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.

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).

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.