A Randomised Controlled Trial of Iodide Supplementation in Preterm Infants Follow-up at 2 Years (I2S2)

Study Description

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Brief Summary:

The purpose of this trial is to determine whether iodide supplementation of neonates born under 31 weeks gestation improves neurodevelopment measured at two years of age.

Condition or disease	Intervention/treatment	Phase
Transient Hypothyroxinemia	Drug: sodium iodide; Drug: Sodium Chloride	Phase 4

Detailed Description:

Iodine is essential for the synthesis of thyroxine, and thyroxine is essential for normal brain development in utero and for the first 2-3 years of life. The recommended iodine intake in parenteral nutrition regimens is 1 μg/kg/day and commercially available parenteral solutions for infants reflect these recommendations. In the absence of other iodine sources, infants are vulnerable to negative iodine balance and insufficiency. As many preterm infants are fed parenterally for prolonged periods with solutions which have been shown to be iodine-deficient, the I2S2 Trial was designed as a UK multicentre randomised controlled trial to establish whether iodine supplementation of preterm infants benefits neurodevelopment.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	1275 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Prevention
Official Title:	A Randomised Controlled Trial of Iodide Supplementation in Preterm Infants With Follow-up at 2 Years
Study Start Date :	March 2010
Actual Primary Completion Date :	April 2015
Actual Study Completion Date :	May 2015

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Iodine; This is the hypothetical active arm	Drug: sodium iodide; sodium iodide 30 micrograms/kg/day, daily dose, from randomisation (within 42 hours of birth) to 34 corrected weeks gestation
Placebo Comparator: Placebo; this is the hypothetical placebo	Drug: Sodium Chloride; Sodium Chloride 30 micrograms/kg/day, daily dose, from randomisation (from within 42 hours of birth)to 34 corrected weeks gestation

Outcome Measures

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Primary Outcome Measures :

1. Appreciable neurodevelopmental impairment at 2 years corrected age. As measured by the three main domains of the Bayley III score: i.e. cognitive score, language composite score and motor composite score. [ Time Frame: at 2 years corrected age ]
   P ≤0.05 will be the level used to indicate statistical significance.Deaths and those infants with severe neurodevelopment disability will be scored 55 in the cognitive domain, 46 in the motor domain and 47 in the language domain. The primary outcome will be ordered as cognitive score, motor composite score and language composite score in all results presented.

Secondary Outcome Measures :

1. Blood levels of T4, TSH and TBG on day 7, 14, 28 and 34 weeks corrected age. [ Time Frame: 2 years corrected age ]
2. Neurodevelopment impairment as a composite of death or a Bayley III score of <85 in any of the score's three main subsets domains: cognitive, language and motor composites. [ Time Frame: 2 years corrected age ]
3. Neurodevelopmental impairment assessed as a difference between the iodine supplemented and placebo groups in each of the four subset scores of the Bayley III i.e. receptive communication, expressive communication, fine motor or gross motor. [ Time Frame: 2 years corrected age ]
4. Type and severity of illness: necrotising enterocolitis [ Time Frame: 2 years corrected age ]
   Type and severity of illness: necrotising enterocolitis
5. Type and severity of illness:persistent ductus arteriosus [ Time Frame: 2 years corrected age ]
   Type and severity of illness:persistent ductus arteriosus
6. Type and severity of illness: respiratory distress [ Time Frame: 2 years corrected age ]
   Type and severity of illness: respiratory distress
7. Type and severity of illness:chronic lung disease (need for oxygen at 36 weeks corrected age) [ Time Frame: 2 years corrected age ]
   Type and severity of illness: chronic lung disease (need for oxygen at 36 weeks corrected age)
8. Cranial ultrasound changes [ Time Frame: 2 years corrected age ]
   cranial ultrasound changes
9. Acquired infection [ Time Frame: 2 years corrected age ]
   Acquired infection as indicated by medical notes during neonatal period
10. Cranial ultrasound changes [ Time Frame: 2 years corrected age ]
    Type and severity of illness: necrotising enterocolitis, persistent ductus arteriosus, respiratory distress , chronic lung disease (need for oxygen at 36 weeks corrected age), cranial ultrasound changes, acquired infection; hearing and vision impairment; postnatal drug use (e.g. diamorphine, dexamethasone, dopamine, caffeine and indomethacin); nutritional status; BAPM level of care; highest recorded bilirubin levels; and death - immediate and underlying causes.
11. Hearing and vision impairment [ Time Frame: 2 years corrected age ]
    Hearing and vision impairment as indicated by parental questionnaire
12. Postnatal drug use [ Time Frame: 2 years corrected age ]
    diamorphine, dexamethasone, dopamine, caffeine and indomethacin
13. Nutritional status [ Time Frame: 2 years corrected age ]
    Nutritional status collected on postnatal day 7, 14, 28 and 34 corrected weeks (as indicated by neonatal drug chart
14. BAPM level of care [ Time Frame: 2 years corrected age ]
    BAPM level of care
15. Highest recorded bilirubin levels [ Time Frame: 2 years corrected age ]
    highest recorded bilirubin levels; and death - immediate and underlying causes.
16. Death - immediate and underlying causes. [ Time Frame: 2 years corrected age ]
    Death - immediate and underlying causes.

Eligibility Criteria

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Ages Eligible for Study:	up to 42 Hours (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• All infants born under 31 weeks gestation

Exclusion Criteria:

• Mother exposed to excess iodine during pregnancy or delivery

Contacts and Locations

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Locations

United Kingdom
Ninewells Hospital and Medical School
Dundee, Tayside, United Kingdom, DD1 9SY
Royal Maternity Hospital
Belfast, United Kingdom, BT12 6BB
Heartlands Hospital
Birmingham, United Kingdom, B9 5SS
University Hospital Coventry
Coventry, United Kingdom, CV2 2DX
Derbyshire Childrens Hospital
Derby, United Kingdom, DE22 3NE
Princess Royal Maternity Hospital
Glasgow, United Kingdom, G31 2ER
Southern General Hospital
Glasgow, United Kingdom, G51 4TF
Crosshouse Hospital
Kilmarnock, United Kingdom, KA2 0BE
Leicester Royal Infirmary
Leicester, United Kingdom, LE1 5WW
Altnagelvin Area Hospital
Londonderry, United Kingdom, BT47 6SB
James Cook University Hospital
Middlesbrough, United Kingdom, TS4 3BW
Royal Victoria Infirmary
Newcastle Upon Tyne, United Kingdom
Nottingham City Hospital
Nottingham, United Kingdom, NG5 1PW
Queen's Medical Centre
Nottingham, United Kingdom, NG7 2UH
Royal Berkshire Hospital
Reading, United Kingdom, RG1 5AN
Jessops Wing Hospital
Sheffield, United Kingdom, S10 2SF
University Hospital of North Tees
Stockton on Tees, United Kingdom
Sunderland City Hospitals
Sunderland, United Kingdom, SR4 7TP
Wishaw General Hospital
Wishaw, United Kingdom, ML2 0DP

Sponsors and Collaborators

University of Oxford

University of Dundee

National Institute for Health Research, United Kingdom

Investigators

Study Director:	Fiona Williams, Dr	University of Dundee
Study Chair:	Peter Brocklehurst, Professor	UCL

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Trial support site 

Publications:

Williams F, Hume R, Ogston S, Brocklehurst P, Morgan K, Juszczak E; I2S2 team. A summary of the iodine supplementation study protocol (I2S2): a UK multicentre randomised controlled trial in preterm infants. Neonatology. 2014;105(4):282-9. doi: 10.1159/000358247. Epub 2014 Feb 27.

Responsible Party:	University of Oxford
ClinicalTrials.gov Identifier:	NCT00638092 History of Changes
Other Study ID Numbers:	08/S0501/31; 2008-001024-31 ( EudraCT Number ); 08/S0501/31 ( Other Identifier: REC Reference ); 09/800/03 ( Other Grant/Funding Number: NIHR EME )
First Posted:	March 18, 2008
Last Update Posted:	May 18, 2015
Last Verified:	May 2015

Keywords provided by University of Oxford:

hypothyroxinemia; preterm infants; iodine	neurodevelopmental outcome; Iodine supplementation; Randomised controlled trial

Additional relevant MeSH terms:

Iodine; Anti-Infective Agents, Local; Anti-Infective Agents; Trace Elements	Micronutrients; Growth Substances; Physiological Effects of Drugs