To evaluate the safety, tolerability, protein accretion, amino acid plasma levels and long-term outcome of Neoven compared to Vaminolact in preterm infants with a birth weight from 800 g to less than 1500 g and with a gestational age from 25 weeks…
ID
Source
Brief title
Condition
- Protein and amino acid metabolism disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
a) Hyperammonemia
b) Metabolic acidosis
c) Azotemia
d) Hyperaminoacidemia
e) Hyperglycemia
Secondary outcome
a) Anthropometry (weight, crown-heel length, head circumference)
b) Time to full enteral feeding defined as > 120 ml / kg / day
c) Length of ICU stay
d) Mortality rate
e) Adverse events
f) Infection rate including sepsis, for definition see appendix 3
g) Incidence of Necrotising Enterocolitis (NEC), BELL stage > grade II defined
by Bell et al 1978
h) Incidence of Broncho-Pulmonary Dysplasia (BPD) at 28 days and at 36 weeks of
corrected age as defined in appendix 7
(Jobe et al 2001)
i) Amino acid profiles
j) Mental and psychometric assessments including audiometry for otological
disorders evaluation
k) Incidence of visual disorders especially fundoscopy for retinopathies,
retinopathy of prematurity > grade III
Background summary
This study should give information on the safety, tolerability, protein
accretion, amino acid plasma levels and long-term outcome of Neoven compared to
Vaminolact in premature very low birth weight (VLBW) infants.
The main focus of the study will be to examine a variety of laboratory
parameters evaluating azotemia, metabolic acidosis, hyperammonemia,
hyperaminoacidemia and hyperglycemia. The secondary variables are important for
both evaluation and comparison of the clinical condition of the patients and
can be regarded as related to the administration of amino acids.
Vaminolact has been chosen as comparator not only in this trial but in all
currently planned clinical trials with Neoven. Vaminolact is a well-established
paediatric AA solution in many countries and it will help to standardise the
overall safety evaluation of Neoven. At the end of the clinical development
program, the data obtained from all Neoven trials will be pooled within an
Overall Safety Analysis (OSA). In addition, as Neoven has compositional
similarities to Vaminolact (e.g. mostly identical composition of essential
AAs), the proof-of-concept of new compositional design elements (e.g.
glutamine) can be better evaluated.
Dosing principles * start dose, staggering and full-dose as well as daily
continuous infusion over at least 20 hours/day * are in accordance with
accepted guidelines on nutrition and the clinical routine of the
investigational sites.
Study objective
To evaluate the safety, tolerability, protein accretion, amino acid plasma
levels and long-term outcome of Neoven compared to Vaminolact in preterm
infants with a birth weight from 800 g to less than 1500 g and with a
gestational age from 25 weeks to less than 32 weeks
Study design
see page 16 of protocol : study schedules
Intervention
Investigational drug: Neoven (a 10% paediatric amino acid solution for
intravenous infusion in parenteral nutrition)
Control drug: Vaminolact (a 6.5% paediatric amino acid solution for intravenous
infusion in parenteral nutrition)
Dosage: 1.0 - 2.0 g AA/kg bw/d on day 1 of life*
1.5 - 2.5 g AA/kg bw/d on day 2 of life*
2.0 - 3.0 g AA/kg bw/d on day 3-5 of life*
as clinically needed on day 6-28 of life
* In case treatment with study drug starts on day 2 of life and the dosage of
1.5 g AA/kg bw/day is too high in the Investigator*s opinion the dosage regimen
can refer to days of treatment instead of days of life, thus the Investigator
can start with the lowest dosage of 1.0 g AA/kg bw/d on day 2.
Infusion time: At least 20 hours per day
Duration of Infusion: At least 5 consecutive days, infusion may continue if
required until patient*s discharge for a maximum of 28 days.
Study burden and risks
The blood samples, which will be taken during this study may cause discomfort,
pain and/or bruising. When a needle is placed in the skin and vein to
take blood, there is a very small chance that an infection may occur.
All medicines may have side effects. A very limited number of side effects have
been seen with the type of amino acid liquid which will be used in the study.
Reactions that may occur because of the solution or the way it is given include
fever, venous thrombosis or phlebitis, extravasation and hypervolemia.
Borkenberg 14
61440 Oberursel
Germany
Borkenberg 14
61440 Oberursel
Germany
Listed location countries
Age
Inclusion criteria
a) Sex: Male or female
b) Birth weight: 800 g - less than 1500 g
c) Gestational age: 250/7 - 316/7 weeks
d) Age: < 48 hours after birth
e) Life expectation should be at least 5 days as of start of PN
f) Estimated requirement of parenteral nutrition (PN) including amino acids for at least 5 days
g) Legal representative(s) signed and dated Informed Consent
Exclusion criteria
a) Severe congenital malformations [like gastroschisis, omphalocele, a syndrome associated with (suspected) chromosomal anomalies, severe hydrops fetalis]
b) Insufficient renal function with serum creatinine of * 2.0 mg/dl (* 120 µmol/L) or receiving dialysis/hemofiltration therapy.
c) Severe liver dysfunction with either ammonia levels >150 *mol/l or direct bilirubin > 8 mg/dl and ALT >200 IU/l
d) Severe congenital heart disease
e) Haematolytic disease and hyperbilirubinemia requiring exchange infusion
f) Oxygen saturation SpO2 < 80% for longer than two hours
g) Severe thrombocytopenia: platelets < 30x109/L
h) Administration of catecholamines except
- low dose dopamine * 10 µg/kg bw/min and/or
- dobutamine * 10 µg/kg bw/min or
- adrenaline * 0.2 µg/kg bw/min
i) Congenital metabolic and/or endocrinologic disorders that affect energy and nutrient metabolism (e.g. errors of amino acid metabolism)
j) Severe metabolic acidosis (pH < 6.9 and base excess (BE < -15 mmol/L) after 6 hours of life
k) Oral/enteral nutrition with more than 20% of total energy intake at the beginning of amino acid supplementation
l) Participation in another interventional clinical trial since birth
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-012602-39-NL |
| CCMO | NL31506.029.10 |