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.

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).

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.