Ursodiol for Treating Parenteral Nutrition Associated Cholestasis in Neonates

Cholestasis Clinical Trial

— URSONEONAT  

Official title:

Ursodiol for Treating Parenteral Nutrition Associated Cholestasis in Neonates

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00846963
• Other study ID #: RC:127
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: February 17, 2009
• Last updated: September 16, 2013
• Start date: October 2008
• Est. completion date: March 2013

Study information

• Verified date: September 2013
• Source: St. Justine's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether ursodiol is effective in the treatment of parenteral nutrition associated cholestasis in neonates.

Description:

This is the first randomised controlled study that address the question of the role of ursodiol as treatment of cases of PNAC.

It includes all neonates with stratification of less than and equal to 32 weeks or more than 32 weeks of gestation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: March 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Preterm or in-term newborns hospitalized in neonatal care units at CHU Sainte-Justine between October 1st 2008 and October 1st 2011.

• Must be receiving parenteral nutrition (either partial or total) at the diagnosis of cholestasis.

• Parental Consent must be obtained.

Exclusion Criteria:

• Active urinary tract infection

• Presence of clinical signs(acholic stool) of or ultrasound evidence of biliary tract anomalies.

• Positive TORCH infections(Toxoplasmosis, Other infections, Rubella, Cytomegalovirus, Herpes simplex virus)

• Known short bowel syndrome

• Known congenital hypothyroidism

• Known genetic disorders associated with cholestasis like galactosemia, phenylcytonuria, antitrypsin 1 deficiency... etc

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cholestasis

Intervention

Drug:
• Ursodiol
Ursodiol is given by mouth, three times a day from second value of elevated conjugated bilirubin (>33mmol/L) to the resolution of cholestasis (conjugated bilirubin <34mmol/L) If Nil per os, 3,3mg/kg/dose is given. If Nil per os is required (e.g. pre-surgery, or necrotizing enterocolitis), none is given. If enteral feeding is under 100mL/kg/day, 6,7 mg/kg/day is given. If enteral feeding exceeds 100mL/kg/day, 10 mg/kg/day is given.
• placebo
Placebo given in the same amount that ursodiol would be given, depending on enteral feeding and weight. It is also given three times a day, until cholestasis resolution.

Locations

Country	Name	City	State
Canada	CHU Sainte-Justine	Montréal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Ibrahim Mohamed

Country where clinical trial is conducted

Canada, 

References & Publications (5)

Al-Hathlol K, Al-Madani A, Al-Saif S, Abulaimoun B, Al-Tawil K, El-Demerdash A. Ursodeoxycholic acid therapy for intractable total parenteral nutrition-associated cholestasis in surgical very low birth weight infants. Singapore Med J. 2006 Feb;47(2):147-51. — View Citation

Arslanoglu S, Moro GE, Tauschel HD, Boehm G. Ursodeoxycholic acid treatment in preterm infants: a pilot study for the prevention of cholestasis associated with total parenteral nutrition. J Pediatr Gastroenterol Nutr. 2008 Feb;46(2):228-31. doi: 10.1097/MPG.0b013e3181560524. — View Citation

Chen CY, Tsao PN, Chen HL, Chou HC, Hsieh WS, Chang MH. Ursodeoxycholic acid (UDCA) therapy in very-low-birth-weight infants with parenteral nutrition-associated cholestasis. J Pediatr. 2004 Sep;145(3):317-21. — View Citation

McKiernan PJ. Neonatal cholestasis. Semin Neonatol. 2002 Apr;7(2):153-65. Review. — View Citation

Venigalla S, Gourley GR. Neonatal cholestasis. Semin Perinatol. 2004 Oct;28(5):348-55. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Length of parenteral nutrition associated cholestasis (in days)		at the end of cholestasis (when conjugated bilirubin < 34 mmol/L) average of 4 weeks.	No
Secondary	Peak value of biomarkers associated with cholestasis (Gamma-glutamyl transpeptidase, Alkaline phosphatase, conjugated bilirubin)		at least once a week, during cholestasis	No
Secondary	1- Other hepatic marker (Aspartate transaminase, alanine transaminase, albumin blood level)		at least once a week, during cholestasis	No
Secondary	Length required to minimal enteral feeding (120mL/kg/day) measured in days.		From birth to outcome (usually less than 21 days)	No
Secondary	Weight gain (in g/kg/day)		From birth to resolution of cholestasis (very varuiable but usually less than 3 months)	No
Secondary	Adverse effects linked to ursodiol		From beginning to the end of the medication (average 4 weeks)	Yes