NCT02633384

Incidence and Severity of Parenteral Nutrition Associated Cholestasis in Neonates Subjected to Major Surgery, Using Two Mixed Intravenous Lipid Emulsions

Terminated Phase 4 Last updated 11 July 2017

What this trial tests

Phase 4 trial testing SMOFlipid in Intrahepatic, Cholestasis in 52 participants. Terminated before completion.

Timeline

1 August 2011

Primary endpoint
1 July 2015

1 April 2017

Quick facts

Lead sponsor	Centro Hospitalar de Lisboa Central
Phase	Phase 4
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	prevention
Enrollment	52
Start date	1 August 2011
Primary completion	1 July 2015
Estimated completion	1 April 2017

Drugs / interventions tested

• SMOFlipid — full drug profile →
• Lipofundin — full drug profile →

Conditions studied

• Intrahepatic, Cholestasis — all drugs for Intrahepatic, Cholestasis →

Sponsor

Centro Hospitalar de Lisboa Central

Who can join

Adults 12 Hours to 48 Hours, any sex, with Intrahepatic, Cholestasis. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Incidence of cholestasis
  Time frame: From recruitment to full enteral feeding per mouth (up to 90 postnatal days)
  Conjugated serum bilirubin \>1 mg/dl (34 mmol/L) (Moyer, 2004).

Sponsor's own description

Parenteral nutrition associated cholestasis (PNAC) is a common complication of prolonged and exclusive parenteral nutrition (PN). Infants subjected to major surgery are often unable to receive enteral nutrition for a long period of time, during which they require exclusive PN. In preterm infants, hepatic immaturity is a predisposing factor. Intravenous lipid emulsions (ILE) used in PN may promote PNAC or protect against it depending on their composition. Medium chain triglycerides (MCT) may have a hepatic protective effect. Long chain triglycerides (LCT) of n-3 family may protect from PNAC. In several new-generation emulsions, the α-tocopherol content is higher than the gamma-tocopherol content, acting as an antioxidant, preventing lipid peroxidation.

The incidence and severity of PNAC in term and near-term infants subjected to corrective surgery for congenital abnormalities and needing prolonged PN using the ILE SMOFlipid® or Lipofundin® is compared. The investigators hypothesise that SMOFlipid® is more protective from PNAC than Lipofundin®.

Single-center, randomized, controlled and double-blinded trial on consecutive neonates admitted in the NICU, with gestational age of 34 weeks or over, undergoing corrective surgery of congenital anomaly of the digestive tract or indirectly affecting the digestive tract. Recruitment if PN with ILE was started within the first 48 hours after birth. Minimum intervention: exclusive PN for at least 1 week.

Main outcome: incidence of cholestasis (conjugated serum bilirubin \>1 mg/dl \[34 mmol/L\]). Severity of cholestasis evaluated by the magnitude of the serum conjugated bilirubin and serum γ-glutamyltranspeptidase (GGT). Mixed effects regression models are used to take into account the correlation structure between measures in time. Crude and adjusted odds-ratios with corresponding 95% confidence intervals are calculated.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Parenteral nutrition-associated cholestasis and triglyceridemia in surgical term and near-term neonates: A pilot randomized controlled trial of two mixed intravenous lipid emulsions.
   Pereira-da-Silva L, Pereira-da-Silva L, Nóbrega S, Rosa ML, et al · · 2017 · cited 19× · PMID 29415837 · DOI 10.1016/j.clnesp.2017.08.007
2. Lipid emulsions for parenterally fed term and late preterm infants.
   Kapoor V, Malviya MN, Soll R. · · 2019 · cited 16× · PMID 31158920 · DOI 10.1002/14651858.cd013171.pub2