Trial Outcomes & Findings for Supplemental Parenteral Nutrition in Pediatric Respiratory Failure (NCT NCT01937884)

NCT ID: NCT01937884

Last Updated: 2021-03-03

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 18 participants
• Primary outcome timeframe: Change in PINI from day 0 to day 5
• Results posted on: 2021-03-03

Participant Flow

Participant milestones

Measure	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.	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.
Overall Study STARTED	7	11
Overall Study COMPLETED	6	11
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Measure	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.	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.
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Supplemental Parenteral Nutrition in Pediatric Respiratory Failure

Baseline characteristics by cohort

Measure	Early Parenteral Nutrition n=7 Participants 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.	Late Parenteral Nutrition n=11 Participants 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.	Total n=18 Participants Total of all reporting groups
Age, Continuous	1.4 years n=5 Participants	1.1 years n=7 Participants	1.3 years n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
BMI z score	-.73 Z score n=5 Participants	-.9 Z score n=7 Participants	-0.9 Z score n=5 Participants
PELOD-2 score	8 units on a scale n=5 Participants	7 units on a scale n=7 Participants	7.5 units on a scale n=5 Participants

PRIMARY outcome

Timeframe: Change in PINI from day 0 to day 5

Population: 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.

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.

Outcome measures

Measure	Early Parenteral Nutrition n=4 Participants Patients receive supplemental parenteral nutrition within 12 hours of enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. Parenteral Nutrition	Late Parenteral Nutrition n=7 Participants Patients receive supplemental parenteral nutrition 96 hours after enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. Parenteral Nutrition
Modified Prognostic Inflammatory and Nutritional Index (PINI)	-1.6 score on a scale Standard Error 1.0	-3.2 score on a scale Standard Error 1.8

SECONDARY outcome

Timeframe: baseline and daily through day 7

Population: All patients enrolled had daily nutrition data collected until end of study participation.

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).

Outcome measures

Measure	Early Parenteral Nutrition n=7 Participants Patients receive supplemental parenteral nutrition within 12 hours of enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. Parenteral Nutrition	Late Parenteral Nutrition n=11 Participants Patients receive supplemental parenteral nutrition 96 hours after enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. Parenteral Nutrition
Cumulative Percent of Daily Goal Calories Achieved	103.8 percent of goal kcal/day Interval 98.5 to 110.2	103.4 percent of goal kcal/day Interval 86.4 to 110.0

SECONDARY outcome

Timeframe: baseline and day 5

Population: All patients enrolled in the study with IFABP results obtained at baseline and hour 96, analyzed in initial assigned groups.

The percent change in plasma Intestinal Fatty Acid Binding Protein from baseline to study day 5, prior to late PN initiation

Outcome measures

Measure	Early Parenteral Nutrition n=5 Participants Patients receive supplemental parenteral nutrition within 12 hours of enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. Parenteral Nutrition	Late Parenteral Nutrition n=8 Participants Patients receive supplemental parenteral nutrition 96 hours after enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. Parenteral Nutrition
Plasma Intestinal Fatty Acid Binding Protein (I-FABP)	2.11 percent change Interval -35.9 to 28.3	-25 percent change Interval -47.9 to 8.6

SECONDARY outcome

Timeframe: baseline and day 5

Population: Citrulline concentrations obtained for patients with plasma samples available for analysis on study day 0 and 5

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.

Outcome measures

Measure	Early Parenteral Nutrition n=7 Participants Patients receive supplemental parenteral nutrition within 12 hours of enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. Parenteral Nutrition	Late Parenteral Nutrition n=11 Participants Patients receive supplemental parenteral nutrition 96 hours after enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. Parenteral Nutrition
Plasma Citrulline day 0	10 umoL per Liter Interval 8.6 to 14.8	8 umoL per Liter Interval 4.7 to 11.0
Plasma Citrulline day 5	19.4 umoL per Liter Interval 19.0 to 32.5	14.5 umoL per Liter Interval 11.1 to 20.4

SECONDARY outcome

Timeframe: baseline through hour 96

Population: Included all patients with claudin 3 plasma concentrations reported at hour zero and 96, analyzed in groups as initially assigned.

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.

Outcome measures

Measure	Early Parenteral Nutrition n=5 Participants Patients receive supplemental parenteral nutrition within 12 hours of enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. Parenteral Nutrition	Late Parenteral Nutrition n=8 Participants Patients receive supplemental parenteral nutrition 96 hours after enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. Parenteral Nutrition
Plasma Claudin 3	29.8 percent change Interval 11.7 to 53.6	111.7 percent change Interval -8.8 to 224.1

SECONDARY outcome

Timeframe: day 5

Population: 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.

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.

Outcome measures

Measure	Early Parenteral Nutrition n=5 Participants Patients receive supplemental parenteral nutrition within 12 hours of enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. Parenteral Nutrition	Late Parenteral Nutrition n=8 Participants Patients receive supplemental parenteral nutrition 96 hours after enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. Parenteral Nutrition
Gastrointestinal Permeability	0.15 ratio Interval 0.13 to 0.78	0.17 ratio Interval 0.13 to 0.24

OTHER_PRE_SPECIFIED outcome

Timeframe: until hospital discharge or day 28 if still hospitalized

Population: All study participants

Record any hospital-defined hospital acquired infections through day 28 in all study participants.

Outcome measures

Measure	Early Parenteral Nutrition n=7 Participants Patients receive supplemental parenteral nutrition within 12 hours of enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. Parenteral Nutrition	Late Parenteral Nutrition n=11 Participants Patients receive supplemental parenteral nutrition 96 hours after enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. Parenteral Nutrition
Number of Participants With Hospital-Acquired Infections	0 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days

Population: Determined for all study participants.

Death of a study patient do to any cause measured up to 28 days after study enrollment.

Outcome measures

Measure	Early Parenteral Nutrition n=7 Participants Patients receive supplemental parenteral nutrition within 12 hours of enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. Parenteral Nutrition	Late Parenteral Nutrition n=11 Participants Patients receive supplemental parenteral nutrition 96 hours after enrollment. Titrated with enteral nutrition to achieve target goal calories and protein. Parenteral Nutrition
28-day Mortality	2 Participants	0 Participants

Adverse Events

Early Parenteral Nutrition

Serious events: 0 serious events

Other events: 5 other events

Deaths: 2 deaths

Late Parenteral Nutrition

Serious events: 5 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Early Parenteral Nutrition n=7 participants at risk 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.	Late Parenteral Nutrition n=11 participants at risk 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.
Blood and lymphatic system disorders Deep vein thrombosis	0.00% 0/7 • 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.	27.3% 3/11 • Number of events 3 • 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.
Infections and infestations Hospital-Acquired infection	0.00% 0/7 • 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.	9.1% 1/11 • Number of events 1 • 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.
Gastrointestinal disorders Aspiration of gastric contents	0.00% 0/7 • 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.	9.1% 1/11 • Number of events 1 • 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.

Other adverse events

Measure	Early Parenteral Nutrition n=7 participants at risk 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.	Late Parenteral Nutrition n=11 participants at risk 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.
Respiratory, thoracic and mediastinal disorders Desaturation < 85%	71.4% 5/7 • Number of events 10 • 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.	45.5% 5/11 • Number of events 9 • 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.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/7 • 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.	9.1% 1/11 • Number of events 1 • 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.

Additional Information

Dr. Katri Typpo

University of Arizona

Phone: 5206265485

Email: ktyppo@email.arizona.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place