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Trial record 32 of 68 for:    tpn

Effect of a Parenteral Emulsion With Omega3 on PPHN (PPHN-N3)

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ClinicalTrials.gov Identifier: NCT04031508
Recruitment Status : Not yet recruiting
First Posted : July 24, 2019
Last Update Posted : July 24, 2019
Sponsor:
Information provided by (Responsible Party):
Coordinación de Investigación en Salud, Mexico

Brief 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.

Condition or disease Intervention/treatment Phase
Pulmonary Hypertension of Newborn Diaphragm Defect Dietary Supplement: Parenteral emulsion Phase 2

Detailed 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 with 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. When patients have PPHN secondary to a diaphragmatic hernia, they 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 bronchopulmonary dysplasia (BPD), a chronic lung disease. 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 death up to 33% of the infants in developed countries. In Mexico, the mortality rate from PPHN reaches 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 the pulmonary vascular resistance. In the current project, it is hypothesized that n-3 LC-PUFA improves clinical outcomes such as decreasing pulmonary vascular resistance and markers of inflammation and oxidative stress but increases LPA flow in neonates with PPHN. This hypothesis has not been evaluated in PPHN.

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 in Mexican newborns diagnosed with PPHN. 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 between 3-4 g/kg/d, through total parenteral nutrition (TPN) for at least 14 days and a maximum of 21 days.

The effect of n-3 LC-PUFA will be evaluated on:

  1. Clinical outcomes, nutritional status, perception od 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Use of a parenteral emulsion that is used as routine nutrition for newborns but not evaluated for persistent pulmonary hypertension.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The attendant gastroenterologist has the randomized allocation and will indicate the type of emulsion during the recruitment. Each emulsion will be designed as a code A or B.
Primary Purpose: Prevention
Official Title: Effect of a Parenteral Emulsion Parenteral With Long-chain Polyunsaturated Fatty Acids Omega 3 on Clinical Outcomes, Inflammatory and Oxidative Stress Markers in Neonates With Persistent Pulmonary Hypertension
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : July 2022


Arm Intervention/treatment
Experimental: Omega 3
The experimental group will receive a parenteral emulsion containing soy oil, MCT, olive oil and n-3 LCPUFA in fish oil
Dietary Supplement: Parenteral emulsion
TPN will start at 2.0 g/kg/d of the lipid emulsion, increasing 1.0 g/kg/d until a maximum of 4.0 g/kg/d for at least 14 days.

Sham Comparator: Control group
The Control group will receive a parenteral emulsion containing soy oil and MCT
Dietary Supplement: Parenteral emulsion
TPN will start at 2.0 g/kg/d of the lipid emulsion, increasing 1.0 g/kg/d until a maximum of 4.0 g/kg/d for at least 14 days.




Primary Outcome Measures :
  1. Change on Systolic pressure of pulmonary artery [ Time Frame: Before surgery (baseline), 24 hour, 48 hour, 72 hour, day 7, day 14 and day 21 post-surgery. ]
    measured by echocardiography in mm/Hg

  2. Change on Mean pressure of the pulmonary artery [ Time Frame: Before surgery (baseline), 24 hour, 48 hour, 72 hour, day 7, day 14 and day 21 post-surgery. ]
    measured by echocardiography in mm/Hg

  3. Change on Pulmonary output [ Time Frame: Before surgery (baseline), 24 hour, 48 hour, 72 hour, day 7, day 14 and day 21 post-surgery. ]
    measured by echocardiography in units

  4. Change on Cardiac output [ Time Frame: Before surgery (baseline), 24 hour, 48 hour, 72 hour, day 7, day 14 and day 21 post-surgery. ]
    measured by echocardiography in mL/min

  5. Change on Preductal partial pressure of oxygen (PaO2) [ Time Frame: Before surgery (baseline), 24 hour, 48 hour, 72 hour, day 7, day 14 and day 21 post-surgery. ]
    Measure the amount of oxygen in blood measured by gasometry in arterial blood in mmHg

  6. Change on Preductal and postductal oxygen saturation (SatO2) [ Time Frame: Before surgery (baseline), 24 hour, 48 hour, 72 hour, day 7, day 14 and day 21 post-surgery. ]
    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

  7. Change on Inspired fraction of oxygen (FiO2) [ Time Frame: Before surgery (baseline), 24 hour, 48 hour, 72 hour, day 7, day 14 and day 21 post-surgery. ]
    Oxygen concentration supplied by ventilation support in percentage

  8. Change on Nutritional status [ Time Frame: Before surgery (baseline), day 7, day 14 and day 21 post-surgery. ]
    Measurement of body weight in grams, length and head circumference in centimeters to obtain an eutrophic or undernutrition outcome using the Fenton's standard reference of growth and/or WHO as appropriate for preterm or term infants, respectively.

  9. Change of pain perception [ Time Frame: Before surgery (baseline), 24 hour, 48 hour, 72 hour, day 7, day 14 and day 21 post-surgery. ]
    Pain will be measured with COMFORT scale computed by the sum of 8 sections with scores from 1 to 5. The sum will be scored as mild (<10 points), moderate (10-20 points) and severe (>20 points)


Secondary Outcome Measures :
  1. Concentration of plasma cytokines as inflammatory markers [ Time Frame: Before surgery (baseline), 24 hour, 48 hour, 72 hour, day 7, day, and day 14 post-surgery. ]
    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.

  2. Concentration of inflammatory derived-lipid mediators [ Time Frame: Before surgery (baseline), 24 hour, 48 hour, 72 hour, day 7, day, and day 14 post-surgery. ]
    Determination lipid mediators such as eicosanoids and resolvin(s) in ng/ml by liquid chromatography coupled to mass spectrometry.

  3. Concentration of total free thiols [ Time Frame: At study entry, before surgery (2 baselines), and once a day until day 7 after surgery, then at 14 and 21 days-post-surgery. ]
    This will be measured in urine by ELISA in pg/milliliter

  4. Concentration of the ratio of nitrites/nitrates [ Time Frame: At study entry, before surgery (2 baselines), and once a day until day 7 after surgery, then at 14 and 21 days-post-surgery. ]
    This will be measured in urine by ELISA in uM/milliliter

  5. Concentration of reduced/oxidized glutathione ratio (GSH/GSSG) [ Time Frame: At study entry, before surgery (2 baselines), and once a day until day 7 after surgery, then at 14 and 21 days-post-surgery. ]
    This will be measured in urine by ELISA in uM/milliliter

  6. Concentration of 8-hydroxy-2-deoxyguanosine (8OHgD) [ Time Frame: At study entry, before surgery (2 baselines), and once a day until day 7 after surgery, then at 14 and 21 days-post-surgery. ]
    This will be measured in urine by ELISA in pg/milliliter

  7. Concentration of Ratio of F2-isoprostanes (F2-isop) and F2-isofuranes (F2-isof) [ Time Frame: At study entry, before surgery (2 baselines), and once a day until day 7 after surgery, then at 14 and 21 days-post-surgery. ]
    This ratio will be measured in urine in nmol/liter by Liquid chromatography coupled to mass spectrometry.



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Ages Eligible for Study:   up to 15 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The requirement of TPN for at least 14 days
  • Clinical, gasometric, and echocardiographic diagnosis of pulmonary arterial hypertension associated with diaphragm defect.
  • 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 with PPHN
  • 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 hemorrhage 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 hemorrhage at any level after receiving vitamin K treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04031508


Contacts
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Contact: Mariela Bernabe-Garcia, PhD +52 55 56276944 marielabernabe1@gmail.com
Contact: Maricela Rodriguez-Cruz, PhD +52 55 56276944 maricela.rodriguez.cruz@gmail.com

Sponsors and Collaborators
Coordinación de Investigación en Salud, Mexico
Investigators
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Principal Investigator: Mariela Bernabe-Garcia, PhD Instituto Mexicano del Seguro Social

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Responsible Party: Coordinación de Investigación en Salud, Mexico
ClinicalTrials.gov Identifier: NCT04031508     History of Changes
Other Study ID Numbers: R-2017-3603-19
First Posted: July 24, 2019    Key Record Dates
Last Update Posted: July 24, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Coordinación de Investigación en Salud, Mexico:
PPHN
Diaphragmatic Hernia
omega 3
DHA and EPA
Additional relevant MeSH terms:
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Hypertension, Pulmonary
Hypertension
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases