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

Sponsor

St. Justine's Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04234152

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Parenteral Nutrition Infant, Premature, Diseases Infant, Newborn, Disease Lung Diseases Respiratory Tract Disease Bronchopulmonary Dysplasia Pathologic Processes	Other: Photo-protection Other: Standard Care	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

32 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Masking Description:

The primary outcome is the concentration of peroxides in the urine. The urine samples will not indicate the arm of the study.

Primary Purpose:

Prevention

Official Title:

Complete Shielding of Multivitamins to Reduce Toxic Peroxides in the Parenteral Nutrition: A Pilot Study (C SMART-PN, Pilot)

Actual Study Start Date :

Nov 23, 2020

Anticipated Primary Completion Date :

Dec 23, 2021

Anticipated Study Completion Date :

Dec 23, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MV 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	Other: Photo-protection The MV solution is delivered from producing companies in amber vials. The MV will be sampled by the pharmacy technician in a syringe that is photo-protected with a white label indicating the subject study name, protocol number and the infusion rate. The MV will be transported to the unit in the same photo-protected syringe. In the neonatal unit, this syringe will be installed in the pump and connected to photo-protected extension duration.
Placebo Comparator: Standard of 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	Other: Standard Care This group will receive the standard practice of PN compounding in the pharmacy followed by infusion in standard infusion kit available in Sainte-Justine's Hospital.

Arm

Intervention/Treatment

Experimental: MV 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

Other: Photo-protection

The MV solution is delivered from producing companies in amber vials. The MV will be sampled by the pharmacy technician in a syringe that is photo-protected with a white label indicating the subject study name, protocol number and the infusion rate. The MV will be transported to the unit in the same photo-protected syringe. In the neonatal unit, this syringe will be installed in the pump and connected to photo-protected extension duration.

Placebo Comparator: Standard of 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

Other: Standard Care

This group will receive the standard practice of PN compounding in the pharmacy followed by infusion in standard infusion kit available in Sainte-Justine's Hospital.

Outcome Measures

Primary Outcome Measures

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

Urinary ascorbylperoxide (AscOOH) [On day 7 of life]
Urine AscOOH concentration will be determined using Mass spectrometry.
Whole blood glutathione redox potential [On day 7 of life]
Whole blood levels of glutathione (GSH) and glutathione disulfide (GSSG) will be measured by capillary electrophoresis as previously described by the investigators' team, using 0.5 ml of blood. The whole blood redox potential (mV) will be calculated, using the Nernst equation.
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.
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 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 - 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 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 - 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 - 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
Clinical outcome - infant anthropometry: length [At 36 weeks Post-Menstrual Age]
Length in centimeters
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Minute to 2 Days

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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