Safety Study of SMOFlipid to Evaluate the Risk of Developing EFAD and/or PNAC in Pediatric and Adult Patients

Study Overview
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Brief Summary
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Evaluate the risk of developing EFAD and/or PNAC in adult and pediatric patients 1 month of age and older, who are anticipated to need 8 weeks or longer of parenteral nutrition treatment with SMOFlipid.

Official Title
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A Single-arm Open-label Safety Study of SMOFlipid to Evaluate the Risk of Developing Essential Fatty Acid Deficiency (EFAD) and/or Parenteral Nutrition-associated Cholestasis (PNAC) in Pediatric Patients 1 Month to 17 Years of Age and in Adult Patients, Who Are Anticipated to Need 8 Weeks or Longer of Parenteral Nutrition Treatment

Conditions
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Malnutrition, Child, Malnutrition

Intervention / Treatment
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* Drug: SMOFlipid® (lipid injectable emulsion)


Participation Criteria
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Eligibility Criteria
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Age Limits: and Adults Inclusion Criteria: Male or female patients, at least 1 month of age. Patients who require PN for at least 5 days/week. Patients who receive 80% or more of their total energy requirements as PN at enrollment and who are expected to receive 80% or more of their total energy requirements as PN for at least 56 days. Written informed consent. In case of pediatric patients, informed consent must be obtained from parent(s) or legal representatives. If possible, the assent of the pediatric patient must also be obtained (according to local law). Exclusion Criteria: Use of any other lipid injectable emulsion than SMOFlipid within 6 months prior to study participation Known hypersensitivity to fish, egg, soybean, or peanut proteins, or to any of the active ingredients or excipients of SMOFlipid. Hyperlipidemia or disorders of lipid metabolism characterized by hypertriglyceridemia (serum triglyceride concentration >250 mg/dL in infants or >400 mg/dL in older pediatric and adult patients). Inborn errors of amino acid metabolism. Cardiopulmonary instability (including pulmonary edema, cardiac insufficiency, myocardial infarction, acidosis and hemodynamic instability requiring significant vasopressor support). Hemophagocytic syndrome. Liver enzymes (either AST, or ALT, or GGT) exceeding 2 x upper limit of normal range Direct bilirubin exceeding 2 x upper limit of normal range INR exceeding 2 x upper limit of normal range and patient not receiving oral anticoagulants. Any known hepatic condition outside of IFALD that will increase direct bilirubin ≥2.0 mg/dL. Clinically significant abnormal levels of any serum electrolyte (sodium, potassium, magnesium, calcium, chloride, phosphate). Active bloodstream infection demonstrated by positive blood culture at screening. Severe renal failure (eGFR <15 ml/min per 1.73 m2) including patients on renal replacement therapy. Abnormal blood pH, oxygen saturation, or carbon dioxide. Pregnancy or lactation. Participation in another interventional clinical study. Unlikely to survive longer than 56 days.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Single arm SMOFlipid® (lipid injectable emulsion)<br>Investigational drug: SMOFlipid® (lipid injectable emulsion). | Drug: SMOFlipid® (lipid injectable emulsion)<br>* SMOFlipid is a sterile, nonpyrogenic, white, homogenous lipid emulsion for intravenous infusion. The lipid content of SMOFlipid is 0.20 g/mL, and comprises a mixture of soybean oil, MCT, olive oil, and fish oil. SMOFlipid belongs to the pharmacotherapeutic group: Solutions for parenteral nutrition, fat emulsions (ATC-code: B05BA02). SMOFlipid is indicated in adult and pediatric patients, including term and preterm neonates, as a source of calories and essential fatty acids for parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of PNAC | defined as direct bilirubin level > 2 mg/dL, confirmed by a second sample collected 7 days after the first sample | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Time to direct bilirubin > 2mg/dL | (confirmed by a second sample collected 7 days after the first) | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Incidence of EFAD | Triene/tetraene ratio in total plasma to assess EFAD (Holman 1960), Severity of EFAD will be graded based on triene/tetraene ratio, as suspected ≥ 0.05, moderate ≥ 0.20 and severe ≥ 0.40 (Cober et al 2012) | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Incidence of clinical EFAD |  | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Fatty acids | analyzed in total plasma, including linoleic acid, α-linolenic acid, arachidonic acid, docosahexaenoic acid, eicosapentaenoic acid and Mead acid | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Laboratory values: triglycerides |  | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Laboratory values: direct bilirubin |  | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Laboratory values: total bilirubin |  | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Laboratory values: alanine aminotransferase (ALT) |  | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Laboratory values: aspartate aminotransferase (AST) |  | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Laboratory values: gamma-glutamyl transferase (GGT) |  | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Laboratory values: alkaline phosphatase (ALP) |  | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Laboratory values: creatinine |  | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Laboratory values: urea nitrogen |  | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Laboratory values: electrolytes |  | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Laboratory values: glucose |  | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Laboratory values: total protein |  | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Laboratory values hematology: white blood cell count (WBC), red blood cell count (RBC), and platelet count |  | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Laboratory values hematology: Hemoglobin |  | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Laboratory values hematology Hematocrit |  | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Laboratory values hematology: International normalized ratio |  | At baseline before start of treatment to assess eligibility | 
| Vital signs: Blood pressure |  | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Vital signs: Heart rate |  | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Vital signs: Body temperature |  | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| Incidence of adverse events |  | Start of Treatment until After End of Last Study PN (+6 months for pediatric patients). Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). | 
| BMI | BMI is the weight in kilograms divided by height in meters squared. Alternatively, BMI can be calculated by dividing the weight in kilograms by the height in centimeters squared, and then multiplying the result by 10,000. | Start of Treatment until After End of Last Study PN Duration of Treatment: Study treatment will last for a minimum of 8 weeks (56 consecutive days) and as long as PN is indicated, up to 1 year (365 consecutive days). |