Supplemental Parenteral Nutrition in Pediatric Respiratory Failure

NCT01937884 | Terminated Phase 2 Results

• 2 other identifiers: 13-03745K12HD047349-09
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Acute Respiratory Failure With Hypoxia; Malnutrition

Outcome Measures

Primary Outcomes (1)

• 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.

  Change in PINI from day 0 to day 5

Secondary Outcomes (5)

• Cumulative Percent of Daily Goal Calories Achieved

  baseline and daily through day 7

• Plasma Intestinal Fatty Acid Binding Protein (I-FABP)

  baseline and day 5

• Plasma Citrulline

  baseline and day 5

• Plasma Claudin 3

  baseline through hour 96

• Gastrointestinal Permeability

  day 5

Other Outcomes (2)

• Number of Participants With Hospital-Acquired Infections

  until hospital discharge or day 28 if still hospitalized

• 28-day Mortality

  28 days

Study Arms (2)

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.

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.

Drug: Parenteral Nutrition

Interventions

Parenteral Nutrition DRUG

Early Parenteral Nutrition; Late Parenteral Nutrition

Eligibility Criteria

• Age: 1 Month - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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,
• 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.

Sponsors & Collaborators

• University of Arizona: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of Arizona Medical Center

Tucson, Arizona, 85724-5073, United States

Location

MeSH Terms

Conditions

Malnutrition

Interventions

Parenteral Nutrition

Condition Hierarchy (Ancestors)

Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Feeding Methods; Therapeutics; Nutritional Support; Nutrition Therapy

Limitations and Caveats

This study was discontinued early due to slow enrollment. The small study size limits interpretation of clinical and biochemical outcomes data.

Results Point of Contact

• Title: Dr. Katri Typpo
• Organization: University of Arizona

ktyppo@email.arizona.edu

5206265485

Study Officials

• Katri V Typpo, MD, MPH

  University of Arizona

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 1, 2013
• First Posted: September 10, 2013
• Study Start: August 1, 2013
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: March 3, 2021
• Results First Posted: March 3, 2021

Record last verified: 2021-02

Locations

US (1)