Clinical trial NCT03992716: Reaching Protein Target With SmofKabiven® Extra Nitrogen vs Olimel N9E During the Early Phase of Acute Critical Illness
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Critical Illness
Lead sponsor: Fresenius Kabi
Sponsor class: INDUSTRY
First posted: 2019-06-20
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients reaching ≥70% of the cumulative target for protein delivery from Study Day 2 through Study Day 6
timeFrame: 5 days
Secondary outcomes:
measure: Percentage of the cumulative target for protein delivery reached from Study Day 2 through Study Day 6
timeFrame: 5 days
measure: Mean cumulative protein delivery by parenteral, enteral, and oral nutrition from Study Day 2 through Study Day 6
timeFrame: 5 days
measure: Calculated mean cumulative protein deficit during the period from Study Day 2 through Study Day 6
timeFrame: 5 days
Other outcomes:
measure: 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)
timeFrame: 5 days
measure: 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
timeFrame: 5 days
measure: Mean daily insulin dose during the 5-day treatment period
timeFrame: 5 days
measure: Mean cumulative insulin dose for the 5-day treatment period
timeFrame: 5 days
measure: Mean change from baseline in daily insulin dose (Study Day 2 through Study Day 6)
timeFrame: 5 days
measure: Maximum single insulin dose during the 5-day treatment period
timeFrame: 5 days
measure: Mean maximum daily blood glucose value during the 5-day treatment period
timeFrame: 5 days
measure: Mean minimum daily blood glucose value during the 5-day treatment period
timeFrame: 5 days
measure: Mean blood glucose value during the 5-day treatment period
timeFrame: 5 days
measure: Mean change from baseline in mean daily blood glucose value (Study Day 2 through Study Day 6)
timeFrame: 5 days
measure: Change from baseline in SOFA score, calculated daily from Study Day 3 through Study Day 7
timeFrame: 5 days
measure: Overall survival time up to Study Day 28
timeFrame: 28 days
measure: All-cause mortality up to Study Day 28
timeFrame: 28 days
measure: Length of stay in the ICU up to Study Day 28
timeFrame: 28 days
measure: Re-admission to ICU up to Study Day 28
timeFrame: 28 days
measure: ICU mortality up to Study Day 28
timeFrame: 28 days
measure: Length of stay in the hospital up to Study Day 28
timeFrame: 28 days
measure: Re-admission to hospital up to Study Day 28
timeFrame: 28 days
measure: Hospital mortality up to Study Day 28
timeFrame: 28 days
measure: Therapeutic Intervention Scoring System (TISS)-28 score (including individual item score, category score, and total score)
timeFrame: Study Day 7
measure: Duration of mechanical ventilation up to Study Day 28
timeFrame: 28 days
measure: Change from baseline of the Medical Research Council (MRC) sum score
timeFrame: Study Day 7, and either on day of ICU discharge or on Study Day 28, whatever occurs first
measure: Change from baseline of ICU Mobility Scale
timeFrame: Study Days 7, 14, and 28
Locations:
city: Paris
country: France
facility: Hôpital Saint-Antoine, Département d'Anesthésie-Réanimation
city: München
country: Germany
facility: Klinikum rechts der Isar, Klinik für Anaesthesiologie
city: Białystok
country: Poland
facility: SP ZOZ Wojewódzki Szpital Zespolony im. J. Śniadeckiego
Study officials:
affiliation: Département d'Anesthésie-Réanimation, Centre Hospitalier Lyon Sud, France
name: Julien Bohe, Prof. MD
role: PRINCIPAL_INVESTIGATOR
References: