Clinical trial NCT03792100: Efficacy & Safety of SmofKabiven Emulsion for Infusion vs Hospital Compounded "All in One" for Parenteral Nutrition
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parenteral Nutrition
Surgery
Keywords: SmofKabiven
Abdominal surgery
Parenteral
Nutrition
Lead sponsor: Fresenius Kabi
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2019-01-03
Enrollment: 273
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
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, 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.

Detailed description: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Serum Prealbumin
timeFrame: 6 days
Secondary outcomes:
measure: Nosocomial infection
timeFrame: 6 days
measure: Prealbumin
timeFrame: 4 days
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 (TX B3) / Thromboxane B2 (TX B2)
timeFrame: 6 days
measure: Interleukin (IL)-1
timeFrame: 6 days
measure: Interleukin (IL)-2
timeFrame: 6 days
measure: Interleukin (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: Blood pressure
timeFrame: up to 16 days
measure: Heart rate
timeFrame: up to 16 days
measure: Respiratory rate
timeFrame: up to 16 days
measure: Axillary 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 water (pH) value
timeFrame: up to 16 days
measure: Bilirubin
timeFrame: up to 16 days
measure: Protein
timeFrame: up to 16 days
measure: White Blood Cell (WBC)
timeFrame: up to 16 days
measure: Red Blood Cell (RBC)
timeFrame: up to 16 days
measure: Urine Glucose
timeFrame: up to 16 days
measure: Ketone body
timeFrame: up to 16 days
measure: Electrocardiogram (ECG)
timeFrame: up to 16 days
Locations:
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
city: Changchun
country: China
facility: The Second Hospital of Jilin University
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
city: Nanning
country: China
facility: Thepeople's hospital of Guangxi zhuang
city: Shanghai
country: China
facility: Shanghai First People's hospital
city: Shanghai
country: China
facility: Shanghai Pudong Hospital
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
city: Taiyuan
country: China
facility: Shanxi Provincial People's Hospital
Study officials:
affiliation: Beijing Friendship Hospital
name: Zhang Zhongtao, MD
role: PRINCIPAL_INVESTIGATOR
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