Condition category
Eye Diseases
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Retinopathy of prematurity is a disease that occurs in premature babies where abnormal blood vessels grow in the retina (the layer of nerve tissue in the eye). This growth can cause the retina to detach from the back of the eye, causing blindness. The aim of this study is to find out whether lutein and zeaxanthin supplements can prevent retinopathy of prematurity in preterm infants.

Who can participate?
Preterm infants (gestational age 32 weeks or less)

What does the study involve?
Participants are randomly allocated to receive a daily dose of lutein and zeaxanthin or a placebo (dummy drug) until discharged from hospital. The occurrence of retinopathy of prematurity is recorded in both groups to see whether the supplement prevents retinopathy of prematurity.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Careggi University Hospital of Florence (Italy)

When is the study starting and how long is it expected to run for?
February 2008 to February 2011

Who is funding the study?
SOOFT Italia S.p.a. (Italy)

Who is the main contact?
Prof. Carlo Dani

Trial website

Contact information



Primary contact

Prof Carlo Dani


Contact details

Division of Neonatology
Careggi University Hospital of Florence
Largo Brambilla 3

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

LUtein and zeaxanthin SUpplementation in Preterm infants to prevent RetinOpathy of Prematurity: a multicentre prospective randomised double-blind placebo-controlled study



Study hypothesis

Retinopathy of prematurity (ROP) that was classified according to the International Classification as follows:
Stage 1, a thin demarcation line separates the avascular retina anteriorly from the vascularized retina posteriorly
Stage 2, a ridge arises in the region of the demarcation line and extends above the plane of the retina
Stage 3, neovascularization extends from the ridge into the vitreous
Stage 4, there is partial retinal detachment; stage 5, there is total retinal detachment
Moreover, increased venous dilation and arteriolar tortuosity are markers of severe active ROP and are referred to as plus disease.

Lutein and zeaxanthin supplementation may decrease the occurrence of retinopathy of prematurity (ROP) in high risk preterm infants.

Ethics approval

Ethics Committee for Clinical Trials of Medicines, University Hospital Careggi (Comitato Eitco per la sperimentazione clinica dei medicinali, Azienda ospedaliera Universitaria Careggi), 25/05/2007, ref: 38/2009

Study design

Multicentre prospective randomised double-blind placebo-controlled study

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet


Retinopathy of prematurity (ROP)


Infants at each unit were grouped in blocks:
1. 1st block: gestational age < 25+6 weeks
2. 2nd block: gestational age from 26+0 to 28+6 weeks
3. 3rd block: gestational age > 29+0 weeks)

Infants were randomly assigned to a treatment group using the sealed envelope technique which were prepared at Careggi University Hospital of Florence and then distributed to participating centres. Each infant received a daily oral dose of 0.5 ml containing 0.14 mg of lutein and 0.006 mg of zeaxanthin (LUTEINofta®, Sooft Italia, Montegiorgio, Italy) or indistinguishable placebo. Supplementation was begun from the 1st to the 7th day of life and was given until discharge. Lutein/Zeaxanthin (L/Z) or placebo were given before feeding or added to breast milk (from the infant’'s mother or a donor) or to infant formula. Age and duration of supplementation were recorded. Time of initial feeding, use of breast milk or preterm infant formula, and change from preterm infant formula to term infant formula were at the discretion of the attending physician.

Intervention type



Not Applicable

Drug names

Primary outcome measure

1. The successful rate of lutein and zeaxanthin supplementation at preventing ROP
2. The rate of primary endpoint was calculated on the basis of collected data and in agreement with those from literature, while the duration of follow up was decided on the basis of recommendation of the Italian Society of Neonatology and in agreement with the current literature

Secondary outcome measures

1. Gestational and post-natal age at ROP diagnosis
2. The need for surgical treatment (laser- or cryo-therapy)
3. The incidence of sepsis, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC) and mortality

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

Infants with gestational age < 32 weeks after parental informed consent

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. The presence of major congenital malformation
2. Fetal hydrops
3. Death before the first ophthalmologic examination
3. Lack of lutein supplementation > 10 days during the first 30 days of life
4. Development of aggressive-posterior ROP (AP-ROP)

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

Careggi University Hospital of Florence

Sponsor information


University of Florence (Italy)

Sponsor details

Department of Surgical and Medical Critical Care
Viale Morgagni 85

Sponsor type




Funder type


Funder name

SOOFT Italia S.p.a. (Italy)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

2012 results in:

Publication citations

  1. Results

    Dani C, Lori I, Favelli F, Frosini S, Messner H, Wanker P, De Marini S, Oretti C, Boldrini A, Massimiliano C, Bragetti P, Germini C, Lutein and zeaxanthin supplementation in preterm infants to prevent retinopathy of prematurity: a randomized controlled study., J. Matern. Fetal. Neonatal. Med., 2012, 25, 5, 523-527, doi: 10.3109/14767058.2011.629252.

Additional files

Editorial Notes

23/05/2017: Plain English summary added.