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

Phase 4

Terminated

• Conditions: Critical Illness
• Interventions: Drug: Olimel N9E; Drug: SmofKabiven® extra Nitrogen

• Registration Number: NCT03992716
• Lead Sponsor: Fresenius Kabi

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-06-13
• Study First Submitted QC: 2019-06-19
• Study First Posted: 2019-06-20
• Study Start: 2019-11-26
• Primary Completion: 2020-03-24
• Study Completion: 2020-03-24
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-09
• Last Update Posted: 2020-10-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 7

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Olimel N9E	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.
SmofKabiven® extra Nitrogen	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (3)

Hôpital Saint-Antoine, Département d'Anesthésie-Réanimation; 🇫🇷 Paris, France

Klinikum rechts der Isar, Klinik für Anaesthesiologie; 🇩🇪 München, Germany

SP ZOZ Wojewódzki Szpital Zespolony im. J. Śniadeckiego; 🇵🇱 Białystok, Poland