Ursodiol for Treating Parenteral Nutrition Associated Cholestasis in Neonates (URSONEONAT)
Primary Purpose
Cholestasis
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Ursodiol
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Cholestasis focused on measuring parenteral nutrition associated cholestasis in neonates, parenteral nutrition induced cholestasis in preterms, Bile duct obstruction, biliary stasis
Eligibility 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
Sites / Locations
- CHU Sainte-Justine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Ursodiol
placebo
Arm Description
Participants assigned in this arm receive an ursodiol suspension at 20mg/ml.
A placebo suspension that looks like the ursodiol suspension used.
Outcomes
Primary Outcome Measures
Length of parenteral nutrition associated cholestasis (in days)
Secondary Outcome Measures
Peak value of biomarkers associated with cholestasis (Gamma-glutamyl transpeptidase, Alkaline phosphatase, conjugated bilirubin)
1- Other hepatic marker (Aspartate transaminase, alanine transaminase, albumin blood level)
Length required to minimal enteral feeding (120mL/kg/day) measured in days.
Weight gain (in g/kg/day)
Adverse effects linked to ursodiol
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00846963
Brief Title
Ursodiol for Treating Parenteral Nutrition Associated Cholestasis in Neonates
Acronym
URSONEONAT
Official Title
Ursodiol for Treating Parenteral Nutrition Associated Cholestasis in Neonates
Study Type
Interventional
2. Study Status
Record Verification Date
September 2013
Overall Recruitment Status
Completed
Study Start Date
October 2008 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
March 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Ibrahim Mohamed
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine whether ursodiol is effective in the treatment of parenteral nutrition associated cholestasis in neonates.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cholestasis
Keywords
parenteral nutrition associated cholestasis in neonates, parenteral nutrition induced cholestasis in preterms, Bile duct obstruction, biliary stasis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ursodiol
Arm Type
Experimental
Arm Description
Participants assigned in this arm receive an ursodiol suspension at 20mg/ml.
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
A placebo suspension that looks like the ursodiol suspension used.
Intervention Type
Drug
Intervention Name(s)
Ursodiol
Other Intervention Name(s)
Urso, ursodeoxycholic acid
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
Secondary Outcome Measure Information:
Title
Peak value of biomarkers associated with cholestasis (Gamma-glutamyl transpeptidase, Alkaline phosphatase, conjugated bilirubin)
Time Frame
at least once a week, during cholestasis
Title
1- Other hepatic marker (Aspartate transaminase, alanine transaminase, albumin blood level)
Time Frame
at least once a week, during cholestasis
Title
Length required to minimal enteral feeding (120mL/kg/day) measured in days.
Time Frame
From birth to outcome (usually less than 21 days)
Title
Weight gain (in g/kg/day)
Time Frame
From birth to resolution of cholestasis (very varuiable but usually less than 3 months)
Title
Adverse effects linked to ursodiol
Time Frame
From beginning to the end of the medication (average 4 weeks)
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ibrahim Mohamed, MB ChB, DIS P
Organizational Affiliation
St. Justine's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Josianne Malo, B.Pharm, M.Sc.
Organizational Affiliation
St. Justine's Hospital
Official's Role
Study Director
Facility Information:
Facility Name
CHU Sainte-Justine
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H3T 1C5
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
16435058
Citation
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.
Results Reference
background
PubMed Identifier
18223390
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.
Results Reference
background
PubMed Identifier
15343182
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. doi: 10.1016/j.jpeds.2004.05.038.
Results Reference
background
PubMed Identifier
15686266
Citation
Venigalla S, Gourley GR. Neonatal cholestasis. Semin Perinatol. 2004 Oct;28(5):348-55. doi: 10.1053/j.semperi.2004.09.008.
Results Reference
background
PubMed Identifier
12208100
Citation
McKiernan PJ. Neonatal cholestasis. Semin Neonatol. 2002 Apr;7(2):153-65. doi: 10.1053/siny.2002.0103.
Results Reference
background
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Ursodiol for Treating Parenteral Nutrition Associated Cholestasis in Neonates
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