Efficacy and Safety of SmofKabiven Peripheral Versus Compounded Emulsion

Surgery Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03792087
• Other study ID #: SMKV-011-CP3
• Status: Completed
• Phase: Phase 3
• Start date: December 21, 2017
• Est. completion date: December 30, 2018

Study information

• Verified date: July 2021
• Source: Fresenius Kabi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 272
• Est. completion date: December 30, 2018
• Est. primary completion date: December 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Parenteral Feeding
• Surgery

Intervention

Drug:
• SmofKabiven Peripheral
Total Parenteral Nutrition
• Hospital compounded emulsion
Total Parenteral Nutrition

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Fresenius Kabi	Parexel

Country where clinical trial is conducted

China, 

References & Publications (25)

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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. — View Citation

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Fresenius Kabi. SomfKabiven Peripheral, emulsion for infusion. Summary of Product Characteristics, dated September.29. 2009

Grimm H, Mertes N, Goeters C, Schlotzer E, Mayer K, Grimminger F, Fürst P. Improved fatty acid and leukotriene pattern with a novel lipid emulsion in surgical patients. Eur J Nutr. 2006 Feb;45(1):55-60. Epub 2005 Jul 22. — View Citation

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. — View Citation

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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. Epub 2003 Feb 25. — View Citation

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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. — View Citation

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Shenkin A. Serum prealbumin: Is it a marker of nutritional status or of risk of malnutrition? Clin Chem. 2006 Dec;52(12):2177-9. — View Citation

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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. — View Citation

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* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse Events (AE)	Coded according to Medical Dictionary for Regulatory Affairs (MedDRA) by System Organ Class (SOC) and preferred term	up to 16 days
Other	Local intolerance for peripherally infusion	Reported as AE	6 days
Other	Development of phlebitis	Reported as AE	6 days
Other	Development of thrombophlebitis	Reported as AE	6 days
Other	Blood pressure	Vital signs	up to 16 days
Other	Heart rate	Vital signs	up to 16 days
Other	Respiratory rate	Vital signs	up to 16 days
Other	Body temperature	Vital signs	up to 16 days
Other	Physical examination	Examination of abnormal findings in any system/organ	up to 16 days
Other	Red blood cell (RBC) count	Laboratory variables	up to 16 days
Other	Total white blood cell (WBC) count	Laboratory variables	up to 16 days
Other	Haemoglobin (Hb)	Laboratory variables	up to 16 days
Other	Haematocrit (Hct)	Laboratory variables	up to 16 days
Other	Platelets	Laboratory variables	up to 16 days
Other	Creatinine	Laboratory variables	up to 16 days
Other	Urea	Laboratory variables	up to 16 days
Other	Sodium	Laboratory variables	up to 16 days
Other	Potassium	Laboratory variables	up to 16 days
Other	Magnesium	Laboratory variables	up to 16 days
Other	Total calcium	Laboratory variables	up to 16 days
Other	Chloride	Laboratory variables	up to 16 days
Other	Phosphate	Laboratory variables	up to 16 days
Other	Aspartate aminotransferase (AST)	Laboratory variables	up to 16 days
Other	Alanine aminotransferase (ALT)	Laboratory variables	up to 16 days
Other	Alkaline phosphatase (AP)	Laboratory variables	up to 16 days
Other	Gamma-glutamyl transpeptidase (?-GT)	Laboratory variables	up to 16 days
Other	Lactate dehydrogenase (LDH)	Laboratory variables	up to 16 days
Other	Total and direct bilirubin	Laboratory variables	up to 16 days
Other	Albumin	Laboratory variables	up to 16 days
Other	Total protein	Laboratory variables	up to 16 days
Other	Glucose	Laboratory variables	up to 16 days
Other	Cholesterol	Laboratory variables	up to 16 days
Other	Triglycerides	Laboratory variables	up to 16 days
Other	Low Density Lipoprotein (LDL)-C	Laboratory variables	up to 16 days
Other	High Density Lipoprotein (HDL)-C	Laboratory variables	up to 16 days
Other	Fibrinogen	Laboratory variables	up to 16 days
Other	Activated partial thromboplastin time (APTT)	Laboratory variables	up to 16 days
Other	Prothrombin time (PT)	Laboratory variables	up to 16 days
Other	International Normalised Ratio (INR)	Laboratory variables	up to 16 days
Other	power of hydrogen (pH) value	Urine analysis	up to 16 days
Other	Bilirubin	Urine analysis	up to 16 days
Other	Protein	Urine analysis	up to 16 days
Other	WBC	Urine analysis	up to 16 days
Other	RBC	Urine analysis	up to 16 days
Other	Urine Glucose	Urine analysis	up to 16 days
Other	Ketone body	Urine analysis	up to 16 days
Other	ECG	Electrocardiogram to assess cardiac disorders (e.g. Myocardial infarction, Pericarditis, QT interval Prolongation, etc.)	up to 16 days
Other	Preparation time	Comparison of the time required for TPN preparation for the two groups	5 days
Primary	Serum Prealbumin	Change in Serum Prealbumin	6 days
Secondary	C-reactive Protein (CRP)	Change in CRP	6 days
Secondary	Linoleic acid	Change in linoleic acid	6 days
Secondary	Linolenic acid	Change in linolenic acid	6 days
Secondary	Arachidonic acid	Change in arachidonic acid	6 days
Secondary	Eicosapentaenoic acid (EPA)	Change in EPA	6 days
Secondary	Docosahexaenoic acis (DHA)	Change in DHA	6 days
Secondary	Thromboxane B3 (TXB3)	Change in TXB3	6 days
Secondary	Thromboxane B2 (TXB2)	Change in TXB2	6 days
Secondary	Interleukin (IL)-1	Change in IL-1	6 days
Secondary	IL-2	Change in IL-2	6 days
Secondary	IL-6	Change in IL-6	6 days
Secondary	Cluster of Differentiation 4 (CD4) /Cluster of Differentiation 8 (CD8)	Change in CD4/CD8	6 days
Secondary	Plasma amino acid (taurine)	Change in plasma amino acid (taurine)	6 days

External Links

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