Complete Shielding of Multivitamins to Reduce Toxic Peroxides in the Parenteral Nutrition: A Pilot Study

Not Applicable

Completed

• Conditions: Infant, Premature, Diseases; Infant, Newborn, Disease; Bronchopulmonary Dysplasia; Parenteral Nutrition; Lung Diseases; Respiratory Tract Disease; Pathologic Processes
• Interventions: Other: Standard Care; Other: Photo-protection

• Registration Number: NCT04234152
• Lead Sponsor: St. Justine's Hospital

Brief Summary

The purpose of this study is to examine if a new and simple method involving complete photo-protection of multivitamins only (since sampling through infusion) will result in a significant reduction of peroxide contamination of parenteral nutrition compared to standard method of parenteral nutrition preparation and infusion in extremely preterm infants.

Detailed Description

Hypothesis and Objectives:

The investigators propose, in this pilot study, a new and simple method involving complete photo-protection of multivitamins (MV) only (since sampling through infusion) and they hypothesize that this method will be readily applicable and will result in a significant reduction of peroxide contamination of parenteral nutrition (PN) compared to standard care of PN preparation and infusion method.

In Vitro Results Using This Proposed Photo-Protection Method:

This method has reduced the quantity of infused peroxides (as equivalent H2O2). When adding the generated peroxides over 5 hours (5 samples: at times 0, 30 minutes, 1, 3 and 5 hours), the total peroxides were 1270± 47 micromolar (μM) without photo-protection vs. 710±16 μM with this method, leading to 45% reduction of peroxides (data presented as a poster presentation in the Pediatric academic societies meeting , 2018, Poster number 2874.625). This reduction is comparable to the previously reported in vitro data for the whole PN complete photo-protection that reported 50% reduction of peroxides.

Specific objective of this pilot study:

To examine if this new and simple method will be feasible in clinical practice and will result in a significant reduction of urinary peroxide concentration when compared to standard PN compounding and infusion technique.

Innovation:

The investigators' team's long experience in this field permitted the identification of the interaction between light and MV (specifically riboflavin) that leads to doubling the amount of peroxides contaminating the PN. The complexity of complete photo-protection encountered by the team to conduct small uni-center studies and the incapacity to introduce the complete photo-protection in daily clinical practice led the team to create this simple intervention that will address the problem at its origin in a practical way. All trials, including complete PN photo-protection, faced the complexity of keeping MV away from light while needing to prepare the PN admixture under the light of a sterile hood. Added to this was the complexity of completely covering the PN bag while compounding the admixture. Light exposure may also occur during the transportation of the PN from the hospital pharmacy to the neonatal unit (even with special attention to the bottom of the bag and the area around the tubing being well covered).

The proposed intervention will eliminate all these complex procedures by directly sampling the MV in a photo-protected syringe, transporting it in this syringe, and directly infusing the MV into the photo-protected intravenous lines through its infusion into the patient.

Study Timeline

• Study First Submitted: 2020-01-08
• Study First Submitted QC: 2020-01-15
• Study First Posted: 2020-01-21
• Study Start: 2020-11-23
• Primary Completion: 2021-10-27
• Study Completion: 2022-01-17
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-27
• Last Update Posted: 2022-10-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

• Infants < 28 weeks of gestational age
• Obtaining parental consent before the start of the first PN prescribed by the attending physician

Exclusion Criteria

• Significant congenital malformations
• Infant is currently enrolled in another trial -unless approval of trial research team-
• Parent inability to comprehend and consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of care	Standard Care	Includes infants in whom the standard method of preparation and infusion of PN will be applied. This arm will be stratified to male and female 1:1
MV Photo-protection	Photo-protection	Includes infants in whom the new procedure of MV separation and photo-protection will be applied. This arm will be stratified to male and female 1:1

Primary Outcome Measures

Name	Time	Method
Change in urine peroxides concentration	Baseline, 48 hours post-parenteral nutrition and on day 7 of life	From each urine sample, an aliquot (0.2 ml) will be used for creatinin measurement whereas another (0.5 ml) will be used for peroxide determination using the ferrous oxidation/xylenol orange technique. H2O2 will serve for the standard curve. The results will be expressed as μmol equ H2O2/mg creatinine.

Secondary Outcome Measures

Name	Time	Method
Urinary ascorbylperoxide (AscOOH)	On day 7 of life	Urine AscOOH concentration will be determined using Mass spectrometry.
Serum inflammatory cytokines: Interleukin 1 alpha (IL-1alpha) and beta (IL-1beta), Interleukin 6 (IL-6), Interleukin 8 (IL-8), Interleukin (IL-10), Tumor Necrosis Factor alpha (TNF-alpha), Vascular Endothelial Growth Factor (VEGF)	On day 7 of life	Multiplex assay (Luminex R\&D systems), using 0.1 ml of blood
Serum inflammatory cytokines: IL-1alpha, IL-1beta, IL-6, IL-8, IL-10, TNF-alpha, VEGF	At 36 weeks Post-Menstrual Age	Multiplex assay (Luminex R\&D systems), using 0.1 ml of blood
Clinical outcome - Incidence of significant Patent Ductus Arteriosus (PDA)	From birth to discharge home, an average of 4 months	PDA requiring medical or surgical treatment according to the treating neonatologist will be reported and compared.
Clinical outcome - infant anthropometry: weight	At 36 weeks Post-Menstrual Age	Weight in grams
Whole blood glutathione redox potential	At 36 weeks Post-Menstrual Age	Whole blood levels of glutathione (GSH) and glutathione disulfide (GSSG) will be measured by capillary electrophoresis as previously described by our team, using 0.5 ml of blood. The whole blood redox potential (mV) will be calculated, using the Nernst equation.
Clinical outcome - length of mechanical ventilation (invasive, non-invasive)	From birth to discharge home, an average of 4 months	Total number of days on mechanical ventilation (both invasive and non invasive respiratory support)
Clinical outcome - length of supplemental oxygen (in days)	From birth to discharge home, an average of 4 months	Total number of days on Nasal cannula O2 supplements
Clinical outcome - Incidence and stage of necrotizing enterocolitis (According to Bell's classification)	From birth to discharge home, an average of 4 months	Necrotizing enterocolitis stages as defind by Bell stage II or higher. The incidence in the two arms will be reported and compared
Clinical outcome - Incidence of Bronchopulmonary dysplasia (BPD) and BPD severity (Mild, moderate, sever)	At 36 weeks Post-Menstrual Age	According to the National Institute of Child Health and Human Development (NICHD) criteria (Jobe Alan H.,2001)
Clinical outcome - Mortality rate	At 36 weeks Post-Menstrual Age	Death before 36 weeks post menstrual age
Clinical outcome - Incidence and grade of intraventricular hemorrhage (IVH), according to Papille criteria	From birth to discharge home, an average of 4 months	Any intraventricular hemorrhage (IVH), IVH grade III and IV in each arm will be reported and compared.
Clinical outcome - Incidence of significant liver cholestasis (defined as two or more consecutive conjugated bilirubin values ≥ 34 μmol/L)	From birth to discharge home, an average of 4 months	Cholestasis is defined as two or more consecutive conjugated bilirubin values ≥ 34 μmol/L. The incidence of cholestasis in each arm will be reported and compared.
Clinical outcome - infant anthropometry: length	At 36 weeks Post-Menstrual Age	Length in centimeters
Clinical outcome - Incidence and stage of Retinopathy Of Prematurity (ROP) (highest stage)	From birth to discharge home, an average of 4 months	The incidence of ROP stage II and higher as defined by the National Eye Institute will be reported and compared.
Clinical outcome - infant anthropometry: head circumference	At 36 weeks Post-Menstrual Age	Head circumference in centimeters
Clinical outcome - length of hospital stay (in days)	From birth to discharge home, an average of 4 months	Total number of days till discharge home

Trial Locations

Locations (2)

University of Montreal, Sainte-Justine Hospital; 🇨🇦 Montréal, Canada

CHU Sainte-Justine; 🇨🇦 Montréal, Quebec, Canada