Omegaven investigator-initiated trial

JRCT ID: jRCT2021230032

Registered date:07/11/2023

Basic Information

• Recruitment status: Recruiting

Health condition(s) or Problem(s) studied

Parenteral nutrition associated cholestasis
Intestinal failure associated liver disease

• Date of first enrollment: 01/11/2023
• Target sample size: 20
• Study type: Interventional
• Intervention(s): Continuous intravenous infusion 1g/kg/day of the investigational drug over 10 hours

Outcome(s)

• Primary Outcome: T/T Ratio (Triene/Tetraene Ratio) at Day 56 following the initiation of investigational drug administration.

Secondary Outcome

1.T/T Ratio (Triene/Tetraene Ratio) at multiple time points post-initiation of investigational drug administration (whole cohort & individual)
2.EPA/AA Ratio at multiple time points post-initiation of investigational drug administration (whole cohort & individual)
3.Mead Acid levels at multiple time points post-initiation of investigational drug administration (whole cohort & individual)
4.Improvement and severity trends in liver dysfunction*
4.1 Presence or absence of liver dysfunction improvement at the endpoint of drug administration, including termination
4.2 Severity of liver dysfunction at multiple time points
5.Growth and developmental abnormalities** (weight, height, head circumference) (whole cohort & individual)
6.Proportion of cases with a T/T Ratio of 0.2 or higher at Day 56 post-initiation of investigational drug administration
7.Background information on cases with a T/T Ratio of 0.2 or higher at Day 56 post-initiation of investigational drug administration
* Liver dysfunction assessment includes the following: Duration until d-Bil reaches 1 or 2 mg/dL or lower, duration until AST
and ALT are less than three times the upper limit of normal, trends in liver dysfunction severity (t-Bil, d-Bil, APRI score (every
4 weeks), PELD score (every 4 weeks)), number of cases that developed severe liver conditions such as thrombocytopenia,
gastrointestinal bleeding, ascites accumulation, coagulation disorders, and number of cases leading to death or liver transplantation.
** The assessment of growth and development is based on deviation from the standard (z-score), evaluating the presence and extent of catch-up to standard growth and developmental milestones.

Key inclusion & exclusion criteria

• Age minimum: >=
• Age maximum: < 15age old
• Gender: Both

Include criteria

1. Male and female children under the age of 15 at the time of obtaining consent.
2. Patients for whom written consent has been obtained from a legally authorized representative. For patients aged 6 or older, it is preferable to obtain written consent from the patient themselves after explanation via an assent document, in addition to consent from the legally authorized representative. Verbal consent is acceptable if obtaining written consent from the patient is challenging due to physical conditions. In cases where obtaining either written or verbal consent from the patient is difficult, written consent from the legally authorized representative alone is sufficient.
3. Patients with pediatric intestinal failure (short bowel syndrome, functional intestinal failure, or due to other conditions) who are expected to require parenteral nutrition for more than 6 weeks (42 days), and who meet either or both of the following criteria for intestinal failure-associated liver disease:
Either AST or ALT levels are more than three times the upper limit of the normal range.
Presence of parenteral nutrition-associated cholestasis with a d-Bil level greater than 1 mg/dL.

Exclude criteria

1.Patients diagnosed with or strongly suspected to have comorbidities that may cause liver disease with cholestasis other than intestinal failure and parenteral nutrition, such as viral hepatitis,biliary atresia, primary biliary cholestasis, or lipid metabolism disorders.
2.Patients who have irreversible advanced liver dysfunction or liver failure, meeting any of the following criteria:
Severe jaundice (serum t-Bil >= 15 mg/dL)
Signs of portal hypertension:
Hypersplenism: a spleen-to-left kidney ratio of 1.35 or greater with accompanying thrombocytopenia (=< 30,000/mm3) or
leukopenia (=< 500/mm3)
Gastrointestinal variceal bleeding
Uncontrollable ascites despite diuretics
Severe uncorrectable coagulation disorders(PT-INR >= 1.6)
Hepatic encephalopathy grade III or above with hyperammonemia (>= 100 ug/dL)
3.Patients with severe chromosomal abnormalities (e.g., Trisomy 13, Trisomy 17), or complicated by respiratory failure, heart failure, or renal failure, where the trial's safety or reliable assessment is deemed challenging by the Principal Investigator or Co-investigator.
4.Patients scheduled to undergo surgery unrelated to the trial treatment within 56 days after enrollment.
5.Patients with a known hypersensitivity (allergy) to parenteral lipid emulsions like Omegaven(registered trademark) or its ingredients.
6.Patients who have not passed 28 days since the completion of participation in another clinical trial or interventional study.
7.Patients who have received Omegaven(registered trademark) or other agents, supplements, or enteral nutrition products aimed at supplementing or enhancing n-3 fatty acids within 28 days prior to obtaining consent, and who cannot undergo a washout period of at least 28 days (or 14 days for patients under 1 year of age) after consent. However, administration of already approved (soy-derived) lipid emulsions in Japan is not a concern.
8.Any other patients deemed ineligible by the Principal Investigator or Co-investigator.

Related Information

• Primary Sponsor: Wada Motoshi
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development