Acute Respiratory Failure With HypoxiaPhase 2SuPPeRNCT01937884
Supplemental Parenteral Nutrition in Pediatric Respiratory Failure
A Phase 2 study testing Parenteral Nutrition in people with Acute Respiratory Failure With Hypoxia and Malnutrition, run by University of Arizona at 1 site in United States.
Trial summary
Optimal delivery of nutritional support during critical illness is central to appropriate intensive care unit management, and yet fundamental gaps in knowledge exist regarding timing, route, dose, and type of nutritional support for critically ill infants and children. Read more about this study
- Who is it for?
- Ages 1 month to 16 years
- Conditions the study is for
- Acute Respiratory Failure With Hypoxia, Malnutrition
- What is being tested?
- Parenteral Nutrition
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2013to Aug 2018
- Phase
- Phase 2
- 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 1 month to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Admitted to study hospital pediatric intensive care unit (PICU),
- One month to 16 years of age,
- Exhibits Acute Hypoxemic Respiratory Failure as defined as: PaO2/FiO2 ≤ 300 or SpO2/FiO2 ≤ 260, No evidence of cardiac dysfunction, Mechanically ventilated,
- Require artificial nutrition,
- Anticipate placement of central venous line within 24 hours of admission
Who cannot join
- Premature infants and neonates < 37 weeks corrected gestational age,
- Transfer patient on an established enteral or parenteral nutritional regimen,
- Known allergy to lactulose or mannitol,
- Pregnant,
- Admit BMI >30,
- Thoracic trauma, abdominal trauma, and/or active intracranial bleeding,
Show all 14Show fewer
- Anuric renal failure, previous bowel surgery and/or short gut syndrome,
- Cannot be enterally fed within 24 hours of admission according to the admitting physician,
- On extracorporeal membrane oxygenation (ECMO),
- Expected survival <24 hours or limitations to aggressive ICU care (DNR),
- Receiving active CPR when admitted to the PICU,
- A pre-existing bronchopleural fistula,
- Previously enrolled and randomized into this protocol,
- Actively enrolled in another clinical trial which at the discretion of the PI would conflict with this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Arizona Medical Center
Tucson, Arizona, 85724-5073
About this study
Optimal delivery of nutritional support during critical illness is central to appropriate intensive care unit management, and yet fundamental gaps in knowledge exist regarding timing, route, dose, and type of nutritional support for critically ill infants and children. Understanding how to optimize nutritional support during pediatric critical illness is important because even brief periods of malnutrition in infancy result in permanent negative effects on long-term neurocognitive development. Optimized nutrition support is a way to improve morbidity for survivors of pediatric critical illness. Parenteral nutrition (PN) supplementation could improve long-term neurocognitive outcome for pediatric critical illness by preventing acute malnutrition, but has unknown effects on intestinal barrier function; a proposed mechanism for late sepsis and infectious complications during critical illness.
While randomized controlled trials (RCT) support early PN in premature infants and late PN in critically ill adults, the optimal time to begin PN is unknown for critically ill infants and children. Acute malnutrition may develop within 48 hours of admission in critically ill infants and children, and repleted energy stores are predictive of survival. And yet, due to concerns for PN-associated infectious morbidity, current PICU standard of care is to supplement with PN only in children who fail to enterally feed, as late as 7 days into their admission. Delays in nutrition may have long-term effects on cognitive outcome in older infants and children. In premature infants, PN begun within hours of birth results in improved 18-month neurocognitive outcome without an increase in infectious complications. An RCT is needed to determine if early PN in critically ill infants and children prevents acute malnutrition and improves short and long-term outcomes of PICU hospitalization.
The central hypothesis of this proposal is that optimized early protein and calorie delivery will improve nutritional outcomes and intestinal barrier function for critically ill infants and children. The overall purpose of this study is to evaluate the efficacy and safety of early PN as a supplement to enteral nutrition to improve nutritional delivery, nutritional outcomes, and intestinal barrier function for infants and children with acute respiratory failure who are mechanically ventilated in the pediatric intensive care unit.
- Being tested
- Parenteral Nutrition
- Medical subject headings
- Malnutrition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Parenteral NutritionDrug
| Study group | Role | What they receive |
|---|---|---|
| Early Parenteral Nutrition | Experimental | Patients receive supplemental parenteral nutrition within 12 hours of enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. Receives: Drug: Parenteral Nutrition |
| Late Parenteral Nutrition | Active comparator | Patients receive supplemental parenteral nutrition 96 hours after enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. Receives: Drug: Parenteral Nutrition |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modified Prognostic Inflammatory and Nutritional Index (PINI)
The change day 0 to day 5 of the modified Prognostic Inflammatory and Nutritional Index (PINI) is a quantitative method to monitor the relation between markers of nutrition and acute phase proteins. It allows assessment of nutrition markers in the context of acute inflammation and in response to early enteral nutrition. A higher baseline PINI score indicates higher degree of inflammation. The modified PINI is calculated by the the ratio of (C-Reactive Protein(mg/dL) x Fibrinogen (mg/dL))/ (Transferrin (mg/dL) x Transthyretin (mg/dL)). The average change in the modified PINI from day 0 to day 5 critically ill children receiving early enteral nutrition is a decrease by 5.3 +/- 3.2 (mean +/- standard error of the mean) (Briassoulis et.al. Nutrition 2001). A larger negative number for the change from day 0 to day 5 indicates a greater degree of inflammation resolution.
Measured: Change in PINI from day 0 to day 5
Secondary outcomes (5)
Cumulative Percent of Daily Goal Calories Achieved
Evaluate percentage of cumulative goal calories achieved through parenteral and enteral routes in both study arms until patient exits study participation. Measure is calculated by (sum of kcal delivered over days of study participation/number of days in study).
Measured: baseline and daily through day 7
Plasma Intestinal Fatty Acid Binding Protein (I-FABP)
The percent change in plasma Intestinal Fatty Acid Binding Protein from baseline to study day 5, prior to late PN initiation
Measured: baseline and day 5
Plasma Citrulline
Evaluates absolute plasma citrulline concentration as a measure of functional enterocyte mass. A higher citrulline concentration indicates a higher functional enterocyte mass. Healthy children have an average citrulline concentration of 25 +/- 9 uMol/L. Assessed on day 0 and day 5, results reported for day 0 and 5. Outcome analysis on difference between treatment groups on day 5.
Measured: baseline and day 5
Plasma Claudin 3
As a measure of enterocyte tight junctions, calculate the percent change in plasma claudin 3 concentrations from baseline (day 0) and study day 5, prior to late PN administration.
Measured: baseline through hour 96
Gastrointestinal Permeability
Gastrointestinal permeability measured with the ratio of urinary recovery of lactulose and mannitol on day 5 of study participation. The range of values is generally reported as 0.02 to 2.2 with a higher value indicating greater gastrointestinal permeability. Values obtained on day 0 and day 5, day 5 reported.
Measured: day 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2013 (estimated)
- Study startAug 2013
- Primary completionAug 2018
- Study completionAug 2018
Why it stopped: Unable to enroll patients
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 Acute Respiratory Failure With HypoxiaStudies of the same condition, open and under way.
- More trials run by University of ArizonaThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Katri Typpo, University of Arizona
- Investigators
- Katri V Typpo, MD, MPH, Principal investigator, University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01937884
- Sponsor's protocol ID
- 13-0374
- Other IDs
- 5K12HD047349-09
- Acronym
- SuPPeR
- Status last verified
- Feb 2021
- First submitted
- 1 Sep 2013
- Last updated
- 3 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Supplemental Parenteral Nutrition in Pediatric Respiratory Failure
- ClinicalTrials.gov ID
- NCT01937884
- Acronym / sponsor ID
- SuPPeR / 13-0374
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unable to enroll patients
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Aug 2013 (actual)
- Primary completion
- Aug 2018 (actual)
- Study completion
- Aug 2018 (actual)
- First posted
- 10 Sep 2013 (estimated)
- Results
- Posted 3 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Optimal delivery of nutritional support during critical illness is central to appropriate intensive care unit management, and yet fundamental gaps in knowledge exist regarding timing, route, dose, and type of nutritional support for critically ill infants and children. Understanding how to optimize nutritional support during pediatric critical illness is important because even brief periods of malnutrition in infancy result in permanent negative effects on long-term neurocognitive development. Optimized nutrition support is a way to improve morbidity for survivors of pediatric critical illness. Parenteral nutrition (PN) supplementation could improve long-term neurocognitive outcome for pediatric critical illness by preventing acute malnutrition, but has unknown effects on intestinal barrier function; a proposed mechanism for late sepsis and infectious complications during critical illness.
While randomized controlled trials (RCT) support early PN in premature infants and late PN in critically ill adults, the optimal time to begin PN is unknown for critically ill infants and children. Acute malnutrition may develop within 48 hours of admission in critically ill infants and children, and repleted energy stores are predictive of survival. And yet, due to concerns for PN-associated infectious morbidity, current PICU standard of care is to supplement with PN only in children who fail to enterally feed, as late as 7 days into their admission. Delays in nutrition may have long-term effects on cognitive outcome in older infants and children. In premature infants, PN begun within hours of birth results in improved 18-month neurocognitive outcome without an increase in infectious complications. An RCT is needed to determine if early PN in critically ill infants and children prevents acute malnutrition and improves short and long-term outcomes of PICU hospitalization.
The central hypothesis of this proposal is that optimized early protein and calorie delivery will improve nutritional outcomes and intestinal barrier function for critically ill infants and children. The overall purpose of this study is to evaluate the efficacy and safety of early PN as a supplement to enteral nutrition to improve nutritional delivery, nutritional outcomes, and intestinal barrier function for infants and children with acute respiratory failure who are mechanically ventilated in the pediatric intensive care unit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early Parenteral Nutrition | Experimental | Drug: Parenteral NutritionPatients receive supplemental parenteral nutrition within 12 hours of enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. |
| Late Parenteral Nutrition | Active comparator | Drug: Parenteral NutritionPatients receive supplemental parenteral nutrition 96 hours after enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. |
Who may qualify
- Ages
- 1 month to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Admitted to study hospital pediatric intensive care unit (PICU),
- One month to 16 years of age,
- Exhibits Acute Hypoxemic Respiratory Failure as defined as: PaO2/FiO2 ≤ 300 or SpO2/FiO2 ≤ 260, No evidence of cardiac dysfunction, Mechanically ventilated,
- Require artificial nutrition,
- Anticipate placement of central venous line within 24 hours of admission
Key exclusion criteria (14 listed)
- Premature infants and neonates < 37 weeks corrected gestational age,
- Transfer patient on an established enteral or parenteral nutritional regimen,
- Known allergy to lactulose or mannitol,
- Pregnant,
- Admit BMI >30,
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 |
|---|---|---|
| Parenteral Nutrition | Drug | Early Parenteral Nutrition, Late Parenteral Nutrition |
Primary outcome
Modified Prognostic Inflammatory and Nutritional Index (PINI)
Time frame: Change in PINI from day 0 to day 5
The change day 0 to day 5 of the modified Prognostic Inflammatory and Nutritional Index (PINI) is a quantitative method to monitor the relation between markers of nutrition and acute phase proteins. It allows assessment of nutrition markers in the context of acute inflammation and in response to early enteral nutrition. A higher baseline PINI score indicates higher degree of inflammation. The modified PINI is calculated by the the ratio of (C-Reactive Protein(mg/dL) x Fibrinogen (mg/dL))/ (Transferrin (mg/dL) x Transthyretin (mg/dL)). The average change in the modified PINI from day 0 to day 5 critically ill children receiving early enteral nutrition is a decrease by 5.3 +/- 3.2 (mean +/- standard error of the mean) (Briassoulis et.al. Nutrition 2001). A larger negative number for the change from day 0 to day 5 indicates a greater degree of inflammation resolution.
5 secondary outcomes
Cumulative Percent of Daily Goal Calories Achieved
Time frame: baseline and daily through day 7
Plasma Intestinal Fatty Acid Binding Protein (I-FABP)
Time frame: baseline and day 5
Plasma Citrulline
Time frame: baseline and day 5
Plasma Claudin 3
Time frame: baseline through hour 96
Gastrointestinal Permeability
Time frame: day 5
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2021.
- 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.
Katri V Typpo, MD, MPH principal investigator
University of Arizona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Parenteral Nutrition in people with Acute Respiratory Failure With Hypoxia and Malnutrition, run by University of Arizona at 1 site 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 5 inclusion and 14 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: stopped early, as of the sponsor's last update on 3 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 3 Mar 2021). 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?
Modified Prognostic Inflammatory and Nutritional Index (PINI) (time frame: Change in PINI from day 0 to day 5). 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 3 Mar 2021.