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Personalized vs Standardized PN for Preterm Infants >1250g

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ClinicalTrials.gov Identifier: NCT03693287
Recruitment Status : Not yet recruiting
First Posted : October 2, 2018
Last Update Posted : February 5, 2020
Sponsor:
Collaborators:
Azienda Ospedaliera di Padova
Hospital Universitario La Paz
Information provided by (Responsible Party):
Virgilio Paolo Carnielli, Ospedali Riuniti Ancona

Brief Summary:
Preterm infants (gestational age between 189 and 258 days) with a birth weight (BW) greater than 1250 grams will be randomized to personalized-parenteral nutrition (P-PN) or standardized-parenteral nutrition (S-PN). The aim of the study is to evaluate the effect of S-PN versus P-PN on growth of preterm infants with BW>1250 grams.

Condition or disease Intervention/treatment Phase
Infant,Premature Parenteral Nutrition Growth Drug: Standardized-parenteral nutrition (S-PN) Drug: Personalized-parenteral nutrition (P-PN) Phase 4

Detailed Description:

Parenteral nutrition (PN) is a crucial part of the clinical care of preterm infants. Traditionally different components of PN are prescribed individually considering requirements of an individual infant (P-PN). Recently, standardized PN formulations (S-PN) for preterm infants have been assessed and may have advantages including a better provision of nutrients, less prescription and administration errors, decreased risk of infection, and cost savings. The recent introduction of triple-chamber bags that provides total nutrient admixture for infants may have the additional advantage of decreased risk of contamination and ease of administration.

The proposed intervention and hypothesis: The investigators propose a multi-centered Phase IV RCT to compare S-PN versus P-PN, that is the usual care for preterm infants with a birth weight >1250 grams requiring PN in the intensive care units involved in the study. The investigators hypothesize that weight gain during PN of preterm infants with a BW greater than 1250 grams who received S-PN is not statically inferior (< 2g/kg/d) to that of infants who received P-PN (Non-inferiority study).

Study design: Preterm infants (gestational age between 189 and 258 days) with a BW greater than 1250 grams will be enrolled during hospitalization after the informed consent is drawn from parents or legal guardians. All infants will undergo a physical examination and the need of PN will be judged by the caring physician according to predefined criteria. Infants requiring PN will be divided into 3 clinical groups:

  • Group A or EARLY HIGH-RISK INFANTS: these infants present in rather severe conditions at birth or soon after birth which make enteral nutrition (EN) impossible or non-desirable. In this group of infants, the investigators will include patients with Perinatal asphyxia, Perinatal shock (Cardiovascular or Septic), GI malformations, Severe Intra-uterine growth retardation (IUGR) with markedly abnormal prenatal doppler, and Miscellanea. These infants will have a central venous access soon after birth.
  • Group B or INSUFFICIENT EN INTAKE: these Infants are in rather stable conditions after birth, however these infants may exhibit gastrointestinal (GI) intolerance of any origin. These patients will be randomized after 72 hours of life if the mean EN volume of the first 72-hrs of life will be less than 30 ml/kg/d or if EN intake on the third day will be less than 45 ml/kg/d. In this category, the investigators will include also those infants who will have their EN intake reduced below 30 ml/kg for 3 consecutive days (usually from day 3 through day 6) because of PDA treatment. These infants will have a central venous access inserted on the 3rd or 4th day of life if not already in place.
  • Group C or LATE SICKNESS: these are the infants that experience a major sickness after a variable period of good gastrointestinal tolerance. In this group, the investigators will have infants with Necrotizing Enterocolitis (NEC), Severe Sepsis with abdominal distension and poor peristalsis, Septic Shock, or other severe unexpected conditions such as volvulus etc. These infants will also have a central venous access.

Study infants within each clinical group will be divided into 2 blocks on the basis of their BW: 1250-1750 g (Block A) e >1750 g (Block B). Infants of each study group will be then randomly assigned to P-PN or S-PN (Intervention-arm). The study PN bags will be used until the study infants will not be able to tolerate 135 ml/kg/d enterally (range: 120-160 ml/kg/d according to the local practice) or until day 28 of PN (after the 28th day of PN, patients will receive PN according to the normal clinical practice).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Masking Description: Patients/Parents/Legal guardian will be masked. The statistician will be also masked when analyzing the data.
Primary Purpose: Treatment
Official Title: Personalized Versus Standardized Parenteral Nutrition for Preterm Infants With a Birth Weight Greater Than 1250 Grams: a Multicenter Randomized Phase IV Clinical Trial
Estimated Study Start Date : February 15, 2020
Estimated Primary Completion Date : March 31, 2022
Estimated Study Completion Date : June 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Body Weight

Arm Intervention/treatment
Active Comparator: Personalized-Parenteral Nutrition (P-PN)

These patients will receive personalized parenteral nutrition (PN) as it is customary in the participating centers.

Dosing range: glucose from 9 to 13 g/kg/d, AA from 2.0 to 3.0 g/kg/d, and FAT from 1.5 to 2.5 g/kg/d.

Intravenous macronutrient intakes:

  • PN day 1: 2.0 g/kg of AA, 1.6 g/kg of FAT and 9 g/kg of glucides.
  • PN day 2: 2.5 g/kg of AA, 2.0 g/kg of FAT and 11 g/kg of glucides.
  • PN day 3 and the days after: 3.0 g/kg of AA, 2.5 g/kg of FAT and 13 g/kg of glucides.

Intravenous vitamins will be supplied according to local clinical practice. Variations in macronutrient intakes will be tolerated within ±20%.

Nutritional goal: to ensure at least 2.5 g/kg/d of AA and 70 kcal/kg/d of no protein energy (NPE) from PN day 2.

Drug: Personalized-parenteral nutrition (P-PN)

Intravenous glucose will be "dextrose 50%", amino acids (AA) will be "Primene®" and lipids (FAT) will be "Clinoleic®".

Parenteral nutrition bags will be prepared by the hospital pharmacy according to the prescription of the attending neonatologist.


Experimental: Standardized-Parenteral Nutrition (S-PN)

These patients will receive standardized parenteral nutrition (PN) by using a triple chamber bag (Numeta G13%E®).

Dosing range: 80-300 ml/d. Intravenous macronutrient intakes: 65 ml/kg at PN day 1, 80 ml/kg at PN day 2 and then 100 ml/kg from PN day 3.

Nutritional goal: to ensure at least 2.5 g/kg/d of amino acids (AA) and 70 kcal/kg/d of no protein energy (NPE) from PN day 2.

Drug: Standardized-parenteral nutrition (S-PN)
NUMETA G13%E 300 mL is a triple-chamber (lipid emulsion, amino acids solution with electrolytes, and glucose solution), ready-to-use parenteral nutrition product available to treat preterm infants (less than 37 weeks gestational age).




Primary Outcome Measures :
  1. WEIGHT CHANGE [ Time Frame: From the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). At least 7 days of PN will be required to calculate weight gain during PN. ]
    Daily weight change (g/kg/d) during parenteral nutrition (PN)


Secondary Outcome Measures :
  1. MUSCLE ULTRASOUND (optional) [ Time Frame: At the start of PN, after 7, 14 and 28 days (+-1 d). ]
    Ultrasound measurement of mid thigh and mid arm muscle thickness (cm).

  2. ADIPOSE TISSUE ULTRASOUND (optional) [ Time Frame: At the start of PN, after 7, 14 and 28 days (+-1 d). ]
    Ultrasound measurement of mid thigh and mid arm adipose tissue thickness (cm).

  3. BONE ULTRASOUND (optional) [ Time Frame: At the start of PN, after 7, 14 and 28 days (+-1 d). ]
    Metacarpus speed of sound (m/s) and metacarpus bone transmission time (ms).

  4. WEIGHT [ Time Frame: Daily up to 42 weeks of post menstrual age or discharge if it comes first. ]
    Weight measured by a digital infant scale (grams)

  5. TOTAL BODY LENGTH [ Time Frame: Weekly up to 42 weeks of post menstrual age or discharge if it comes first. ]
    Total body length measured by a neonatal stadiometer (cm)

  6. HEAD CIRCUMFERENCE [ Time Frame: Weekly up to 42 weeks of post menstrual age or discharge if it comes first. ]
    Head circumference measured by a flexible non-stretchable tape (cm)

  7. GLUCIDE TOLERANCE [ Time Frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). ]
    Blood glycemia (mg/dl).

  8. AMINO ACID TOLERANCE [ Time Frame: At the start of PN, at PN day 7 (+-1 d) and 14 (+-1 d), and then every 2 weeks until the stop of PN (endpoint: PN day 28 if PN duration >28 days). ]
    Plasma and urinary urea concentrations (mg/dl).

  9. TRIGLYCERIDE CONCENTRATION [ Time Frame: At PN day 3 (+-1 d) and 7(+-1 d), and then every 7 days (+-1 d) until the stop of PN (endpoint: PN day 28 if PN duration >28 days). ]
    Plasma triglycerides (TG; mg/dl).

  10. FATTY ACID CONCENTRATION (optional) [ Time Frame: At PN day 7 (+-1 d). ]
    Plasma fatty acid concentration (FA; mg/dl).

  11. DICARBOXYLIC AND HYDROXYL FATTY ACID CONCENTRATION (optional) [ Time Frame: At PN day 7 (+-1 d). ]
    Urinary dicarboxylic acids (DCA; mmol/mol creatinine) and hydroxyl fatty acids (H-FA; mmol/mol creatinine).

  12. ELECTROLYTE CONCENTRATION [ Time Frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). ]
    Hemogasanalysis (Na+, mmol/l; K+, mmol/l; Ca2+, mg/dl; Cl-, mmol/l) and SBE (standard base excess, mmol/L)

  13. HYPER AND HYPO-NATREMIA, -KALEMIA, -CHLOREMIA, -PHOSPHATEMIA, -CALCEMIA, AND -PARATHYROIDISM [ Time Frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). ]
    Episodes of Hyper/Hypo Natremia, -KaIemia, -Chloremia, -Phosphatemia, -Calcemia, and -Parathyroidism (number).

  14. METABOLIC ACIDOSIS [ Time Frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). ]
    SBE < -7.5 mmol/L.

  15. BONE MINERALIZATION-1: CALCIUM and PHOSPHORUS CONCENTRATIONS [ Time Frame: At the start of PN and at PN day 7 (+-1 d). An additional measurement will be done at PN day 28 (+-1 d) in patients requiring long term PN. ]
    Plasma and urinary calcium and phosphorus concentrations (mg/dl).

  16. LIVER FUNCTION: ALP, AST, ALT AND GGT CONCENTRATIONS [ Time Frame: At the start of PN and at PN day 7 (+-1 d). An additional measurement will be done at PN day 28 (+-1 d) in patients requiring long term PN. ]
    Plasma alkaline phosphatase (ALP; UI/L), aspartate transaminase (AST; UI/L), alanine transaminase (ALT; UI/L), and gamma-glutamyl transpeptidase (GGT, UI/L).

  17. BONE MINERALIZATION-2: PTH CONCENTRATIONS [ Time Frame: At the start of PN and at PN day 7 (+-1 d). An additional measurement will be done at PN day 28 (+-1 d) in patients requiring long term PN. ]
    Plasma parathormone concentrations (PTH; pg/ml).

  18. BONE MINERALIZATION: PYD, PICP and ICTP CONCENTRATION (optional) [ Time Frame: At the start of PN and at PN day 28 (+-1 d) (endpoint). ]
    Urinary pyridinoline crosslinks of collagen (Pyd; nmol/L), serum carboxyterminal propeptide of type I procollagen (PICP; ng/mL) and serum cross-linked carboxyterminal telopeptide of type I collagen (ICTP; ng/mL)

  19. BILIRUBIN CONCENTRATION [ Time Frame: At PN day 7 (+-1 d). An additional measurement will be performed at PN day 14 (+-1 d) in case of PN duration >14 days. ]
    Plasma bilirubin (total and conjugated; mg/dl)

  20. MORBIDITY - 1 [ Time Frame: Up to 42 weeks of post menstrual age or discharge if it comes first. ]
    The incidence of the main complication of prematurity (intraventricular hemorrhage of 3° and 4° grade; Periventricular leukomalacia; Patent ductus arteriosus; Retinopathy of Prematurity; Bronchopulmonary dysplasia and Sepsis).

  21. MORBIDITY - 2 [ Time Frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). ]
    The incidence of Cholestasis and Renal and Hepatic Insufficiency.

  22. MORTALITY BEFORE 42 WEEKS POST MENSTRUAL AGE [ Time Frame: At 42 weeks of post menstrual age or discharge if it comes first. ]
    Death before 42 weeks post menstrual age (number).

  23. MORTALITY DURING PARENTERAL NUTRITION [ Time Frame: From the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). ]
    Death during PN (number).

  24. ENTERAL NUTRITION INTAKES [ Time Frame: Daily from the start of PN to day 28 of life. ]
    Enteral nutrition intakes (ml/kg).

  25. PARENTERAL NUTRITION INTAKES: AMINO ACIDS [ Time Frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). ]
    Intravenous amino acid intakes (g/kg).

  26. PARENTERAL NUTRITION INTAKES: LIPIDS [ Time Frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). ]
    Intravenous lipid intakes (g/kg).

  27. PARENTERAL NUTRITION INTAKES: GLUCOSE [ Time Frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). ]
    Intravenous glucose intakes (g/kg).

  28. PARENTERAL NUTRITION DURATION [ Time Frame: Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). ]
    PN duration (days).

  29. MECHANICAL VENTILATION [ Time Frame: Up to 42 weeks of post menstrual age or discharge if it comes first. ]
    Mechanical ventilation duration and oxygen therapy duration (days).

  30. DRUG THERAPIES [ Time Frame: Up to 42 weeks of post menstrual age or discharge if it comes first. ]
    Drug therapy duration (hours).

  31. PHARMACOECONOMICS [ Time Frame: Up to 42 weeks of post menstrual age or discharge if it comes first. ]
    Healthcare costs (euro).

  32. METABOLIC COMPLICATIONS [ Time Frame: Up to 42 weeks of post menstrual age or discharge if it comes first. ]
    Number of hypertriglyceridemic episodes (plasma triglycerides>265mg/dL), hyperglycemic and hypoglycemic episodes (blood glycaemia>175 mg/dL and <40 mg/dL, respectively) and elevated urea (blood urea>100 mg/dL).



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Ages Eligible for Study:   189 Days to 258 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Birth weight greater than 1250 grams,
  • Gestational age between 189 and 258 days,
  • In need of parenteral nutrition (PN),
  • Signed informed consent by at least one parent or legal guardian.

Exclusion Criteria:

  • Genetic, metabolic, or endocrine disorders diagnosed before/after enrolment
  • Ceftriaxone or Coumarin therapy before/after enrolment,
  • Calcium therapy before enrolment,
  • Cholestasis or hepatic insufficiency before enrolment,
  • Renal insufficiency before enrolment,
  • Hyponatremia before enrolment,
  • Hypertriglyceridemia before enrolment,
  • Hypersensitivity reaction to components of parenteral nutrition before/after enrolment,
  • Off-label use of drug therapy before/after enrolment,
  • Absent informed consent.

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): NCT03693287


Contacts
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Contact: Virgilio P Carnielli, MD, PhD +39 071 596 2045 v.carnielli@univpm.it
Contact: Alessio Correani, MSc, PHD +39 071 596 2888 alessio.correani@gmail.com

Sponsors and Collaborators
Ospedali Riuniti Ancona
Azienda Ospedaliera di Padova
Hospital Universitario La Paz
Publications:

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Responsible Party: Virgilio Paolo Carnielli, Principal Investigator, Ospedali Riuniti Ancona
ClinicalTrials.gov Identifier: NCT03693287    
Other Study ID Numbers: SP-PP18
2018-004946-41 ( EudraCT Number )
First Posted: October 2, 2018    Key Record Dates
Last Update Posted: February 5, 2020
Last Verified: February 2020
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
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Virgilio Paolo Carnielli, Ospedali Riuniti Ancona:
Preterm
Infant
Parenteral Nutrition
Growth
Additional relevant MeSH terms:
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Premature Birth
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications