Clinical trial NCT04234152: Complete Shielding of Multivitamins to Reduce Toxic Peroxides in the Parenteral Nutrition: A Pilot Study
Official title: Complete Shielding of Multivitamins to Reduce Toxic Peroxides in the Parenteral Nutrition: A Pilot Study (C SMART-PN, Pilot)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parenteral Nutrition
Infant, Premature, Diseases
Infant, Newborn, Disease
Lung Diseases
Respiratory Tract Disease
Bronchopulmonary Dysplasia
Pathologic Processes
Keywords: Photo-protection of Multivitamins
Oxidative Stress
Ascorbyl peroxide
Urine peroxides
Lead sponsor: St. Justine's Hospital
Sponsor class: OTHER
First posted: 2020-01-21
Enrollment: 35
Sex: ALL
Minimum age (years): 1
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in urine peroxides concentration
timeFrame: Baseline, 48 hours post-parenteral nutrition and on day 7 of life
Secondary outcomes:
measure: Urinary ascorbylperoxide (AscOOH)
timeFrame: On day 7 of life
measure: Whole blood glutathione redox potential
timeFrame: On day 7 of life
measure: Whole blood glutathione redox potential
timeFrame: At 36 weeks Post-Menstrual Age
measure: 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)
timeFrame: On day 7 of life
measure: Serum inflammatory cytokines: IL-1alpha, IL-1beta, IL-6, IL-8, IL-10, TNF-alpha, VEGF
timeFrame: At 36 weeks Post-Menstrual Age
measure: Clinical outcome - Incidence of Bronchopulmonary dysplasia (BPD) and BPD severity (Mild, moderate, sever)
timeFrame: At 36 weeks Post-Menstrual Age
measure: Clinical outcome - Mortality rate
timeFrame: At 36 weeks Post-Menstrual Age
measure: Clinical outcome - length of mechanical ventilation (invasive, non-invasive)
timeFrame: From birth to discharge home, an average of 4 months
measure: Clinical outcome - length of supplemental oxygen (in days)
timeFrame: From birth to discharge home, an average of 4 months
measure: Clinical outcome - Incidence and stage of necrotizing enterocolitis (According to Bell's classification)
timeFrame: From birth to discharge home, an average of 4 months
measure: Clinical outcome - Incidence and grade of intraventricular hemorrhage (IVH), according to Papille criteria
timeFrame: From birth to discharge home, an average of 4 months
measure: Clinical outcome - Incidence of significant liver cholestasis (defined as two or more consecutive conjugated bilirubin values ≥ 34 μmol/L)
timeFrame: From birth to discharge home, an average of 4 months
measure: Clinical outcome - Incidence and stage of Retinopathy Of Prematurity (ROP) (highest stage)
timeFrame: From birth to discharge home, an average of 4 months
measure: Clinical outcome - Incidence of significant Patent Ductus Arteriosus (PDA)
timeFrame: From birth to discharge home, an average of 4 months
measure: Clinical outcome - infant anthropometry: weight
timeFrame: At 36 weeks Post-Menstrual Age
measure: Clinical outcome - infant anthropometry: length
timeFrame: At 36 weeks Post-Menstrual Age
measure: Clinical outcome - infant anthropometry: head circumference
timeFrame: At 36 weeks Post-Menstrual Age
measure: Clinical outcome - length of hospital stay (in days)
timeFrame: From birth to discharge home, an average of 4 months
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
city: Montréal
country: Canada
facility: University of Montreal, Sainte-Justine Hospital
Study officials:
affiliation: Sainte-Justine Research center, Sainte-Justine hospital, University of Montreal
name: Ibrahim Mohamed, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Thibeault DW. The precarious antioxidant defenses of the preterm infant. Am J Perinatol. 2000;17(4):167-81. doi: 10.1055/s-2000-9422.
citation: Mohamed I, Elremaly W, Rouleau T, Lavoie JC. Oxygen and parenteral nutrition two main oxidants for extremely preterm infants: 'It all adds up'. J Neonatal Perinatal Med. 2015;8(3):189-97. doi: 10.3233/NPM-15814091.
citation: Saugstad OD. Oxygen and oxidative stress in bronchopulmonary dysplasia. J Perinat Med. 2010 Nov;38(6):571-7. doi: 10.1515/jpm.2010.108. Epub 2010 Aug 31.
citation: Laborie S, Lavoie JC, Pineault M, Chessex P. Contribution of multivitamins, air, and light in the generation of peroxides in adult and neonatal parenteral nutrition solutions. Ann Pharmacother. 2000 Apr;34(4):440-5. doi: 10.1345/aph.19182.
citation: Laborie S, Lavoie JC, Chessex P. Increased urinary peroxides in newborn infants receiving parenteral nutrition exposed to light. J Pediatr. 2000 May;136(5):628-32. doi: 10.1067/mpd.2000.105131.
citation: Bassiouny MR, Almarsafawy H, Abdel-Hady H, Nasef N, Hammad TA, Aly H. A randomized controlled trial on parenteral nutrition, oxidative stress, and chronic lung diseases in preterm infants. J Pediatr Gastroenterol Nutr. 2009 Mar;48(3):363-9. doi: 10.1097/mpg.0b013e31818c8623.
citation: Mohamed I, Elremaly W, Rouleau T, Lavoie JC. Ascorbylperoxide Contaminating Parenteral Nutrition Is Associated With Bronchopulmonary Dysplasia or Death in Extremely Preterm Infants. JPEN J Parenter Enteral Nutr. 2017 Aug;41(6):1023-1029. doi: 10.1177/0148607116643704. Epub 2016 Apr 1.
citation: Elremaly W, Mohamed I, Mialet-Marty T, Rouleau T, Lavoie JC. Ascorbylperoxide from parenteral nutrition induces an increase of redox potential of glutathione and loss of alveoli in newborn guinea pig lungs. Redox Biol. 2014 May 20;2:725-31. doi: 10.1016/j.redox.2014.05.002. eCollection 2014.
citation: Lavoie JC, Rouleau T, Chessex P. Interaction between ascorbate and light-exposed riboflavin induces lung remodeling. J Pharmacol Exp Ther. 2004 Nov;311(2):634-9. doi: 10.1124/jpet.104.070755. Epub 2004 Jul 13.
citation: Chessex P, Harrison A, Khashu M, Lavoie JC. In preterm neonates, is the risk of developing bronchopulmonary dysplasia influenced by the failure to protect total parenteral nutrition from exposure to ambient light? J Pediatr. 2007 Aug;151(2):213-4. doi: 10.1016/j.jpeds.2007.04.029.
citation: Chessex P, Laborie S, Nasef N, Masse B, Lavoie JC. Shielding Parenteral Nutrition From Light Improves Survival Rate in Premature Infants. JPEN J Parenter Enteral Nutr. 2017 Mar;41(3):378-383. doi: 10.1177/0148607115606407. Epub 2016 Sep 30.