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

Official title

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

Overview

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.

Interventions

• Drug SMOFlipid® (lipid injectable emulsion)
  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 nutri

Primary outcome measures

• Incidence of PNAC [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 (12)

• Laboratory values: triglycerides [Time frame: 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 [Time frame: 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 [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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).]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

United States · 5 centers

• Emory University Hospital — Atlanta
• The University of Chicago — Chicago
• Riley Hospital for Children — Indianapolis
• Nationwide Children's Hospital — Columbus
• Children's Hospital of Pittsburgh of UPMC — Pittsburgh

Identifiers

NCT: NCT06049680 · SMOF-044-CP4 (PMR 4240-1)

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗