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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-004946-41 | EudraCT Number |
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| Name | Class |
|---|---|
| Azienda Ospedaliera di Padova | OTHER |
| Hospital Universitario La Paz | OTHER |
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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.
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:
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Personalized-Parenteral Nutrition (P-PN) | Active Comparator | 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:
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. |
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| Standardized-Parenteral Nutrition (S-PN) | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Standardized-parenteral nutrition (S-PN) | Drug | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| WEIGHT CHANGE | Daily weight change (g/kg/d) during parenteral nutrition (PN) | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| MUSCLE ULTRASOUND (optional) | Ultrasound measurement of mid thigh and mid arm muscle thickness (cm). | At the start of PN, after 7, 14 and 28 days (+-1 d). |
| ADIPOSE TISSUE ULTRASOUND (optional) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Virgilio P Carnielli, MD, PhD | Contact | +39 071 596 2045 | v.carnielli@univpm.it | |
| Alessio Correani, MSc, PHD | Contact | +39 071 596 2888 | alessio.correani@gmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ospedali Riuniti Ancona | Recruiting | Ancona | 60123 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16585322 | Background | Ehrenkranz RA, Dusick AM, Vohr BR, Wright LL, Wrage LA, Poole WK. Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants. Pediatrics. 2006 Apr;117(4):1253-61. doi: 10.1542/peds.2005-1368. | |
| 28270894 | Background | Evering VH, Andriessen P, Duijsters CE, Brogtrop J, Derijks LJ. The Effect of Individualized Versus Standardized Parenteral Nutrition on Body Weight in Very Preterm Infants. J Clin Med Res. 2017 Apr;9(4):339-344. doi: 10.14740/jocmr2893w. Epub 2017 Feb 21. |
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| ID | Term |
|---|---|
| D047928 | Premature Birth |
| D006963 | Hyperphagia |
| ID | Term |
|---|---|
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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Patients/Parents/Legal guardian will be masked. The statistician will be also masked when analyzing the data.
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| Personalized-parenteral nutrition (P-PN) | Drug | 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. |
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Ultrasound measurement of mid thigh and mid arm adipose tissue thickness (cm).
| At the start of PN, after 7, 14 and 28 days (+-1 d). |
| BONE ULTRASOUND (optional) | Metacarpus speed of sound (m/s) and metacarpus bone transmission time (ms). | At the start of PN, after 7, 14 and 28 days (+-1 d). |
| WEIGHT | Weight measured by a digital infant scale (grams) | Daily up to 42 weeks of post menstrual age or discharge if it comes first. |
| TOTAL BODY LENGTH | Total body length measured by a neonatal stadiometer (cm) | Weekly up to 42 weeks of post menstrual age or discharge if it comes first. |
| HEAD CIRCUMFERENCE | Head circumference measured by a flexible non-stretchable tape (cm) | Weekly up to 42 weeks of post menstrual age or discharge if it comes first. |
| GLUCIDE TOLERANCE | Blood glycemia (mg/dl). | Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). |
| AMINO ACID TOLERANCE | Plasma and urinary urea concentrations (mg/dl). | 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). |
| TRIGLYCERIDE CONCENTRATION | Plasma triglycerides (TG; mg/dl). | 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). |
| FATTY ACID CONCENTRATION (optional) | Plasma fatty acid concentration (FA; mg/dl). | At PN day 7 (+-1 d). |
| DICARBOXYLIC AND HYDROXYL FATTY ACID CONCENTRATION (optional) | Urinary dicarboxylic acids (DCA; mmol/mol creatinine) and hydroxyl fatty acids (H-FA; mmol/mol creatinine). | At PN day 7 (+-1 d). |
| ELECTROLYTE CONCENTRATION | Hemogasanalysis (Na+, mmol/l; K+, mmol/l; Ca2+, mg/dl; Cl-, mmol/l) and SBE (standard base excess, mmol/L) | Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). |
| HYPER AND HYPO-NATREMIA, -KALEMIA, -CHLOREMIA, -PHOSPHATEMIA, -CALCEMIA, AND -PARATHYROIDISM | Episodes of Hyper/Hypo Natremia, -KaIemia, -Chloremia, -Phosphatemia, -Calcemia, and -Parathyroidism (number). | Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). |
| METABOLIC ACIDOSIS | SBE < -7.5 mmol/L. | Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). |
| BONE MINERALIZATION-1: CALCIUM and PHOSPHORUS CONCENTRATIONS | Plasma and urinary calcium and phosphorus concentrations (mg/dl). | 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. |
| LIVER FUNCTION: ALP, AST, ALT AND GGT CONCENTRATIONS | Plasma alkaline phosphatase (ALP; UI/L), aspartate transaminase (AST; UI/L), alanine transaminase (ALT; UI/L), and gamma-glutamyl transpeptidase (GGT, UI/L). | 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. |
| BONE MINERALIZATION-2: PTH CONCENTRATIONS | Plasma parathormone concentrations (PTH; pg/ml). | 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. |
| BONE MINERALIZATION: PYD, PICP and ICTP CONCENTRATION (optional) | 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) | At the start of PN and at PN day 28 (+-1 d) (endpoint). |
| BILIRUBIN CONCENTRATION | Plasma bilirubin (total and conjugated; mg/dl) | 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. |
| MORBIDITY - 1 | 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). | Up to 42 weeks of post menstrual age or discharge if it comes first. |
| MORBIDITY - 2 | The incidence of Cholestasis and Renal and Hepatic Insufficiency. | Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). |
| MORTALITY BEFORE 42 WEEKS POST MENSTRUAL AGE | Death before 42 weeks post menstrual age (number). | At 42 weeks of post menstrual age or discharge if it comes first. |
| MORTALITY DURING PARENTERAL NUTRITION | Death during PN (number). | From the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). |
| ENTERAL NUTRITION INTAKES | Enteral nutrition intakes (ml/kg). | Daily from the start of PN to day 28 of life. |
| PARENTERAL NUTRITION INTAKES: AMINO ACIDS | Intravenous amino acid intakes (g/kg). | Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). |
| PARENTERAL NUTRITION INTAKES: LIPIDS | Intravenous lipid intakes (g/kg). | Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). |
| PARENTERAL NUTRITION INTAKES: GLUCOSE | Intravenous glucose intakes (g/kg). | Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). |
| PARENTERAL NUTRITION DURATION | PN duration (days). | Daily from the start to the stop of PN (endpoint: PN day 28 if PN duration >28 days). |
| MECHANICAL VENTILATION | Mechanical ventilation duration and oxygen therapy duration (days). | Up to 42 weeks of post menstrual age or discharge if it comes first. |
| DRUG THERAPIES | Drug therapy duration (hours). | Up to 42 weeks of post menstrual age or discharge if it comes first. |
| PHARMACOECONOMICS | Healthcare costs (euro). | Up to 42 weeks of post menstrual age or discharge if it comes first. |
| METABOLIC COMPLICATIONS | 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). | Up to 42 weeks of post menstrual age or discharge if it comes first. |
| Azienda Ospedaliera di Padova | Recruiting | Padova | Italy |
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| Hospital Universitario La Paz | Recruiting | Madrid | Spain |
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| 20234142 | Background | Smolkin T, Diab G, Shohat I, Jubran H, Blazer S, Rozen GS, Makhoul IR. Standardized versus individualized parenteral nutrition in very low birth weight infants: a comparative study. Neonatology. 2010;98(2):170-8. doi: 10.1159/000282174. Epub 2010 Mar 16. |
| 6794364 | Background | Dice JE, Burckart GJ, Woo JT, Helms RA. Standardized versus pharmacist-monitored individualized parenteral nutrition in low-birth-weight infants. Am J Hosp Pharm. 1981 Oct;38(10):1487-9. |
| 14629529 | Background | Yeung MY, Smyth JP, Maheshwari R, Shah S. Evaluation of standardized versus individualized total parenteral nutrition regime for neonates less than 33 weeks gestation. J Paediatr Child Health. 2003 Nov;39(8):613-7. doi: 10.1046/j.1440-1754.2003.00246.x. |
| 111548 | Background | Mutchie KD, Smith KA, MacKay MW, Marsh C, Juluson D. Pharmacist monitoring of parenteral nutrition: clinical and cost effectiveness. Am J Hosp Pharm. 1979 Jun;36(6):785-7. |
| 25655621 | Background | Kreissl A, Repa A, Binder C, Thanhaeuser M, Jilma B, Berger A, Haiden N. Clinical Experience With Numeta in Preterm Infants: Impact on Nutrient Intake and Costs. JPEN J Parenter Enteral Nutr. 2016 May;40(4):536-42. doi: 10.1177/0148607115569733. Epub 2015 Feb 5. |
| 8890070 | Background | Namgung R, Tsang RC, Sierra RI, Ho ML. Normal serum indices of bone collagen biosynthesis and degradation in small for gestational age infants. J Pediatr Gastroenterol Nutr. 1996 Oct;23(3):224-8. doi: 10.1097/00005176-199610000-00004. |
| 11092513 | Background | Rossi L, Branca F, Cianfarani S. Collagen cross-links and early postnatal growth in newborns with intrauterine growth retardation. Metabolism. 2000 Nov;49(11):1467-72. doi: 10.1053/meta.2000.17670. |
| 3104873 | Background | Jones PJ, Winthrop AL, Schoeller DA, Swyer PR, Smith J, Filler RM, Heim T. Validation of doubly labeled water for assessing energy expenditure in infants. Pediatr Res. 1987 Mar;21(3):242-6. doi: 10.1203/00006450-198703000-00007. |
| 3085521 | Background | Schoeller DA, Ravussin E, Schutz Y, Acheson KJ, Baertschi P, Jequier E. Energy expenditure by doubly labeled water: validation in humans and proposed calculation. Am J Physiol. 1986 May;250(5 Pt 2):R823-30. doi: 10.1152/ajpregu.1986.250.5.R823. |
| 7986782 | Background | van Marken Lichtenbelt WD, Westerterp KR, Wouters L. Deuterium dilution as a method for determining total body water: effect of test protocol and sampling time. Br J Nutr. 1994 Oct;72(4):491-7. doi: 10.1079/bjn19940053. |
| D000091642 | Urogenital Diseases |
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |