Day 2 through Study Day 6)		5 days
Other	Change from baseline in SOFA score, calculated daily from Study Day 3 through Study Day 7		5 days
Other	Overall survival time up to Study Day 28		28 days
Other	All-cause mortality up to Study Day 28		28 days
Other	Length of stay in the ICU up to Study Day 28		28 days
Other	Re-admission to ICU up to Study Day 28		28 days
Other	ICU mortality up to Study Day 28		28 days
Other	Length of stay in the hospital up to Study Day 28		28 days
Other	Re-admission to hospital up to Study Day 28		28 days
Other	Hospital mortality up to Study Day 28		28 days
Other	Therapeutic Intervention Scoring System (TISS)-28 score (including individual item score, category score, and total score)		Study Day 7
Other	Duration of mechanical ventilation up to Study Day 28		28 days
Other	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
Other	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
Primary	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	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
Secondary	Mean cumulative protein delivery by parenteral, enteral, and oral nutrition from Study Day 2 through Study Day 6		5 days
Secondary	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