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

Lung Diseases Clinical Trial

— C-SMART-PN  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04234152
• Other study ID #: 2020-2713
• Status: Completed
• Phase: N/A
• Start date: November 23, 2020
• Est. completion date: January 17, 2022

Study information

• Verified date: October 2022
• Source: St. Justine's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: January 17, 2022
• Est. primary completion date: October 27, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Minute to 2 Days

Eligibility

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

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia
• Infant, Newborn, Disease
• Infant, Newborn, Diseases
• Infant, Premature, Diseases
• Lung Diseases
• Parenteral Nutrition
• Pathologic Processes
• Respiratory Tract Disease
• Respiratory Tract Diseases

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	CHU Sainte-Justine	Montréal	Quebec
Canada	University of Montreal, Sainte-Justine Hospital	Montréal

Sponsors (1)

Lead Sponsor	Collaborator
St. Justine's Hospital

Country where clinical trial is conducted

Canada, 

References & Publications (11)

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. — View 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. — View 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. Review. — View 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. — View 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. — View 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. — View 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. Epub 2004 Jul 13. — View 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. — View 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. — View 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. Review. — View Citation

Thibeault DW. The precarious antioxidant defenses of the preterm infant. Am J Perinatol. 2000;17(4):167-81. Review. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in urine peroxides concentration	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.	Baseline, 48 hours post-parenteral nutrition and on day 7 of life
Secondary	Urinary ascorbylperoxide (AscOOH)	Urine AscOOH concentration will be determined using Mass spectrometry.	On day 7 of life
Secondary	Whole blood glutathione redox potential	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.	On day 7 of life
Secondary	Whole blood glutathione redox potential	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.	At 36 weeks Post-Menstrual Age
Secondary	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)	Multiplex assay (Luminex R&D systems), using 0.1 ml of blood	On day 7 of life
Secondary	Serum inflammatory cytokines: IL-1alpha, IL-1beta, IL-6, IL-8, IL-10, TNF-alpha, VEGF	Multiplex assay (Luminex R&D systems), using 0.1 ml of blood	At 36 weeks Post-Menstrual Age
Secondary	Clinical outcome - Incidence of Bronchopulmonary dysplasia (BPD) and BPD severity (Mild, moderate, sever)	According to the National Institute of Child Health and Human Development (NICHD) criteria (Jobe Alan H.,2001)	At 36 weeks Post-Menstrual Age
Secondary	Clinical outcome - Mortality rate	Death before 36 weeks post menstrual age	At 36 weeks Post-Menstrual Age
Secondary	Clinical outcome - length of mechanical ventilation (invasive, non-invasive)	Total number of days on mechanical ventilation (both invasive and non invasive respiratory support)	From birth to discharge home, an average of 4 months
Secondary	Clinical outcome - length of supplemental oxygen (in days)	Total number of days on Nasal cannula O2 supplements	From birth to discharge home, an average of 4 months
Secondary	Clinical outcome - Incidence and stage of necrotizing enterocolitis (According to Bell's classification)	Necrotizing enterocolitis stages as defind by Bell stage II or higher. The incidence in the two arms will be reported and compared	From birth to discharge home, an average of 4 months
Secondary	Clinical outcome - Incidence and grade of intraventricular hemorrhage (IVH), according to Papille criteria	Any intraventricular hemorrhage (IVH), IVH grade III and IV in each arm will be reported and compared.	From birth to discharge home, an average of 4 months
Secondary	Clinical outcome - Incidence of significant liver cholestasis (defined as two or more consecutive conjugated bilirubin values = 34 µmol/L)	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.	From birth to discharge home, an average of 4 months
Secondary	Clinical outcome - Incidence and stage of Retinopathy Of Prematurity (ROP) (highest stage)	The incidence of ROP stage II and higher as defined by the National Eye Institute will be reported and compared.	From birth to discharge home, an average of 4 months
Secondary	Clinical outcome - Incidence of significant Patent Ductus Arteriosus (PDA)	PDA requiring medical or surgical treatment according to the treating neonatologist will be reported and compared.	From birth to discharge home, an average of 4 months
Secondary	Clinical outcome - infant anthropometry: weight	Weight in grams	At 36 weeks Post-Menstrual Age
Secondary	Clinical outcome - infant anthropometry: length	Length in centimeters	At 36 weeks Post-Menstrual Age
Secondary	Clinical outcome - infant anthropometry: head circumference	Head circumference in centimeters	At 36 weeks Post-Menstrual Age
Secondary	Clinical outcome - length of hospital stay (in days)	Total number of days till discharge home	From birth to discharge home, an average of 4 months