Clinical trial NCT03792087: Efficacy and Safety of SmofKabiven Peripheral Versus Compounded Emulsion
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parenteral Feeding
Surgery
Keywords: SmofKabiven
Nutrition
Parenteral
Abdominal surgery
Lead sponsor: Fresenius Kabi
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2019-01-03
Enrollment: 272
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Serum Prealbumin
timeFrame: 6 days
Secondary outcomes:
measure: C-reactive Protein (CRP)
timeFrame: 6 days
measure: Linoleic acid
timeFrame: 6 days
measure: Linolenic acid
timeFrame: 6 days
measure: Arachidonic acid
timeFrame: 6 days
measure: Eicosapentaenoic acid (EPA)
timeFrame: 6 days
measure: Docosahexaenoic acis (DHA)
timeFrame: 6 days
measure: Thromboxane B3 (TXB3)
timeFrame: 6 days
measure: Thromboxane B2 (TXB2)
timeFrame: 6 days
measure: Interleukin (IL)-1
timeFrame: 6 days
measure: IL-2
timeFrame: 6 days
measure: IL-6
timeFrame: 6 days
measure: Cluster of Differentiation 4 (CD4) /Cluster of Differentiation 8 (CD8)
timeFrame: 6 days
measure: Plasma amino acid (taurine)
timeFrame: 6 days
Other outcomes:
measure: Adverse Events (AE)
timeFrame: up to 16 days
measure: Local intolerance for peripherally infusion
timeFrame: 6 days
measure: Development of phlebitis
timeFrame: 6 days
measure: Development of thrombophlebitis
timeFrame: 6 days
measure: Blood pressure
timeFrame: up to 16 days
measure: Heart rate
timeFrame: up to 16 days
measure: Respiratory rate
timeFrame: up to 16 days
measure: Body temperature
timeFrame: up to 16 days
measure: Physical examination
timeFrame: up to 16 days
measure: Red blood cell (RBC) count
timeFrame: up to 16 days
measure: Total white blood cell (WBC) count
timeFrame: up to 16 days
measure: Haemoglobin (Hb)
timeFrame: up to 16 days
measure: Haematocrit (Hct)
timeFrame: up to 16 days
measure: Platelets
timeFrame: up to 16 days
measure: Creatinine
timeFrame: up to 16 days
measure: Urea
timeFrame: up to 16 days
measure: Sodium
timeFrame: up to 16 days
measure: Potassium
timeFrame: up to 16 days
measure: Magnesium
timeFrame: up to 16 days
measure: Total calcium
timeFrame: up to 16 days
measure: Chloride
timeFrame: up to 16 days
measure: Phosphate
timeFrame: up to 16 days
measure: Aspartate aminotransferase (AST)
timeFrame: up to 16 days
measure: Alanine aminotransferase (ALT)
timeFrame: up to 16 days
measure: Alkaline phosphatase (AP)
timeFrame: up to 16 days
measure: Gamma-glutamyl transpeptidase (γ-GT)
timeFrame: up to 16 days
measure: Lactate dehydrogenase (LDH)
timeFrame: up to 16 days
measure: Total and direct bilirubin
timeFrame: up to 16 days
measure: Albumin
timeFrame: up to 16 days
measure: Total protein
timeFrame: up to 16 days
measure: Glucose
timeFrame: up to 16 days
measure: Cholesterol
timeFrame: up to 16 days
measure: Triglycerides
timeFrame: up to 16 days
measure: Low Density Lipoprotein (LDL)-C
timeFrame: up to 16 days
measure: High Density Lipoprotein (HDL)-C
timeFrame: up to 16 days
measure: Fibrinogen
timeFrame: up to 16 days
measure: Activated partial thromboplastin time (APTT)
timeFrame: up to 16 days
measure: Prothrombin time (PT)
timeFrame: up to 16 days
measure: International Normalised Ratio (INR)
timeFrame: up to 16 days
measure: power of hydrogen (pH) value
timeFrame: up to 16 days
measure: Bilirubin
timeFrame: up to 16 days
measure: Protein
timeFrame: up to 16 days
measure: WBC
timeFrame: up to 16 days
measure: RBC
timeFrame: up to 16 days
measure: Urine Glucose
timeFrame: up to 16 days
measure: Ketone body
timeFrame: up to 16 days
measure: ECG
timeFrame: up to 16 days
measure: Preparation time
timeFrame: 5 days
Locations:
city: Beijing
country: China
facility: Beijing Friendship Hospital Capital Medical University
city: Beijing
country: China
facility: Peking University People's Hospital
city: Nanjing
country: China
facility: The First Affiliated Hospital with Nanjing Medical University
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
Study officials:
affiliation: Fudan University
name: Wu Guohao, MD
role: PRINCIPAL_INVESTIGATOR
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