Ursodiol for Treating Parenteral Nutrition Associated Cholestasis in Neonates

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

Detailed Description
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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.

Official Title
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Ursodiol for Treating Parenteral Nutrition Associated Cholestasis in Neonates

Conditions
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Cholestasis

Intervention / Treatment
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* Drug: Ursodiol
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ursodiol<br>Participants assigned in this arm receive an ursodiol suspension at 20mg/ml. | Drug: Ursodiol<br>* 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.<br>* Other names: ursodeoxycholic acid;|
| Placebo Comparator: placebo<br>A placebo suspension that looks like the ursodiol suspension used. | Drug: placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of parenteral nutrition associated cholestasis (in days) |  | at the end of cholestasis (when conjugated bilirubin < 34 mmol/L) average of 4 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak value of biomarkers associated with cholestasis (Gamma-glutamyl transpeptidase, Alkaline phosphatase, conjugated bilirubin) |  | at least once a week, during cholestasis | 
| 1- Other hepatic marker (Aspartate transaminase, alanine transaminase, albumin blood level) |  | at least once a week, during cholestasis | 
| Length required to minimal enteral feeding (120mL/kg/day) measured in days. |  | From birth to outcome (usually less than 21 days) | 
| Weight gain (in g/kg/day) |  | From birth to resolution of cholestasis (very varuiable but usually less than 3 months) | 
| Adverse effects linked to ursodiol |  | From beginning to the end of the medication (average 4 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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parenteral nutrition associated cholestasis in neonates, parenteral nutrition induced cholestasis in preterms, Bile duct obstruction, biliary stasis