Efficacy and Safety of SmofKabiven Peripheral Versus Compounded Emulsion

Efficacy & Safety of SmofKabiven Peripheral vs Compounded Emulsion: A Randomized, Active-Controlled, Open-Labelled, Multi-Centre Study in Adult Surgical Patients Requiring Parenteral Nutrition

The present protocol describes a randomized, open-labelled study in which either SmofKabiven Peripheral or a hospital compounded control Parenteral Nutrition (PN) 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 absolute 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 Feeding
• Intervention / Treatment: Drug: SmofKabiven Peripheral; Drug: Hospital compounded emulsion

Detailed Description

In addition, other variables will be assessed in this study, i.e., C-reactive Protein (CRP), free fatty acids, immunology parameters, taurine, comparison of the time required for Total Parenteral Nutrition (TPN) preparation of the two groups, 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 Peripheral is not inferior to the comparative drug (compounded emulsion).

• Study Type: Interventional
• Enrollment (Actual): 272
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Peking University People's Hospital
  • Beijing, China
    • Beijing Friendship Hospital Capital Medical University
  • Nanjing, China
    • The First Affiliated Hospital with Nanjing Medical University
  • Qingdao, China
    • The Affiliated Hospital of Qingdao University
  • Shanghai, China
    • Zhongshan Hospital, Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient is scheduled to undergo elective abdominal surgery
2. Female or male patient, age between 18 and 75 years (inclusively)
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 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. Severe liver insufficiency or AST, ALT 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, 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. Inborn abnormality of amino acid metabolism
8. Present signs of acute pancreatitis, hypothyroidism or hyper-thyroidism as diagnosed clinically
9. Serum level of any of the electrolytes (sodium, potassium, magnesium, total calcium, chloride, phosphate) above the upper limit of the normal range
10. Known unstable metabolism (e.g., known metabolic acidosis)
11. Known hypersensitivity to fish-, egg-, soybean, or peanut protein or to any of the active substances or excipients of the study drugs
12. General contraindications to infusion therapy: acute pulmonary oedema, hyperhydration, and decompensated cardiac insufficiency /congestive heart failure
13. Unstable conditions (e.g., acute myocardial infarction, stroke, embolism, severe sepsis, shock)
14. Drug abuse and/or chronic alcoholism
15. Psychiatric diseases, epilepsy
16. Administration of growth hormones within the previous 4 weeks before surgery, or chronic maintenance therapy with systemic glucocorticoids 4 weeks before surgery
17. 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
18. Patient is pregnant or lactating and intends to continue breast-feeding

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

    1. Intra-operative blood loss > 1000ml;
    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 haemo-filtration or dialysis;
    5. Contraindication or inability to obtain peripheral or 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
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SmofKabiven Peripheral; Continuous intravenous Infusion for SmofKabiven Peripheral via peripheral or central venous access for 14-24 hours/day. Target dose 34.3 ml per kg body weight/day. Duration of treatment 5 consecutive days.	Drug: SmofKabiven Peripheral; Total Parenteral Nutrition; Other Names: Investigational Product; Study intervention
ACTIVE_COMPARATOR: Hospital compounded emulsion; Continuous intravenous Infusion for Hospital compounded emulsion via peripheral or central venous access for 14-24 hours/day. Target dose 34.3 ml per kg body weight/day. Duration of treatment 5 consecutive days.	Drug: Hospital compounded 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
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
Interleukin (IL)-1	Change in IL-1	6 days
Thromboxane B3 (TXB3)	Change in TXB3	6 days
Thromboxane B2 (TXB2)	Change in TXB2	6 days
IL-2	Change in IL-2	6 days
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 plasma amino acid (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
Physical examination	Examination of abnormal findings in any system/organ	up to 16 days
Bilirubin	Urine analysis	up to 16 days
Protein	Urine analysis	up to 16 days
Urine Glucose	Urine analysis	up to 16 days
Ketone body	Urine analysis	up to 16 days
Local intolerance for peripherally infusion	Reported as AE	6 days
Development of phlebitis	Reported as AE	6 days
Development of thrombophlebitis	Reported as AE	6 days
Body temperature	Vital signs	up to 16 days
Red blood cell (RBC) count	Laboratory variables	up to 16 days
Total white blood cell (WBC) count	Laboratory variables	up to 16 days
Haemoglobin (Hb)	Laboratory variables	up to 16 days
Haematocrit (Hct)	Laboratory variables	up to 16 days
Platelets	Laboratory variables	up to 16 days
Creatinine	Laboratory variables	up to 16 days
Urea	Laboratory variables	up to 16 days
Sodium	Laboratory variables	up to 16 days
Potassium	Laboratory variables	up to 16 days
Magnesium	Laboratory variables	up to 16 days
Total calcium	Laboratory variables	up to 16 days
Chloride	Laboratory variables	up to 16 days
Phosphate	Laboratory variables	up to 16 days
Aspartate aminotransferase (AST)	Laboratory variables	up to 16 days
Alanine aminotransferase (ALT)	Laboratory variables	up to 16 days
Alkaline phosphatase (AP)	Laboratory variables	up to 16 days
Gamma-glutamyl transpeptidase (γ-GT)	Laboratory variables	up to 16 days
Lactate dehydrogenase (LDH)	Laboratory variables	up to 16 days
Total and direct bilirubin	Laboratory variables	up to 16 days
Albumin	Laboratory variables	up to 16 days
Total protein	Laboratory variables	up to 16 days
Glucose	Laboratory variables	up to 16 days
Cholesterol	Laboratory variables	up to 16 days
Triglycerides	Laboratory variables	up to 16 days
Low Density Lipoprotein (LDL)-C	Laboratory variables	up to 16 days
High Density Lipoprotein (HDL)-C	Laboratory variables	up to 16 days
Fibrinogen	Laboratory variables	up to 16 days
Activated partial thromboplastin time (APTT)	Laboratory variables	up to 16 days
Prothrombin time (PT)	Laboratory variables	up to 16 days
International Normalised Ratio (INR)	Laboratory variables	up to 16 days
power of hydrogen (pH) value	Urine analysis	up to 16 days
WBC	Urine analysis	up to 16 days
RBC	Urine analysis	up to 16 days
ECG	Electrocardiogram to assess cardiac disorders (e.g. Myocardial infarction, Pericarditis, QT interval Prolongation, etc.)	up to 16 days
Preparation time	Comparison of the time required for TPN preparation for the two groups	5 days

Collaborators and Investigators

• Sponsor: Fresenius Kabi
• Collaborators: Parexel
• Investigators: Principal Investigator: Wu Guohao, MD, Fudan University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• SSPC. Intralipid 20%, Summary of Product Characteristics, dated 14 February 2007
• SSPC. Novamin 11.4%, Summary of Product Characteristics, dated 01 December 2013
• 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.
• 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 Peripheral, emulsion for infusion. Summary of Product Characteristics, dated September.29. 2009

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): December 21, 2017
• Primary Completion (ACTUAL): December 30, 2018
• Study Completion (ACTUAL): December 30, 2018

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-011-CP3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No