CholestasisPhase 3NCT02357576
Standard Lipid Therapy vs IVFE Minimization for Prevention of PNALD
A Phase 3 study testing Intralipid 20% I.V. Fat Emulsion in people with Cholestasis, run by University of Michigan at 5 sites in United States.
Trial summary
Parenteral nutrition-associated cholestasis (PNAC) and liver disease (PNALD) are associated with significant morbidity and mortality in neonates and is felt to be exacerbated by soybean-based lipid emulsions. Much research is currently being directed at identifying ways to reduce this risk. Read more about this study
- Who is it for?
- Ages Up to 1 year
- Conditions the study is for
- Cholestasis
- What is being tested?
- Intralipid 20% I.V. Fat Emulsion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 5 sitesUnited States
- Study dates
- 21 May 2016to 8 Nov 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 1 year
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- neonates and infants who are at least 28 weeks corrected gestational age at the time of enrollment who are parenteral nutrition (PN) naive
- current direct bilirubin <2 mg/dL
- any of the following conditions:
- meconium ileus and peritonitis
- gastroschisis
- omphalocele >4cm or with liver herniated outside of the abdominal cavity
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- necrotizing enterocolitis requiring surgical intervention
- volvulus
- intestinal atresia with >50% bowel loss
Who cannot join
- weight <1 kg
- metabolic pathway defect which is associated with liver dysfunction in the neonatal period, including: hereditary fructose intolerance, galactosemia due to transferase deficiency and neonatal tyrosinemia, and/or disorder of lipid metabolism
- hepatic insufficiency as documented by either a biopsy with cirrhosis and/or marked aberration in synthetic function
- renal failure
- primary or secondary liver disease, regardless of liver function (includes hepatitis)
- use of extracorporeal membrane oxygenation (ECMO)
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- suspected congenital obstruction of the hepatobiliary tree
- documented active infection which may be communicable, including infections hepatitis or HIV
- previous receipt of choleretic agents
- currently receiving phenobarbital or other barbiturates
- history of PNAC
- direct bilirubin >=2 mg/dL at time of enrollment
- congenital or acquired anomaly which will require major cardiovascular surgery
- major congenital or chromosomal anomaly
- hypoxic ischemic encephalopathy
- congenital defect of the brain
- major seizure disorder
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of Michigan
Ann Arbor, Michigan, 48109
University of Colorado/Children's Hospital Colorado
Aurora, Colorado, 80045
University of Florida
Gainesville, Florida, 32601
Primary Children's Hospital
Salt Lake City, Utah, 84132
Seattle Children's Hospital
Seattle, Washington, 98105
About this study
Official title: Phase 3 Study of Standard Lipid Therapy Versus Intravenous Fat Emulsion Minimization for the Prevention of Parenteral Nutrition-Associated Liver Disease
Parenteral nutrition-associated cholestasis (PNAC) and liver disease (PNALD) are associated with significant morbidity and mortality in neonates and is felt to be exacerbated by soybean-based lipid emulsions. Much research is currently being directed at identifying ways to reduce this risk. Reduction of the dose of soybean-based lipid given as a component of parenteral nutrition is one possible strategy. In this study we will compare standard dosing of soybean-based lipid (up to 3/kg/day) with a minimized dose (1 g/kg/day) and evaluate for the development of cholestasis and adequate growth between the two groups. Longterm followup will include an assessment of neurodevelopmental outcomes at 12 and 24 months of age.
Funding source - FDA OOPD
- Conditions
- Cholestasis
- Being tested
- Intralipid 20% I.V. Fat Emulsion
- Medical subject headings
- Cholestasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intralipid 20% I.V. Fat EmulsionDrug
| Study group | Role | What they receive |
|---|---|---|
| Reduced Lipid | Experimental | Subjects will receive a minimized dose (1 g/kg/day) of the soybean-based lipid component of parenteral nutrition. Receives: Drug: Intralipid 20% I.V. Fat Emulsion |
| Standard Lipid | Active comparator | Subjects will receive the standard dose (up to 3 g/kg/day) of the soybean-based lipid component of parenteral nutrition. Receives: Drug: Intralipid 20% I.V. Fat Emulsion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Rise of Direct Bilirubin as a Function of Time
The rate of rise (change over time) of direct bilirubin was compared between the two groups at different time points.
Measured: 12 weeks
Secondary outcomes (19)
Prevalence of Parenteral Nutrition-associated Cholestasis (PNAC) (Direct Bilirubin ≥2 mg/dL)
The number of participants who had a direct bilirubin ≥2 mg/dL were compared between the standard and reduced lipid groups. Bilirubin data was collected from baseline until 7 days after PN has been discontinued, but not to exceed a total of 12 weeks.
Measured: 12 weeks
Prevalence of Severe Parenteral Nutrition-associated Cholestasis (PNAC) (Direct Bilirubin ≥4 mg/dL in Subjects on Parenteral Nutrition for at Least 2 Weeks)
The number of participants with severe PNAC defined as a direct bilirubin ≥4 mg/dL were compared between the standard and reduced lipid groups. Bilirubin data was collected from baseline until 7 days after PN has been discontinued, but not to exceed a total of 12 weeks.
Measured: 12 weeks
The Time to Development of PNAC
The time to development was compared between the standard and reduced lipid groups.
Measured: 12 weeks
The Time to Development of Severe PNAC
The time to development from randomization was compared between the standard and reduced lipid groups.
Measured: 12 weeks
Peak Total Bilirubin Level
The peak (highest) total bilirubin collected from each subject from after week 1 to end of treatment. This was compared between the standard and reduced lipid groups.
Measured: 12 weeks
Peak Direct Bilirubin Level
The peak (highest) direct bilirubin collected from each subject from after week 1 to end of treatment. This was compared between the standard and reduced lipid groups.
Measured: 12 weeks
The Prevalence of Essential Fatty Acid Deficiency (EFAD)
The number of participants who experienced EFAD was compared between the standard and reduced lipid groups.
Measured: 12 weeks
Adequacy of Growth as Evaluated by Z-scores for Weight
Z-scores were compared between subjects in the two treatment groups by week. Z-scores are the number of standard deviations above (positive value) or below (negative value) the median on the FENTON and WHO growth charts. Fenton scores were used for infants born <37 weeks gestation. WHO scores were used for infants born at ≥37 weeks gestation.
Measured: 12 weeks
Adequacy of Growth as Evaluated by Z-scores for Height
Z-scores were compared between subjects in the two treatment groups. Z-scores are the number of standard deviations above (positive value) or below (negative value) the median on the FENTON and WHO growth charts. Fenton scores were used for infants born <37 weeks gestation. WHO scores were used for infants born at ≥37 weeks gestation.
Measured: 12 weeks
Adequacy of Growth as Evaluated by Z-scores for Head Circumference
Z-scores were compared between subjects in the two treatment groups. Z-scores are the number of standard deviations above (positive value) or below (negative value) the median on the FENTON and WHO growth charts. Fenton scores were used for infants born <37 weeks gestation. WHO scores were used for infants born at ≥37 weeks gestation.
Measured: 12 weeks
Adverse Events, as Defined by Any Episode of Sepsis and Catheter-related Blood Stream Infections
The number of episodes were compared between the standard and reduced lipid groups of suspected sepsis episodes, NEC, or catheter-related blood stream infections.
Measured: 12 weeks
Bayley Scales for Infant and Toddler Development (BSID-III) at One Year
The Bayley Scales of Infant and Toddler Development (BSID-III) is designed to assess developmental functioning of infants and toddlers, ages 1 month to 42 months. The instrument includes five distinct scales, of which three scales and associated subscales are utilized for the purposes of this study: cognitive, language (receptive and expressive communication) and motor (fine motor and gross motor). Raw scores are converted to scaled scores using age-standardized norm. The cognitive scaled scores range from 1-19. 1 is a low score and 19 is a high score. The Language scaled scores are calculated by adding the Receptive Communication scores ranging from 1-19 and the Expressive communication scores ranging from 1-19 to give the Language Scaled score of 2-38. The Motor scaled scores are calculated by adding the Fine Motor scores ranging from 1-19 and the Gross Motor scores ranging from 1-19 to give the Motor scaled ranging from 2-38. Higher scores are better than lower scores.
Measured: 1 year
Bayley Scales for Infant and Toddler Development (BSID-III) at Two Years
The Bayley Scales of Infant and Toddler Development (BSID-III) is designed to assess developmental functioning of infants and toddlers, ages 1 month to 42 months. The instrument includes five distinct scales, of which three scales and associated subscales are utilized for the purposes of this study: cognitive, language (receptive and expressive communication) and motor (fine motor and gross motor). Raw scores are converted to scaled scores using age-standardized norm. The cognitive scaled scores range from 1-19. 1 is a low score and 19 is a high score. The Language scaled scores are calculated by adding the Receptive Communication scores ranging from 1-19 and the Expressive communication scores ranging from 1-19 to give the Language Scaled score of 2-38. The Motor scaled scores are calculated by adding the Fine Motor scores ranging from 1-19 and the Gross Motor scores ranging from 1-19 to give the Motor scaled ranging from 2-38. Higher scores are better than lower scores.
Measured: 2 years
MacArthur-Bates Communicative Development Inventories (CDI)
The MacArthur-Bates Communicative Development Inventories (CDI) are parent report instruments which capture information about children's developing abilities in early language. Scores are reported as percentiles compared to age-standardized norms. Higher scores are better than lower scores.
Measured: 2 years
Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 1 of 2
Dichotomous scores are generated based on cut-off scores, which identify subjects to be at risk. The problem scale measures behaviors of the child that if present, represent a problem. The competence scale measures behaviors of the child that if absent, represent a problem. BITSEA percentile rankings are determined from a table that has a limited range and are adjusted for age and sex. A high problem score leads to a low problem percentile. A high competence score leads to a high competence percentile. Percentile rankings for both problem and competence scores range from "4% or less" to "26% or higher". 4 is the lowest percentile score and 26 is the highest percentile score. The 25th percentile is the lower limit of the average range. Higher percentile scores are better than lower percentile scores in both problem and competence categories.
Measured: 2 years
Gross Motor Function Classification System (GMFCS)
This classification is based on observation with a scale of 1-5. A lower number classification is better than a higher classification, with 1 being the best.
Measured: 2 years
Behavioral Assessment System for Children-Third Edition (BASC3) Part 1 of 2
The Behavioral Assessment System for Children-Third Edition is a comprehensive set of forms that helps to understand the behaviors and emotions of children. Scores are reported as T-Scores. T-Scores range from 0-120. In a normative population, the mean of standard scores is 50, and standard deviation is 10. For Externalizing Problems T-Score, Internalizing Problems T-Score, Behavioral Symptoms Index T-Score, Clinical Probability Index T-Score, and Functional Impairment Index T-Score lower scores are better than higher scores. For these categories, higher scores are more problematic with scores between 60-70 regarded as "at risk" and scores 70 and above regarded as clinically significant and requiring further assessment and possible treatment. For Adaptive Skills T-Score, a higher score is better than a lower score. For Adaptive Skills T-Score, lower scores are more problematic with scores between 30-40 regarded as "at risk" and scores at or below 30 regarded as clinically significant.
Measured: 2 years
Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2
The Behavioral Assessment System for Children-Third Edition is a comprehensive set of forms that helps to understand the behaviors and emotions of children. For Overall Executive Functioning Index, Attentional Control Index, Behavioral Control Index, and Emotional Control Index, scores are "Not Elevated" or "Elevated". Not Elevated is better than Elevated.
Measured: 2 years
Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 2 of 2
Dichotomous scores are generated based on cut-off scores, which identify subjects to be at risk. The problem scale measures behaviors of the child that if present, represent a problem. The competence scale measures behaviors of the child that if absent, represent a problem.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2015 (estimated)
- Study start21 May 2016
- Primary completion12 Oct 2017
- Study completion8 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CholestasisStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- Seattle Children's Hospital, University of Florida, Primary Children's Hospital, University of Colorado, Denver
- Responsible party
- Principal investigator, Meghan A. Arnold, MD, University of Michigan
- Investigators
- Meghan A Arnold, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02357576
- Sponsor's protocol ID
- HUM00075458
- Other IDs
- 1R01FD005085-01A1
- Status last verified
- Dec 2020
- First submitted
- 2 Feb 2015
- Last updated
- 17 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3 Study of Standard Lipid Therapy Versus Intravenous Fat Emulsion Minimization for the Prevention of Parenteral Nutrition-Associated Liver Disease
- ClinicalTrials.gov ID
- NCT02357576
- Acronym / sponsor ID
- HUM00075458
- Conditions
- Cholestasis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- Seattle Children's Hospital, University of Florida, Primary Children's Hospital, University of Colorado, Denver
- Study start
- 21 May 2016 (actual)
- Primary completion
- 12 Oct 2017 (actual)
- Study completion
- 8 Nov 2019 (actual)
- First posted
- 6 Feb 2015 (estimated)
- Results
- Posted 23 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Parenteral nutrition-associated cholestasis (PNAC) and liver disease (PNALD) are associated with significant morbidity and mortality in neonates and is felt to be exacerbated by soybean-based lipid emulsions. Much research is currently being directed at identifying ways to reduce this risk. Reduction of the dose of soybean-based lipid given as a component of parenteral nutrition is one possible strategy. In this study we will compare standard dosing of soybean-based lipid (up to 3/kg/day) with a minimized dose (1 g/kg/day) and evaluate for the development of cholestasis and adequate growth between the two groups. Longterm followup will include an assessment of neurodevelopmental outcomes at 12 and 24 months of age.
Funding source - FDA OOPD
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Reduced Lipid | Experimental | Drug: Intralipid 20% I.V. Fat EmulsionSubjects will receive a minimized dose (1 g/kg/day) of the soybean-based lipid component of parenteral nutrition. |
| Standard Lipid | Active comparator | Drug: Intralipid 20% I.V. Fat EmulsionSubjects will receive the standard dose (up to 3 g/kg/day) of the soybean-based lipid component of parenteral nutrition. |
Who may qualify
- Ages
- Up to 1 year
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- neonates and infants who are at least 28 weeks corrected gestational age at the time of enrollment who are parenteral nutrition (PN) naive
- current direct bilirubin <2 mg/dL
- any of the following conditions:
- meconium ileus and peritonitis
- gastroschisis
Key exclusion criteria (17 listed)
- weight <1 kg
- metabolic pathway defect which is associated with liver dysfunction in the neonatal period, including: hereditary fructose intolerance, galactosemia due to transferase deficiency and neonatal tyrosinemia, and/or disorder of lipid metabolism
- hepatic insufficiency as documented by either a biopsy with cirrhosis and/or marked aberration in synthetic function
- renal failure
- primary or secondary liver disease, regardless of liver function (includes hepatitis)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intralipid 20% I.V. Fat Emulsion | Drug | Reduced Lipid, Standard Lipid |
Primary outcome
Rate of Rise of Direct Bilirubin as a Function of Time
Time frame: 12 weeks
The rate of rise (change over time) of direct bilirubin was compared between the two groups at different time points.
19 secondary outcomes
Prevalence of Parenteral Nutrition-associated Cholestasis (PNAC) (Direct Bilirubin ≥2 mg/dL)
Time frame: 12 weeks
Prevalence of Severe Parenteral Nutrition-associated Cholestasis (PNAC) (Direct Bilirubin ≥4 mg/dL in Subjects on Parenteral Nutrition for at Least 2 Weeks)
Time frame: 12 weeks
The Time to Development of PNAC
Time frame: 12 weeks
The Time to Development of Severe PNAC
Time frame: 12 weeks
Peak Total Bilirubin Level
Time frame: 12 weeks
Peak Direct Bilirubin Level
Time frame: 12 weeks
The Prevalence of Essential Fatty Acid Deficiency (EFAD)
Time frame: 12 weeks
Adequacy of Growth as Evaluated by Z-scores for Weight
Time frame: 12 weeks
Adequacy of Growth as Evaluated by Z-scores for Height
Time frame: 12 weeks
Adequacy of Growth as Evaluated by Z-scores for Head Circumference
Time frame: 12 weeks
Adverse Events, as Defined by Any Episode of Sepsis and Catheter-related Blood Stream Infections
Time frame: 12 weeks
Bayley Scales for Infant and Toddler Development (BSID-III) at One Year
Time frame: 1 year
Bayley Scales for Infant and Toddler Development (BSID-III) at Two Years
Time frame: 2 years
MacArthur-Bates Communicative Development Inventories (CDI)
Time frame: 2 years
Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 1 of 2
Time frame: 2 years
Gross Motor Function Classification System (GMFCS)
Time frame: 2 years
Behavioral Assessment System for Children-Third Edition (BASC3) Part 1 of 2
Time frame: 2 years
Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2
Time frame: 2 years
Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 2 of 2
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Meghan A Arnold, MD principal investigator
University of Michigan
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Intralipid 20% I.V. Fat Emulsion in people with Cholestasis, run by University of Michigan at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Rise of Direct Bilirubin as a Function of Time (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2020.