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| ID | Type | Description | Link |
|---|---|---|---|
| 5K12HD047349-09 | U.S. NIH Grant/Contract | View source |
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Unable to enroll patients
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| Name | Class |
|---|---|
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Parenteral Nutrition | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | baseline and daily through day 7 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Hospital-Acquired Infections | Record any hospital-defined hospital acquired infections through day 28 in all study participants. | until hospital discharge or day 28 if still hospitalized |
| 28-day Mortality |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Katri V Typpo, MD, MPH | University of Arizona | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Arizona Medical Center | Tucson | Arizona | 85724-5073 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Early Parenteral Nutrition | Patients receive supplemental parenteral nutrition within 12 hours of enrollment. Titrated with enteral nutrition to achieve target goal calories and protein over the one week study period. |
| FG001 | Late Parenteral Nutrition | Patients receive supplemental parenteral nutrition 96 hours after enrollment if meeting < 80% of caloric goals with enteral nutrition alone. Titrated with enteral nutrition to achieve target goal calories and protein over the one week study period. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Early Parenteral Nutrition | Patients receive supplemental parenteral nutrition within 12 hours of enrollment. Titrated with enteral nutrition to achieve target goal calories and protein over the one week study period. |
| BG001 | Late Parenteral Nutrition |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Patients with central venous access and/or arterial access removed at study day 5 did not have blood drawn for PINI measurement. All patients with paired PINI values from day 0 and day 5 obtained are analyzed based on initial group assignment. | Posted | Mean | Standard Error | score on a scale | Change in PINI from day 0 to day 5 |
Adverse event data were collected over 14 days, from time of patient enrollment
Adverse event reporting follows the clinicaltrials.gov definitions and includes all-cause mortality, serious adverse events, and other adverse events.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Early Parenteral Nutrition | Patients receive supplemental parenteral nutrition within 12 hours of enrollment. Titrated with enteral nutrition to achieve target goal calories and protein over the one week study period. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Deep vein thrombosis | Blood and lymphatic system disorders | Systematic Assessment | Identification of a deep vein thrombosis by ultrasound imaging |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Desaturation < 85% | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Desaturation event with SaO2 < 85% |
This study was discontinued early due to slow enrollment. The small study size limits interpretation of clinical and biochemical outcomes data.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Katri Typpo | University of Arizona | 5206265485 | ktyppo@email.arizona.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 6, 2017 | Jan 25, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D044342 | Malnutrition |
| ID | Term |
|---|---|
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D010288 | Parenteral Nutrition |
| ID | Term |
|---|---|
| D005248 | Feeding Methods |
| D013812 | Therapeutics |
| D018529 | Nutritional Support |
| D044623 | Nutrition Therapy |
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| 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 | 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. | 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. | 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. | day 5 |
Death of a study patient do to any cause measured up to 28 days after study enrollment.
| 28 days |
Patients receive supplemental parenteral nutrition 96 hours after enrollment if meeting < 80% of caloric goals with enteral nutrition alone. Titrated with enteral nutrition to achieve target goal calories and protein over the one week study period. |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| BMI z score | The BMI Z-Score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean. BMI Z-score cut-points of < - 2.0, > 1.0, > 2.0, > 3.0 define wasted, at risk of overweight, overweight and obese, respectively. BMI z scores were calculated used CDC growth charts for children 2 years of age and older. For children under 2 years of age the weight for age Z score is reported. | Median | Inter-Quartile Range | Z score |
|
| PELOD-2 score | The Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score allows assessment of the severity of organ dysfunction on a continuous scale. The score incorporates assessment of 5 organ system dysfunction (Cardiovascular, Neurologic, Respiratory, Hematologic, and Renal). Component scores for each organ system can be calculated, only the composite score which reflects baseline severity of illness and organ dysfunction is reported in our study. The minimum PELOD-2 score is 0 and the maximum is 33. A higher PELOD-2 score indicates a higher probability of death. | Median | Inter-Quartile Range | units on a scale |
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| ID | Title | Description |
|---|---|---|
| OG000 | Early Parenteral Nutrition | Patients receive supplemental parenteral nutrition within 12 hours of enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. Parenteral Nutrition |
| OG001 | Late Parenteral Nutrition | Patients receive supplemental parenteral nutrition 96 hours after enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. Parenteral Nutrition |
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| Secondary | 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). | All patients enrolled had daily nutrition data collected until end of study participation. | Posted | Median | Inter-Quartile Range | percent of goal kcal/day | baseline and daily through day 7 |
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| Secondary | 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 | All patients enrolled in the study with IFABP results obtained at baseline and hour 96, analyzed in initial assigned groups. | Posted | Median | Inter-Quartile Range | percent change | baseline and day 5 |
|
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|
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| Secondary | 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. | Citrulline concentrations obtained for patients with plasma samples available for analysis on study day 0 and 5 | Posted | Median | Inter-Quartile Range | umoL per Liter | baseline and day 5 |
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| Secondary | 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. | Included all patients with claudin 3 plasma concentrations reported at hour zero and 96, analyzed in groups as initially assigned. | Posted | Median | Inter-Quartile Range | percent change | baseline through hour 96 |
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| Secondary | 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. | Analysis of lactulose and mannitol urinary concentrations performed on all patients who received the lactulose and mannitol study test and with urinary samples obtained on day 5. | Posted | Median | Inter-Quartile Range | ratio | day 5 |
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| Other Pre-specified | Number of Participants With Hospital-Acquired Infections | Record any hospital-defined hospital acquired infections through day 28 in all study participants. | All study participants | Posted | Count of Participants | Participants | until hospital discharge or day 28 if still hospitalized |
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| Other Pre-specified | 28-day Mortality | Death of a study patient do to any cause measured up to 28 days after study enrollment. | Determined for all study participants. | Posted | Count of Participants | Participants | 28 days |
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| 2 |
| 7 |
| 0 |
| 7 |
| 5 |
| 7 |
| EG001 | Late Parenteral Nutrition | Patients receive supplemental parenteral nutrition 96 hours after enrollment if meeting < 80% of caloric goals with enteral nutrition alone. Titrated with enteral nutrition to achieve target goal calories and protein over the one week study period. | 0 | 11 | 5 | 11 | 6 | 11 |
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| Hospital-Acquired infection | Infections and infestations | Systematic Assessment | Hospital-determined hospital acquired infections |
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| Aspiration of gastric contents | Gastrointestinal disorders | Systematic Assessment | Aspiration event as determined by the Clinical team |
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| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment | Glucose value >200 mg/dL |
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| day 5 |
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