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Clinical Trial Details — Status: Enrolling by invitation

Administrative data

NCT number NCT04031508
Other study ID # R-2019-785-044
Secondary ID
Status Enrolling by invitation
Phase Phase 2
First received
Last updated
Start date August 12, 2019
Est. completion date December 2024

Study information

Verified date February 2024
Source Coordinación de Investigación en Salud, Mexico
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the effect of a parenteral emulsion containing n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in fish oil on clinical outcomes, markers of inflammation and oxidative stress, and pain in neonates with persistent pulmonary hypertension of the newborn (PPHN) compared with those who receive an emulsion containing soy oil and medium-chain triglycerides (MCT) without n-3 LC-PUFA.


Description:

Background. Persistent pulmonary hypertension of the newborn (PPHN), is a syndrome characterized by difficulty to provide normal pulmonary vasodilatation at birth or after birth, which may be related to right ventricular dysfunction, congenital diaphragmatic hernia, sepsis, and meconium aspiration. This condition is understudied. PPHN causes pulmonary vascular resistance (PVR) that decreases left pulmonary artery flow (LPA), meaning that blood cannot be oxygenated in the lungs, leading to low oxygen delivery to all organs. Expensive medication along with ventilator support may help, but the latter and PPHN increase the production of the inflammatory mediators such as pro-inflammatory cytokines and markers of oxidative stress, which cause cell toxicity. To treat the hernia, infants undergo corrective surgery, which further increases the production of inflammatory markers and worsens oxidative stress. As a result, the pain of the surgery also worsens the hypoxemia and respiratory insufficiency in the newborn. PPHN is associated with chronic lung disease (CLD). To date, there is no effective treatment for neonates with PPHN, and around one-third of patients may not respond to current management, leading to the death of up to 33% of infants in developed countries. In Mexico, the mortality rate from PPHN may reach 80%, which is an unacceptable outcome at a high cost. Therefore, the prevention or reduction of the severity of PPHN is actively sought. Previous reports have shown that the n-3 long-chain polyunsaturated fatty acids (LC-PUFA), such as docosahexaenoic acid (DHA) improves the nutritional status and clinical outcomes in septic newborn reduce systemic inflammation and organ dysfunction in newborns who underwent cardiovascular surgery with a shorter stay in the neonatal intensive care unit. In addition, those babies received lower amounts of analgesics. Other authors have shown that n-3 LC-PUFA reduces oxidative stress. In experimental models of PPHN, the EPA and DHA from Omegaven (fish oil) increased pulmonary artery flow and decrease pulmonary vascular resistance. In the current project, it is hypothesized that n-3 LC-PUFA improves clinical outcomes such as decreasing pulmonary vascular pressure and markers of inflammation and oxidative stress in neonates with PPHN. This hypothesis has not been evaluated. Objective. The purpose of this study is to evaluate the effect of a parenteral emulsion containing n-3 LC-PUFA in fish oil on clinical outcomes, markers of inflammation and oxidative stress, and pain in neonates with PPHN compared with those who receive an emulsion containing soy and medium-chain triglycerides (MCT) without n-3 LC-PUFA. Methodology. A double-blind clinical trial will be carried out on Mexican newborns diagnosed with PPHN. The control group will receive intravenous nutrition support including a lipid emulsion based on soy oil plus MCT (control group) and the intervention group will receive a lipid emulsion based on soy oil, MCT, olive oil, and fish oil (n-3 LC-PUFA group); both groups will receive a dose of lipid (3 g/kg/d maximum), through total parenteral nutrition (TPN) for at least 7 days. The effect of n-3 LC-PUFA will be evaluated on: 1. Clinical outcomes, nutritional status, the manifestation of pain 2. Markers of inflammation 3. Oxidative stress markers To compare the groups, the Exact Fisher´s, Student's t, or U-Mann-Whitney tests will be applied as appropriate. To adjust the effect of n-3 LC-PUFA for confounders such as fatty acid background and medication, Repeated Measures ANOVA and binary logistic regression will be performed.


Recruitment information / eligibility

Status Enrolling by invitation
Enrollment 40
Est. completion date December 2024
Est. primary completion date July 2024
Accepts healthy volunteers No
Gender All
Age group 1 Hour to 15 Days
Eligibility Inclusion Criteria: - Plan to administrate TPN for at least 7 days - Clinical, gasometric, and echocardiographic diagnosis of congenital diaphragmatic hernia. - Gestational age >=34 weeks. - Written informed consent signed by both parents after an explanation of the objectives, procedures and possible risks and benefits of the research, along with the signature of two witnesses Exclusion Criteria: - Diagnosis of complex congenital cardiopathy - Cyanotic congenital cardiology defect - Insufficiency of the tricuspid valve - Immunosuppressive disease. HIV has been associated with PPHN and human herpesvirus with vascular remodeling, perivascular macrophages, and lung fibrosis - Clinical entities that preclude the total parenteral nutrition for one day or longer. - Presence of profuse and persistent haemorrhage at any level Elimination criteria - Parents who withdraw their consent. - Starting a drug at doses for nonclotting treatment such as heparin, enoxaparin. - Development of profuse and persistent haemorrhage at any level after receiving vitamin K treatment.

Study Design


Related Conditions & MeSH terms


Intervention

Combination Product:
lipid injectable emulsion with Fish oil
TPN will start at 1.5-2.0 g/kg/d of the lipid emulsion, increasing 1.0 g/kg/d until a maximum of 3.0 g/kg/d for at least 7 days.

Locations

Country Name City State
Mexico Unit of Medical Research in Nutrition Mexico Ciudad De Mexico

Sponsors (3)

Lead Sponsor Collaborator
Coordinación de Investigación en Salud, Mexico Universidad Nacional Autonoma de Mexico, University of Southampton

Country where clinical trial is conducted

Mexico, 

Outcome

Type Measure Description Time frame Safety issue
Primary Change on systolic pressure of pulmonary artery Measured by echocardiography in millimeters of mercury (mm/Hg) Before surgery (baseline), 24 hour, 48 hour, 72 hour, day 7, day 14 and day 21 post-surgery.
Primary Preductal partial pressure of carbon (PaCO2) Good response if the carbon in blood is <60-70 mmHg measured by gasometry in arterial blood Before surgery (baseline), 24 hour, 48 hour, 72 hour and day 7 post-surgery.
Primary Change in Preductal and postductal oxygen saturation (SatO2) It is a measure of oxygenation in hemoglobin. It is preductal if the measurement id on hand, and postductal if it is on foot, determined by an pulse oximeter in percentage Before surgery (baseline), 24 hour, 48 hour, 72 hour, day 7, day 14 and day 21 post-surgery.
Primary Inspired fraction of oxygen (FiO2) Oxygen concentration supplied by ventilation support in percentage Before surgery (baseline), 24 hour, 48 hour, 72 hour, day 7, day 14 and day 21 post-surgery.
Primary Growth velocity and Nutritional status Measurement of body weight in grams, length, and head circumference in centimeters (if clinical condition allows it) to obtain grams/kg/d, cm/week, Z score, and eutrophic or undernutrition outcome using the Fenton's standard reference of growth and/or World Health Organization as appropriate for preterm or term infants, respectively. Before surgery (baseline), day 7, day 14 and day 21 post-surgery.
Primary Pain manifestation Pain will be measured with the COMFORT scale computed by eight sections with scores from 1 to 5 each. Before surgery (baseline), 24 hour, 48 hour, 72 hour, day 7, day 14 and day 21 post-surgery.
Secondary Concentration of plasma cytokines as inflammatory markers Determination of pro and anti-inflammatory cytokines interleukin (IL)-1beta, tumoral necrosis factor-alpha, IL-6, IL-8, IL-10, IL-12 (p70) (pg/milliliter) in plasma by luminex-based immunoassay. Before surgery (baseline), 24 hour, 48 hour, 72 hour, and day 7 post-surgery.
Secondary Concentration of inflammatory derived-lipid mediators Determination lipid mediators such as eicosanoids and resolvin(s) in ng/ml by liquid chromatography coupled to mass spectrometry. Before surgery (baseline), 24 hour, 48 hour, 72 hour, and day 7 post-surgery.
Secondary Concentration of total free thiols This will be measured in urine by ELISA in pg/milliliter At study entry, before surgery (2 baselines), and once a day until day 7 after surgery, then at 14 and 21 days-post-surgery.
Secondary Concentration of nitrotyrosine This will be measured in urine by ELISA in micromol per liter (uM) At study entry, before surgery (2 baselines), and once a day until day 7 after surgery, then at 14 and 21 days-post-surgery.
Secondary Concentration of the nuclear factor erythroid 2-related factor 2 (Nrf2) This will be measured in urine by ELISA in pg/milliliter At study entry, before surgery (2 baselines), and once a day until day 7 after surgery, then at 14 and 21 days-post-surgery.
Secondary Concentration of Ratio of F2-isoprostanes (F2-isop) and F2-isofurans (F2-isof) This ratio will be measured in urine in nmol/liter by Liquid chromatography coupled to mass spectrometry. At study entry, before surgery (2 baselines), and once a day until day 7 after surgery, then at 14 and 21 days-post-surgery.
Secondary Chronic Lung Disease It will be evaluated with the need of supplementary Oxygen and/or medication to improve lung function At hospital discharge or 56 day-old, at 6 months and one year of age
See also
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Completed NCT05050045 - Echocardiographic Screening of Healthy Neonates for Measuring Pulmonary Artery Pressure