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出境医 / 临床实验 / 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 vs Olimel N9E During the Early Phase of Acute Critical Illness

Study Description
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.

Condition or disease Intervention/treatment Phase
Critical Illness Drug: SmofKabiven® extra Nitrogen Drug: Olimel N9E Phase 4

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Supportive Care
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
Actual Study Start Date : November 26, 2019
Actual Primary Completion Date : March 24, 2020
Actual Study Completion Date : March 24, 2020
Arms and Interventions
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.
Outcome Measures
Primary Outcome Measures :
  1. Proportion of patients reaching ≥70% of the cumulative target for protein delivery from Study Day 2 through Study Day 6 [ Time Frame: 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 :
  1. Percentage of the cumulative target for protein delivery reached from Study Day 2 through Study Day 6 [ Time Frame: 5 days ]
    Actual cumulative protein delivery (g/kg/5d) divided by 6.75 (g/kg/5d) and multiplied by 100.

  2. Mean cumulative protein delivery by parenteral, enteral, and oral nutrition from Study Day 2 through Study Day 6 [ Time Frame: 5 days ]
  3. Calculated mean cumulative protein deficit during the period from Study Day 2 through Study Day 6 [ Time Frame: 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 Outcome Measures:
  1. 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) [ Time Frame: 5 days ]
  2. 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 [ Time Frame: 5 days ]
  3. Mean daily insulin dose during the 5-day treatment period [ Time Frame: 5 days ]
  4. Mean cumulative insulin dose for the 5-day treatment period [ Time Frame: 5 days ]
  5. Mean change from baseline in daily insulin dose (Study Day 2 through Study Day 6) [ Time Frame: 5 days ]
  6. Maximum single insulin dose during the 5-day treatment period [ Time Frame: 5 days ]
  7. Mean maximum daily blood glucose value during the 5-day treatment period [ Time Frame: 5 days ]
  8. Mean minimum daily blood glucose value during the 5-day treatment period [ Time Frame: 5 days ]
  9. Mean blood glucose value during the 5-day treatment period [ Time Frame: 5 days ]
  10. Mean change from baseline in mean daily blood glucose value (Study Day 2 through Study Day 6) [ Time Frame: 5 days ]
  11. Change from baseline in SOFA score, calculated daily from Study Day 3 through Study Day 7 [ Time Frame: 5 days ]
  12. Overall survival time up to Study Day 28 [ Time Frame: 28 days ]
  13. All-cause mortality up to Study Day 28 [ Time Frame: 28 days ]
  14. Length of stay in the ICU up to Study Day 28 [ Time Frame: 28 days ]
  15. Re-admission to ICU up to Study Day 28 [ Time Frame: 28 days ]
  16. ICU mortality up to Study Day 28 [ Time Frame: 28 days ]
  17. Length of stay in the hospital up to Study Day 28 [ Time Frame: 28 days ]
  18. Re-admission to hospital up to Study Day 28 [ Time Frame: 28 days ]
  19. Hospital mortality up to Study Day 28 [ Time Frame: 28 days ]
  20. Therapeutic Intervention Scoring System (TISS)-28 score (including individual item score, category score, and total score) [ Time Frame: Study Day 7 ]
  21. Duration of mechanical ventilation up to Study Day 28 [ Time Frame: 28 days ]
  22. Change from baseline of the Medical Research Council (MRC) sum score [ Time Frame: Study Day 7, and either on day of ICU discharge or on Study Day 28, whatever occurs first ]
  23. Change from baseline of ICU Mobility Scale [ Time Frame: 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.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations

Locations
Layout table for location information
France
Hôpital Saint-Antoine, Département d'Anesthésie-Réanimation
Paris, France, 75012
Germany
Klinikum rechts der Isar, Klinik für Anaesthesiologie
München, Germany, 81675
Poland
SP ZOZ Wojewódzki Szpital Zespolony im. J. Śniadeckiego
Białystok, Poland, 15-897
Sponsors and Collaborators
Fresenius Kabi
Investigators
Layout table for investigator information
Principal Investigator: Julien Bohe, Prof. MD Département d'Anesthésie-Réanimation, Centre Hospitalier Lyon Sud, France
Tracking Information
First Submitted Date  ICMJE June 13, 2019
First Posted Date  ICMJE June 20, 2019
Last Update Posted Date October 14, 2020
Actual Study Start Date  ICMJE November 26, 2019
Actual Primary Completion Date March 24, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 19, 2019) 		Proportion of patients reaching ≥70% of the cumulative target for protein delivery from Study Day 2 through Study Day 6 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 19, 2019)
  • Percentage of the cumulative target for protein delivery reached from Study Day 2 through Study Day 6 [ Time Frame: 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 [ Time Frame: 5 days ]
  • Calculated mean cumulative protein deficit during the period from Study Day 2 through Study Day 6 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 19, 2019)
  • 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) [ Time Frame: 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 [ Time Frame: 5 days ]
  • Mean daily insulin dose during the 5-day treatment period [ Time Frame: 5 days ]
  • Mean cumulative insulin dose for the 5-day treatment period [ Time Frame: 5 days ]
  • Mean change from baseline in daily insulin dose (Study Day 2 through Study Day 6) [ Time Frame: 5 days ]
  • Maximum single insulin dose during the 5-day treatment period [ Time Frame: 5 days ]
  • Mean maximum daily blood glucose value during the 5-day treatment period [ Time Frame: 5 days ]
  • Mean minimum daily blood glucose value during the 5-day treatment period [ Time Frame: 5 days ]
  • Mean blood glucose value during the 5-day treatment period [ Time Frame: 5 days ]
  • Mean change from baseline in mean daily blood glucose value (Study Day 2 through Study Day 6) [ Time Frame: 5 days ]
  • Change from baseline in SOFA score, calculated daily from Study Day 3 through Study Day 7 [ Time Frame: 5 days ]
  • Overall survival time up to Study Day 28 [ Time Frame: 28 days ]
  • All-cause mortality up to Study Day 28 [ Time Frame: 28 days ]
  • Length of stay in the ICU up to Study Day 28 [ Time Frame: 28 days ]
  • Re-admission to ICU up to Study Day 28 [ Time Frame: 28 days ]
  • ICU mortality up to Study Day 28 [ Time Frame: 28 days ]
  • Length of stay in the hospital up to Study Day 28 [ Time Frame: 28 days ]
  • Re-admission to hospital up to Study Day 28 [ Time Frame: 28 days ]
  • Hospital mortality up to Study Day 28 [ Time Frame: 28 days ]
  • Therapeutic Intervention Scoring System (TISS)-28 score (including individual item score, category score, and total score) [ Time Frame: Study Day 7 ]
  • Duration of mechanical ventilation up to Study Day 28 [ Time Frame: 28 days ]
  • Change from baseline of the Medical Research Council (MRC) sum score [ Time Frame: 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 [ Time Frame: 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.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Reaching Protein Target With SmofKabiven® Extra Nitrogen vs Olimel N9E During the Early Phase of Acute Critical Illness
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Supportive Care
Condition  ICMJE Critical Illness
Intervention  ICMJE
  • 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.
  • 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.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: SmofKabiven® extra Nitrogen
  • 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.
    Intervention: Drug: Olimel N9E
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 9, 2020) 		7
Original Estimated Enrollment  ICMJE
 (submitted: June 19, 2019) 		120
Actual Study Completion Date  ICMJE March 24, 2020
Actual Primary Completion Date March 24, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 89 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Germany,   Poland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03992716
Other Study ID Numbers  ICMJE SKNt-001-CP4
2017-001972-46 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Fresenius Kabi
Study Sponsor  ICMJE Fresenius Kabi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Julien Bohe, Prof. MD Département d'Anesthésie-Réanimation, Centre Hospitalier Lyon Sud, France
PRS Account Fresenius Kabi
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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