Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612000823875
Ethics application status
Approved
Date submitted
10/07/2012
Date registered
6/08/2012
Date last updated
8/03/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
Zinc supplementation in very low birth weight neonates
Scientific title
Zinc supplementation and neonatal morbidity : a randomized, placebo-controlled study in very low birth weight neonates
Secondary ID [1] 280795 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
ZEN (Zinc Efficacy in Neonates)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Morbidity in very low birth weight neonates 286853 0
sepsis 286872 0
Necrotizing enterocolitis 287050 0
Bronchopulmonary dysplasia 287051 0
Intraventricular hemorrhage 287052 0
Retinopathy of prematurity 287053 0
Condition category
Condition code
Diet and Nutrition 287181 287181 0 0
Other diet and nutrition disorders
Reproductive Health and Childbirth 287380 287380 0 0
Complications of newborn
Oral and Gastrointestinal 287381 287381 0 0
Normal oral and gastrointestinal development and function

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Active treatment consist in zinc at dosage of 10 mg/d associated to other vitamins. We used commercial zinc preparation available on the market as drops. Treatment was started at 7 d of life until discharge from the hospital. Other vitamins contained in the preparation were (pro dose)folates (120 mcg), vit. B12 (0.6 mcg) and Vit D3 (400 UI), vit. C (60 mg), vit. E (6 mg), vit. A (480 mcg). To reach Recommended Dietary Allowance (RDA) for folates, vit. B12, D3, C, E, A, and B group, all subjects were supplemented daily with folates (56 mcg/Kg), vit B12 (0.3 mcg/Kg), vit. D3 (10 UI/Kg), vit. C (25 mg/Kg), E (2.8 mg/Kg), A (500 mcg/Kg), and B group (B1 0.35 mg/Kg, B2 0.15 mg/Kg, B6 0.18 mg/Kg, niacin 6.8 mg/Kg, and biotin 6 mcg) intravenously when in parenteral nutrition. When full enteral feeding was achieved the RDA for folates, vit B12, vit. D3, vit. C, E, A, and B group were reached in all subjects considering that preterm formula used during the study contained folates (30 mcg), vit B12 (0.2 mcg), vit. D3 (10 UI), vit. C (20 mg/Kg), E (2.4 mg), A (180 mcg), and B group (B1 0.19 mg/Kg, B2 0.30 mg/Kg, B6 0.135 mg/Kg, niacin 1.1 mg/Kg, and biotin 5.5 mcg) per 100 ml, and that all subject were supplemented daily with vit D3 (400 UI) per os. In this way, RDA for zinc was obtained only in the active treatment group.
Intervention code [1] 285227 0
Prevention
Intervention code [2] 285228 0
Treatment: Drugs
Comparator / control treatment
Placebo consist in a multivitamins complex not containing zinc. We used a commercial preparation, available on the market as drops, composed by folates (120 mcg), vit. B12 (0.6 mcg) and vit. D3 (400 UI), vit. C (38 mg), vit. E (3 mg), vit. A (375 mcg).
To reach Recommended Dietary Allowance (RDA) for folates, vit. B12, D3, C, E, A, and B group, all subjects were supplemented daily with folates (56 mcg/Kg), vit B12 (0.3 mcg/Kg), vit. D3 (10 UI/Kg), vit. C (25 mg/Kg), E (2.8 mg/Kg), A (500 mcg/Kg), and B group (B1 0.35 mg/Kg, B2 0.15 mg/Kg, B6 0.18 mg/Kg, niacin 6.8 mg/Kg, and biotin 6 mcg) intravenously when in parenteral nutrition. When full enteral feeding was achieved the RDA for folates, vit B12, vit. D3, vit. C, E, A, and B group were reached in all subjects considering that preterm formula used during the study contained folates (30 mcg), vit B12 (0.2 mcg), vit. D3 (10 UI), vit. C (20 mg/Kg), E (2.4 mg), A (180 mcg), and B group (B1 0.19 mg/Kg, B2 0.30 mg/Kg, B6 0.135 mg/Kg, niacin 1.1 mg/Kg, and biotin 5.5 mcg) per 100 ml, and that all subject were supplemented daily with vit D3 (400 UI) per os. In this way, RDA for zinc was obtained only in the active treatment group.
Control group
Placebo

Outcomes
Primary outcome [1] 287477 0
The morbidity of very low birth weight newborns treated with zinc. Morbidity was defined by the presence of at least one of the following conditions: BPD, IVH, NEC, sepsis, and ROP
Timepoint [1] 287477 0
Morbidity of neonates during hospitalization
Secondary outcome [1] 298254 0
mortality
Timepoint [1] 298254 0
Mortality of neonates during hospitalization

Eligibility
Key inclusion criteria
Newborns with birth weight 401-1500 g or gestational age 24-32 weeks, consecutively observed in Neonatal Intensive Care Units
Minimum age
1 Weeks
Maximum age
4 Weeks
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
congenital or maternal infections, immunodeficiency, malformations, syndrome, genetic defects, evidence of infections and NEC before enrolment, critically ill condition (blood pH < 6.8, or hypoxia with persistent bradycardia for at least 1 hour), and hospitalization less than 1 week

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Enrolled subject were randomly allocated to “active treatment” consisting in zinc at dosage of 10 mg/d associated to other vitamins, or to “placebo” consisting in a similar multivitamins complex not containing zinc. We used two commercial zinc preparations available on the market as drops, with similar packaging. The two multivitaminic formulations were placed in 10 mL bottles (one per neonate), labeled with a specific code corresponding to a code reported in the randomization list. Group assignment was concealed until statistical analysis was completed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated randomization list
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/02/2009
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment outside Australia
Country [1] 4395 0
Italy
State/province [1] 4395 0

Funding & Sponsors
Funding source category [1] 285593 0
Hospital
Name [1] 285593 0
V.Betania Evangelic Hospital of Naples
Country [1] 285593 0
Italy
Primary sponsor type
Hospital
Name
“V.Betania” Evangelic Hospital of Naples
Address
Via Argine 651,
80147,
Naples
Country
Italy
Secondary sponsor category [1] 284422 0
None
Name [1] 284422 0
Address [1] 284422 0
Country [1] 284422 0
Other collaborator category [1] 276923 0
University
Name [1] 276923 0
University of Naples Federico II
Address [1] 276923 0
via Pansini 5,
80131
Naples
Country [1] 276923 0
Italy

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287606 0
V. Betania Ethic Committee
Ethics committee address [1] 287606 0
Via Argine 651,
80147,
Naples
Ethics committee country [1] 287606 0
Italy
Date submitted for ethics approval [1] 287606 0
03/01/2009
Approval date [1] 287606 0
30/01/2009
Ethics approval number [1] 287606 0
0901

Summary
Brief summary
There are many evidences that zinc may be essential for brain, pulmonary and intestinal development and function, as well as for growth, in the fetus and child. Preterm infants have a high risk of zinc deficiency. In this study we will aimed to investigate the efficacy of zinc supplementation in reducing morbidity of preterm neonates related to neurological, respiratory and intestinal complications.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34406 0
Gianluca Terrin
Address 34406 0
Dipartimento Scienze Ginecologiche-Ostetriche e Scienze Urologiche Universita di Roma La Sapienza viale Regina Elena 285 00198, Rome, Italy
Country 34406 0
Italy
Phone 34406 0
3339191207
Fax 34406 0
Email 34406 0
[email protected]
Contact person for public queries
Name 17653 0
Prof Gianluca Terrin
Address 17653 0
Dipartimento Scienze Ginecologiche-Ostetriche e Scienze Urologiche
Universita di Roma La Sapienza
viale Regina Elena 285
00198, Rome, Italy
Country 17653 0
Italy
Phone 17653 0
+39 06 499 72521
Fax 17653 0
+39 0633776660
Email 17653 0
[email protected]
Contact person for scientific queries
Name 8581 0
Prof Gianluca Terrin
Address 8581 0
Dipartimento Scienze Ginecologiche-Ostetriche e Scienze Urologiche
Universita di Roma La Sapienza
viale Regina Elena 285
00198, Rome, Italy
Country 8581 0
Italy
Phone 8581 0
+39 06 499 72521
Fax 8581 0
+39 0633776660
Email 8581 0
[email protected]

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