Ursodiol for Treating Parenteral Nutrition Associated Cholestasis in Neonates - Full Text View

Sponsor:	St. Justine's Hospital
Information provided by:	St. Justine's Hospital
ClinicalTrials.gov Identifier:	NCT00846963

Purpose

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

Condition	Intervention	Phase
Cholestasis	Drug: Ursodiol Drug: placebo	Phase II Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Ursodiol for Treating Parenteral Nutrition Associated Cholestasis in Neonates

Resource links provided by NLM:

Drug Information available for: Ursodeoxycholic acid

U.S. FDA Resources

Further study details as provided by St. Justine's Hospital:

Primary Outcome Measures:

Length of parenteral nutrition associated cholestasis (in days) [ Time Frame: at the end of cholestasis (when conjugated bilirubin < 34 mmol/L) average of 4 weeks. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Peak value of biomarkers associated with cholestasis (Gamma-glutamyl transpeptidase, Alkaline phosphatase, conjugated bilirubin) [ Time Frame: at least once a week, during cholestasis ] [ Designated as safety issue: No ]
1- Other hepatic marker (Aspartate transaminase, alanine transaminase, albumin blood level) [ Time Frame: at least once a week, during cholestasis ] [ Designated as safety issue: No ]
Length required to minimal enteral feeding (120mL/kg/day) measured in days. [ Time Frame: From birth to outcome (usually less than 21 days) ] [ Designated as safety issue: No ]
Weight gain (in g/kg/day) [ Time Frame: From birth to resolution of cholestasis (very varuiable but usually less than 3 months) ] [ Designated as safety issue: No ]
Adverse effects linked to ursodiol [ Time Frame: From beginning to the end of the medication (average 4 weeks) ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	50
Study Start Date:	October 2008
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	October 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Ursodiol Participants assigned in this arm receive an ursodiol suspension at 20mg/ml.	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. Other Names: Urso ursodeoxycholic acid ursodiol
Placebo Comparator: placebo A placebo suspension that looks like the ursodiol suspension used.	Drug: 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. Other Name: placebo

Arms

Assigned Interventions

Experimental: Ursodiol

Participants assigned in this arm receive an ursodiol suspension at 20mg/ml.

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.

Other Names:

Urso
ursodeoxycholic acid
ursodiol

Placebo Comparator: placebo

A placebo suspension that looks like the ursodiol suspension used.

Drug: 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.

Other Name: placebo

Detailed 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.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00846963

Contacts

Contact: Ibrahim Mohamed, MB ChB, DIS P(Fr)	514-345-4931 ext 4441	ibrahim.mohamed.hsj@ssss.gouv.qc.ca
Contact: Josianne Malo, B.Pharm, M.Sc.	514-345-4931 ext 6290	Josianne_Malo@ssss.gouv.qc.ca

Locations

Canada, Quebec
CHU Sainte-Justine	Recruiting
Montréal, Quebec, Canada, H3T 1C5
Contact: Ibrahim Mohamed ibrahim.mohamed.hsj@ssss.gouv.qc.ca
Principal Investigator: Ibrahim Mohamed, MB ChB, DIS Ped, Fellowship
Sub-Investigator: Josianne Malo, B.Pharm, M.Sc
Sub-Investigator: Jessica McMahon, B.Pharm
Sub-Investigator: Maxime Thibault, B.Pharm
Sub-Investigator: Guillaume Faubert, B.Pharm
Sub-Investigator: Julie Charbonneau, B.Pharm
Sub-Investigator: Ema Ferreira, B.Pharm, M.Sc, Pharm.D
Sub-Investigator: Denis Lebel, B.Pharm, M.Sc
Sub-Investigator: Jean-François Bussières, B.Pharm, M.Sc, MBA, FSCHP
Sub-Investigator: Valérie Marchand, MD, FRCPC

Sponsors and Collaborators

St. Justine's Hospital

Investigators

Principal Investigator:	Ibrahim Mohamed, MB ChB, DIS P	St. Justine's Hospital
Study Director:	Josianne Malo, B.Pharm, M.Sc.	St. Justine's Hospital

More Information

Publications:

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.

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.

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.

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

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

Responsible Party:	Ibrahim Mohamed, CHU Sainte-Justine
ClinicalTrials.gov Identifier:	NCT00846963 History of Changes
Other Study ID Numbers:	RC:127
Study First Received:	February 17, 2009
Last Updated:	August 2, 2011
Health Authority:	Canada: Health Canada

Keywords provided by St. Justine's Hospital:

parenteral nutrition associated cholestasis in neonates
parenteral nutrition induced cholestasis in preterms
Bile duct obstruction
biliary stasis

Additional relevant MeSH terms:

Cholestasis
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Ursodeoxycholic Acid

Cholagogues and Choleretics
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012