Hospitalized Neonates and Infants, Expected to Require Parenteral Nutrition for 28 Days Clinical Trial
Official title:
A Prospective, Randomized, Controlled, Double-Blind, Parallel-Group, Phase 3 Study to Compare Safety and Efficacy of Smoflipid 20% to Intralipid 20% in Hospitalized Neonates and Infants Requiring 28 Days of Parenteral Nutrition
| Verified date | December 2021 |
| Source | Fresenius Kabi |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
To show the superiority in safety of Smoflipid over Intralipid® as measured by the number of study patients in each treatment group with conjugated bilirubin exceeding 2 mg/dL during the first 28 days of study treatment, confirmed by a second sample collected 7 days after the first sample.
| Status | Terminated |
| Enrollment | 204 |
| Est. completion date | April 10, 2020 |
| Est. primary completion date | April 3, 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | N/A and older |
| Eligibility | Inclusion Criteria: - Neonates and infants, expected to require parenteral nutrition (PN) for 28 days - Postmenstrual age = 24 weeks - Birth weight = 750g - Gastroschisis, duodenal, jejunal or ileal atresia, volvulus, spontaneous intestinal perforation or necrotizing enterocolitis (Bell's stage 2B or higher) - At least 80% of nutritional needs at baseline received by PN - Signed and dated informed consent obtained from at least one parent or legal guardian Exclusion Criteria: - Conjugated bilirubin > 0.6 mg/dL - Any known pre-, intra- or posthepatic complication increasing conjugated bilirubin levels > 0.6, mg/dL during study participation - Suspected liver disease or liver damage based on either aspartate aminotransferase (AST), alanine aminotransferase (ALT), or gamma-glutamyl transferase (GGT) exceeding 2.5x upper limit of normal range - Active bloodstream infection demonstrated by positive blood culture at screening - Cystic fibrosis - Meconium ileus - Serum triglyceride levels > 250 mg/dL - Cyanotic congenital heart defect - Severe renal failure with serum creatinine > 2.0 mg/dL - History of shock requiring vasopressors - Anasarca - Extracorporeal Membrane Oxygenation (ECMO) - Known inborn errors of metabolism - Known congenital viral infection - Unlikely to survive longer than 28 days - Known hypersensitivity to fish-, egg-, soya- or peanut protein or to any of the active substances or excipients |
| Country | Name | City | State |
|---|---|---|---|
| United States | Ann & Robert H. Lurie Children's Hospital of Chicago | Chicago | Illinois |
| United States | Texas Children's Hospital | Houston | Texas |
| United States | Vanderbilt Children's Hospital | Nashville | Tennessee |
| United States | Yale - New Haven Children's Hospital | New Haven | Connecticut |
| United States | Mount Sinai Hospital | New York | New York |
| United States | Steven & Alexandra Cohen Children's Medical Center of NY | New York | New York |
| United States | The Children's Hospital at OU Medical Center | Oklahoma City | Oklahoma |
| United States | University of Nebraska Medical Center | Omaha | Nebraska |
| United States | Lucile Packard Children's Hospital | Palo Alto | California |
| United States | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania |
| United States | Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania |
| United States | Rady Children's Hospital San Diego | San Diego | California |
| United States | UC San Diego Medical Center | San Diego | California |
| Lead Sponsor | Collaborator |
|---|---|
| Fresenius Kabi |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | The Number of Patients in Each Treatment Group With Conjugated Bilirubin Levels > 2 mg/dL During the First 28 Days of Study Treatment, Confirmed by a Second Sample Collected 7 Days After the First Sample | Analysis of patients with Event at any timepoint of sampling (i.e. Day 8, 15, 22, 29/end of Treatment) and subsequent (i.e. +7 days) confirmation. | Screening, Day 8, 15, 22, 29/end of treatment + confirmatory sample: 7 days after conjugated bilirubin level exceeds 2 mg/dl | |
| Secondary | Body Weight (Change From Baseline) | Data were age-standardized using growth charts as suggested by Fenton (Fenton et al., 2013) and the World Health Organization (WHO) Multicenter Growth Reference Study (MGRS; WHO 2006, 2007). | Day 1-29, and at Follow-up (+7 days) (if continued: until Day 85 + at Follow up) | |
| Secondary | Body Length (Change From Baseline) | Data were age-standardized using growth charts as suggested by Fenton (Fenton et al., 2013) and the World Health Organization (WHO) Multicenter Growth Reference Study (MGRS; WHO 2006, 2007). | Day 1, 8, 15, 22, 29/end of treatment, if continued: Day 36, 43, 50, 57, 64, 71, 78, 85/end of treatment, Follow-up | |
| Secondary | Head Circumference (Change From Baseline) | Data were age-standardized using growth charts as suggested by Fenton (Fenton et al., 2013) and the World Health Organization (WHO) Multicenter Growth Reference Study (MGRS; WHO 2006, 2007). | Day 1, 8, 15, 22, 29/end of treatment, if continued: Day 36, 43, 50, 57, 64, 71, 78, 85/end of treatment, Follow-up | |
| Secondary | Time to Full Enteral or Oral Feeds | Time to full enteral or oral feeds (i.e. PN weaning) is the time from the randomization date to the date of the first full enteral or oral Feeds. | Day 29/end of treatment, if continued: Day 85/end of treatment | |
| Secondary | Fatty Acids in Plasma and Red Blood Cell Membranes (Change From Baseline) | RBC refers to red blood cells. Timepoints >10% of Subjects (overall) are displayed. | Day 1, Day 29/end of treatment, if continued: Day 57, 85/end of treatment | |
| Secondary | Length of Stay in Hospital | Length of stay in hospital (time from randomization to discharge) was be calculated.
NA=Not available |
Day 1- Follow up (7 days after end of treatment) | |
| Secondary | Ratio of Independent Bloodstream Infections to Number of Days on Study Medication | The Ratio is the incidence of bloodstream infection by numbers of day on study medication. | Day 1-29 or -85 if continued + Follow-up | |
| Secondary | Number of Patients With 1 or More Bloodstream Infections to Number of Patients on Study Medication | Day 1-29 or -85 if continued + Follow-up | ||
| Secondary | Number of Patients Who Complete PN Treatment Without Lipid Minimization | The Analysis was conducted over all study phases. | Day 1-29 or -85 if continued + Follow-up | |
| Secondary | Number of Patients Needing to be Withdrawn From the Study Due to Elevated Conjugated Bilirubin Levels | Day 1-29 or -85 if continued + Follow-up | ||
| Secondary | Area Under the Curve for Time Period in Which Conjugated Bilirubin Levels Are > 1.5 mg/dL in Patients Who Are Not Withdrawn From the Study | The area under the curve (AUC>1.5) is defined as the area between conjugated bilirubin concentrations > 1.5 mg/dL and the horizontal line at 1.5 mg/dL, restricted by the time point of study withdrawal, if applicable. Analysis displays the summary of Area Under the Curve of Bilirubin Levels for the Time Period in Which Conjugated are >1.5 mg/dL | Day 1-29 or -85 if continued + Follow-up | |
| Secondary | Cumulative Number of Days Patients Are Administered a Lipid Dose Without Lipid Minimization | The Analysis was performed over the entire study period. | Day 1-29 or -85 if continued + Follow-up | |
| Secondary | Time to Conjugated Bilirubin > 2 mg/dL (Confirmed by a Second Sample Collected 7 Days After the First) | Day 1-29 or -85 if continued + Follow-up | ||
| Secondary | Blood Sampling for Special Analysis (Sterols Including Phytosterols, a-tocopherol) | Day 1, Day 29/end of treatment, if continued: Day 57, 85/end of treatment | ||
| Secondary | Holman Index | Essential fatty acid deficiency is based on the ratio of Mead acid and Arachidonic acid (also called the triene/tetraene ratio or Holman index; Holman, 1960). A ratio of > 0.2 was considered abnormal (=essential fatty acid deficiency; Holman et al., 1979). Timepoints with >10% of patients are displayed. | Day 1, Day 29/end of treatment, if continued: Day 57, 85/end of treatment |