Efficacy & Safety of SmofKabiven Emulsion for Infusion vs Hospital Compounded "All in One" for Parenteral Nutrition

Efficacy & Safety of SmofKabiven Emulsion for Infusion vs Hospital Compounded "All in One" for Parenteral Nutrition (PN): A Randomized, Active-Controlled, Patient-blinded, Multi-Centre Study in Adult Surgical Patients Requiring PN

The present protocol describes a randomized, patient-blinded study in which either SmofKabiven emulsion for infusion or a hospital compounded "All in one" control Total Parenteral Nutrition (TPN) regimen will be given to adult surgical patients for 5 consecutive days.

As serum prealbumin is a well-established surrogate efficacy parameter reflecting the patient´s nutritional status, the change of the serum prealbumin level at the day of the final study visit compared to baseline will represent the primary efficacy parameter in the present study.

Study Overview

• Status: Completed
• Conditions: Surgery; Parenteral Nutrition
• Intervention / Treatment: Drug: SmofKabiven emulsion for infusion; Drug: Hospital compounded "All in one" emulsion

Detailed Description

In addition, other variables will be assessed in this study, i.e., postsurgical new onset of nosocomial infection, CRP, free fatty acids, immunology parameters, the results of physical examination, vital signs, relevant nutrition- and safety-related laboratory parameters in venous blood and urine, the results of an Electrocardiography (ECG), and the number, severity, seriousness, clinical relevance, relatedness and outcome of Adverse Events (AEs). The aim of the planned study is to demonstrate that SmofKabiven emulsion for infusion is not inferior to the comparative drug (hospital compounded "All in one" emulsion for parenteral nutrition).

• Study Type: Interventional
• Enrollment (Actual): 273
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Beijing Friendship Hospital, Capital Medical University
  • Changchun, China
    • The Second Hospital of Jilin University
  • Guangzhou, China
    • The First Affiliated Hospital of Guangzhou Medical University
  • Nanning, China
    • Thepeople's hospital of Guangxi zhuang
  • Shanghai, China
    • Shanghai First People's Hospital
  • Shanghai, China
    • Zhongshan Hospital Fudan University
  • Shanghai, China
    • Shanghai Pudong Hospital
  • Taiyuan, China
    • Shanxi Provincial People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient is scheduled to undergo elective gastrointestinal surgery;
2. Female or male patients, age ≥ 18 and ≤ 80 years;
3. Postoperatively, patient is expected to receive 100% of the total daily energy demand via PN for at least 5 consecutive days;
4. Body Mass Index (BMI) ≥ 16 kg/m2 and ≤ 30 kg /m2, and actual body weight ≥ 40 kg;
5. Patient is capable to give Informed Consent, agrees to participate in the study, and signs the Informed Consent Form.

Exclusion Criteria:

1. Patient has received PN or parenteral amino acids in the last 10 days before randomization (exception: administration of glucose will be allowed);
2. Known severe liver insufficiency in the medical history, or AST or ALT at least 3.0-times higher than the upper limit of normal range or total bilirubin at least 1.5-times higher than the upper limit of normal range;
3. International Normalised Ratio (INR) at least 1.5 times higher than the upper limit of normal range;
4. Uncontrolled hyperglycaemia defined as fasting blood glucose > 180 mg/ dl (10 mmol/L);
5. Severe renal impairment defined as serum creatinine value at least 1.5 times higher than the upper limit of normal range;
6. Serious hyperlipidaemia (serum cholesterol and/or triglycerides and/or LDL-C level at least 1.5 times higher than the upper limit of normal range);
7. Known inborn abnormality of amino acid metabolism in the medical history;
8. Known acute pancreatitis in the medical history;
9. Known hypothyroidism or hyperthyroidism in the medical history;
10. Serum level of any of the electrolytes (sodium, potassium, magnesium, total calcium, chloride, phosphate) above the upper limit of the normal range;
11. Known unstable metabolism in the medical history (e.g., metabolic acidosis);
12. Known hypersensitivity to fish, egg, soybean, or peanut protein or to any of the active substances or excipients of the study drugs in the medical history;
13. General contraindications to infusion therapy: acute pulmonary oedema, hyperhydration, and decompensated cardiac insufficiency /congestive heart failure;
14. Unstable haemodynamic conditions (e.g., acute myocardial infarction, stroke, embolism, severe sepsis, shock);
15. Known hemophagocytic syndrome;
16. Patients diagnosed with an infection before the surgery;
17. Drug abuse and/or chronic alcoholism;
18. Psychiatric diseases, epilepsy;
19. Administration of growth hormones within the previous 4 weeks before surgery, or chronic maintenance therapy with systemic glucocorticoids 4 weeks before surgery;
20. Participation in a clinical study with an investigational drug or an investigational medical device within one month prior to start of study or during study;
21. Patient is pregnant or lactating and intends to continue breast-feeding;

22. Development of intraoperative/ postoperative conditions (assessed after surgery and before enrolment of patients):

    1. Intra-operative blood loss > 1000 ml;
    2. Development of a condition in which PN is contraindicated;
    3. Intra- or postoperative urine output < 0.5 ml/kg/h;
    4. Need for postoperative haemofiltration or dialysis;
    5. Contraindication or inability to obtain central venous catheter access;
    6. Intra-operative decision on limited treatment, e.g. due to diagnosis of carcinomatosis;
    7. Intra-operative severe complications including resuscitation, hemorrhagic and septic shock, acute single and multiple organ dysfunction including pulmonary, hepatic, and renal dysfunction prohibiting early postsurgical extubation, requiring liver-specific treatment and renal replacement therapy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SmofKabiven emulsion for infusion; SmofKabiven emulsion for infusion will be continuously infused intravenously via central venous access for approximately 14-24 h/d. Duration of treatment with the study drug is 5 consecutive days.Targeted daily dose is 26.3 ml/kg bw/day resulting in 29.3 kcal/kg bw/day. Dosage on D 1 will be reduced to 50%.	Drug: SmofKabiven emulsion for infusion; Total Parenteral Nutrition; Other Names: Investigational Product; Study intervention
Active Comparator: Hospital compounded "All in one" emulsion for PN; Hospital compounded "All in one" emulsion will be continuously infused intravenously via central venous access for approximately 14-24 h/d. Duration of treatment with the study drugs will be 5 consecutive days.Targeted daily dose is 26.3 ml/kg bw/day resulting in 29.3 kcal/kg bw/day. Dosage on D 1 will be reduced to 50%.	Drug: Hospital compounded "All in one" emulsion; Total Parenteral Nutrition; Other Names: Control; Comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Prealbumin	Change in Serum Prealbumin	6 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nosocomial infection	Postsurgical new onset of nosocomial infection	6 days
Prealbumin	Change in Prealbumin	4 days
C-reactive Protein (CRP)	Change in CRP	6 days
Linoleic acid	Change in linoleic acid	6 days
Linolenic acid	Change in linolenic acid	6 days
Arachidonic acid	Change in arachidonic acid	6 days
Eicosapentaenoic acid (EPA)	Change in EPA	6 days
Docosahexaenoic acis (DHA)	Change in DHA	6 days
Thromboxane B3 (TX B3) / Thromboxane B2 (TX B2)	Change in TX B3/B2	6 days
Interleukin (IL)-1	Change in IL-1	6 days
Interleukin (IL)-2	Change in IL-2	6 days
Interleukin (IL)-6	Change in IL-6	6 days
Cluster of Differentiation 4 (CD4) / Cluster of Differentiation 8 (CD8)	Change in CD4/CD8	6 days
Plasma amino acid (taurine)	Change in taurine	6 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AE)	Coded according to Medical Dictionary for Regulatory Affairs (MedDRA) by System Organ Class (SOC) and preferred term	up to 16 days
Blood pressure	Vital signs	up to 16 days
Heart rate	Vital signs	up to 16 days
Respiratory rate	Vital signs	up to 16 days
Axillary body temperature	Vital signs	up to 16 days
Physical examination	Examination of abnormal findings in any system/organ	up to 16 days
Red blood cell (RBC) count	Laboratory variable	up to 16 days
Total white blood cell (WBC) count	Laboratory variable	up to 16 days
Haemoglobin (Hb)	Laboratory variable	up to 16 days
Haematocrit (Hct)	Laboratory variable	up to 16 days
Platelets	Laboratory variable	up to 16 days
Creatinine	Laboratory variable	up to 16 days
Urea	Laboratory variable	up to 16 days
Sodium	Laboratory variable	up to 16 days
Potassium	Laboratory variable	up to 16 days
Magnesium	Laboratory variable	up to 16 days
Total calcium	Laboratory variable	up to 16 days
Chloride	Laboratory variable	up to 16 days
Phosphate	Laboratory variable	up to 16 days
Aspartate aminotransferase (AST)	Laboratory variable	up to 16 days
Alanine aminotransferase (ALT)	Laboratory variable	up to 16 days
Alkaline phosphatase (AP)	Laboratory variable	up to 16 days
Gamma-glutamyl transpeptidase (γ-GT)	Laboratory variable	up to 16 days
Lactate dehydrogenase (LDH)	Laboratory variable	up to 16 days
Total and direct bilirubin	Laboratory variable	up to 16 days
Albumin	Laboratory variable	up to 16 days
Total protein	Laboratory variable	up to 16 days
Glucose	Laboratory variable	up to 16 days
Cholesterol	Laboratory variable	up to 16 days
Triglycerides	Laboratory variable	up to 16 days
Low Density Lipoprotein (LDL)-C	Laboratory variable	up to 16 days
High Density Lipoprotein (HDL)-C	Laboratory variable	up to 16 days
Fibrinogen	Laboratory variable	up to 16 days
Activated partial thromboplastin time (APTT)	Laboratory variable	up to 16 days
Prothrombin time (PT)	Laboratory variable	up to 16 days
International Normalised Ratio (INR)	Laboratory variable	up to 16 days
Power of water (pH) value	Urine analysis	up to 16 days
Bilirubin	Urine analysis	up to 16 days
Protein	Urine analysis	up to 16 days
White Blood Cell (WBC)	Urine analysis	up to 16 days
Red Blood Cell (RBC)	Urine analysis	up to 16 days
Urine Glucose	Urine analysis	up to 16 days
Ketone body	Urine analysis	up to 16 days
Electrocardiogram (ECG)	Electrocardiogram to assess cardiac disorders (e.g. Myocardial infarction, Pericarditis, QT interval Prolongation, etc.)	up to 16 days

Collaborators and Investigators

• Sponsor: Fresenius Kabi
• Collaborators: Parexel
• Investigators: Principal Investigator: Zhang Zhongtao, MD, Beijing Friendship Hospital

Publications and helpful links

General Publications

• Klevens RM, Edwards JR, Richards CL Jr, Horan TC, Gaynes RP, Pollock DA, Cardo DM. Estimating health care-associated infections and deaths in U.S. hospitals, 2002. Public Health Rep. 2007 Mar-Apr;122(2):160-6. doi: 10.1177/003335490712200205.
• McClave SA, Martindale RG, Vanek VW, McCarthy M, Roberts P, Taylor B, Ochoa JB, Napolitano L, Cresci G; A.S.P.E.N. Board of Directors; American College of Critical Care Medicine; Society of Critical Care Medicine. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr. 2009 May-Jun;33(3):277-316. doi: 10.1177/0148607109335234. No abstract available.
• Gura KM, Duggan CP, Collier SB, Jennings RW, Folkman J, Bistrian BR, Puder M. Reversal of parenteral nutrition-associated liver disease in two infants with short bowel syndrome using parenteral fish oil: implications for future management. Pediatrics. 2006 Jul;118(1):e197-201. doi: 10.1542/peds.2005-2662.
• Puder M, Valim C, Meisel JA, Le HD, de Meijer VE, Robinson EM, Zhou J, Duggan C, Gura KM. Parenteral fish oil improves outcomes in patients with parenteral nutrition-associated liver injury. Ann Surg. 2009 Sep;250(3):395-402. doi: 10.1097/SLA.0b013e3181b36657.
• Alwayn IP, Gura K, Nose V, Zausche B, Javid P, Garza J, Verbesey J, Voss S, Ollero M, Andersson C, Bistrian B, Folkman J, Puder M. Omega-3 fatty acid supplementation prevents hepatic steatosis in a murine model of nonalcoholic fatty liver disease. Pediatr Res. 2005 Mar;57(3):445-52. doi: 10.1203/01.PDR.0000153672.43030.75. Epub 2005 Jan 19.
• Horan TC, Gaynes RP, Martone WJ, Jarvis WR, Emori TG. CDC definitions of nosocomial surgical site infections, 1992: a modification of CDC definitions of surgical wound infections. Am J Infect Control. 1992 Oct;20(5):271-4. doi: 10.1016/s0196-6553(05)80201-9. No abstract available.
• Calder PC. n-3 fatty acids, inflammation, and immunity--relevance to postsurgical and critically ill patients. Lipids. 2004 Dec;39(12):1147-61. doi: 10.1007/s11745-004-1342-z.
• Mayer K, Gokorsch S, Fegbeutel C, Hattar K, Rosseau S, Walmrath D, Seeger W, Grimminger F. Parenteral nutrition with fish oil modulates cytokine response in patients with sepsis. Am J Respir Crit Care Med. 2003 May 15;167(10):1321-8. doi: 10.1164/rccm.200207-674OC. Epub 2003 Feb 25.
• Novak TE, Babcock TA, Jho DH, Helton WS, Espat NJ. NF-kappa B inhibition by omega -3 fatty acids modulates LPS-stimulated macrophage TNF-alpha transcription. Am J Physiol Lung Cell Mol Physiol. 2003 Jan;284(1):L84-9. doi: 10.1152/ajplung.00077.2002. Epub 2002 Aug 30.
• Pluess TT, Hayoz D, Berger MM, Tappy L, Revelly JP, Michaeli B, Carpentier YA, Chiolero RL. Intravenous fish oil blunts the physiological response to endotoxin in healthy subjects. Intensive Care Med. 2007 May;33(5):789-797. doi: 10.1007/s00134-007-0591-5. Epub 2007 Mar 22. Erratum In: Intensive Care Med. 2007 Jul;33(7):1310.
• Xiong J, Zhu S, Zhou Y, Wu H, Wang C. Regulation of omega-3 fish oil emulsion on the SIRS during the initial stage of severe acute pancreatitis. J Huazhong Univ Sci Technolog Med Sci. 2009 Feb;29(1):35-8. doi: 10.1007/s11596-009-0107-3. Epub 2009 Feb 18.
• Helmut Grimm, A balanced lipid emulsion-A new concept in parenteral nutrition. Clinical Nutrition Supplements (2005) 1, 25-30.
• Grimm H, Mertes N, Goeters C, Schlotzer E, Mayer K, Grimminger F, Furst P. Improved fatty acid and leukotriene pattern with a novel lipid emulsion in surgical patients. Eur J Nutr. 2006 Feb;45(1):55-60. doi: 10.1007/s00394-005-0573-8. Epub 2005 Jul 22.
• Bouletreau P, Chassard D, Allaouchiche B, Dumont JC, Auboyer C, Bertin-Maghit M, Bricard H, Ecochard R, Rangaraj J, Chambrier C, Schneid C, Cynober L. Glucose-lipid ratio is a determinant of nitrogen balance during total parenteral nutrition in critically ill patients: a prospective, randomized, multicenter blind trial with an intention-to-treat analysis. Intensive Care Med. 2005 Oct;31(10):1394-400. doi: 10.1007/s00134-005-2771-5. Epub 2005 Aug 24.
• Sergi G, Coin A, Enzi G, Volpato S, Inelmen EM, Buttarello M, Peloso M, Mulone S, Marin S, Bonometto P. Role of visceral proteins in detecting malnutrition in the elderly. Eur J Clin Nutr. 2006 Feb;60(2):203-9. doi: 10.1038/sj.ejcn.1602289.
• Shenkin A. Serum prealbumin: Is it a marker of nutritional status or of risk of malnutrition? Clin Chem. 2006 Dec;52(12):2177-9. doi: 10.1373/clinchem.2006.077412. No abstract available.
• Young GA, Hill GL. Assessment of protein-calorie malnutrition in surgical patients from plasma proteins and anthropometric measurements. Am J Clin Nutr. 1978 Mar;31(3):429-35. doi: 10.1093/ajcn/31.3.429.
• Young GA, Collins JP, Hill GL. Plasma proteins in patients receiving intravenous amino acids or intravenous hyperalimentation after major surgery. Am J Clin Nutr. 1979 Jun;32(6):1192-9. doi: 10.1093/ajcn/32.6.1192.
• Young GA, Hill GL. A controlled study of protein-sparing therapy after excision of the rectum: effects of intravenous amino acids and hyperalimentation on body composition and plasma amino acids. Ann Surg. 1980 Aug;192(2):183-91. doi: 10.1097/00000658-198008000-00009.
• Chinese medical clinical guidelines parenteral enteral nutrition 2008, edited by Chinese Medical Association, People's Medical Publishing House.
• Fresenius Kabi SSPC. Intralipid 20%, Summary of Product Characteristics, dated 14 February 2007.
• Bernstein LH. The systemic inflammatory response syndrome C-reactive protein and transthyretin conundrum. Clin Chem Lab Med. 2007;45(11):1566-7; author reply 1568-9. doi: 10.1515/CCLM.2007.334. No abstract available.
• Fresenius Kabi SSPC. Novamin 11.4%, Summary of Product Characteristics, dated 01 December 2013.
• Braga M, Ljungqvist O, Soeters P, Fearon K, Weimann A, Bozzetti F; ESPEN. ESPEN Guidelines on Parenteral Nutrition: surgery. Clin Nutr. 2009 Aug;28(4):378-86. doi: 10.1016/j.clnu.2009.04.002. Epub 2009 May 21.
• Chowdary KV, Reddy PN. Parenteral nutrition: Revisited. Indian J Anaesth. 2010 Mar;54(2):95-103. doi: 10.4103/0019-5049.63637.
• Singer P, Berger MM, Van den Berghe G, Biolo G, Calder P, Forbes A, Griffiths R, Kreyman G, Leverve X, Pichard C, ESPEN. ESPEN Guidelines on Parenteral Nutrition: intensive care. Clin Nutr. 2009 Aug;28(4):387-400. doi: 10.1016/j.clnu.2009.04.024. Epub 2009 Jun 7.
• Fresenius Kabi. SomfKabiven emulsion for infusion. Summary of Product Characteristics, dated December 08. 2008.
• ZHAO Subin, GU Junxia, ZHANG Xianbin, SHI Dongfang, Early enteral nutrition with Fresubin after gastrointestinal operation, Parenteral& Enteral Nutrition, Ju1．2003, Vol l0 No.3: 134-136.
• Wei Yi Fa (2001) No.2: Notice for Ministry of Health of China to Publish the Diagnosis Criteria of Nosocomial Infection (Pilot Edition). Ministry of Health of China Office, Jan.2, 200.

Helpful Links

• International Council for Harmonisation (ICH) E10 'Note for Guidance on Choice of Control Group', July 2000

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2019
• Primary Completion (Actual): January 23, 2020
• Study Completion (Actual): January 23, 2020

Study Registration Dates

• First Submitted: November 14, 2018
• First Submitted That Met QC Criteria: January 2, 2019
• First Posted (Actual): January 3, 2019

Study Record Updates

• Last Update Posted (Actual): August 2, 2021
• Last Update Submitted That Met QC Criteria: July 26, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Nutrition; Parenteral; Abdominal surgery; SmofKabiven
• Other Study ID Numbers: SMKV-015-CP3

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