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

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

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.

Study Overview

• Status: Completed
• Conditions: Transient Hypothyroxinemia
• Intervention / Treatment: Drug: sodium iodide; Drug: Sodium Chloride

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 Type: Interventional
• Enrollment (Actual): 1275
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 hour to 1 day (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All infants born under 31 weeks gestation

Exclusion Criteria:

• Mother exposed to excess iodine during pregnancy or delivery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	at 2 years corrected age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood levels of T4, TSH and TBG on day 7, 14, 28 and 34 weeks corrected age.		2 years corrected age
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.		2 years corrected age
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.		2 years corrected age
Type and severity of illness: necrotising enterocolitis	Type and severity of illness: necrotising enterocolitis	2 years corrected age
Type and severity of illness:persistent ductus arteriosus	Type and severity of illness:persistent ductus arteriosus	2 years corrected age
Type and severity of illness: respiratory distress	Type and severity of illness: respiratory distress	2 years corrected age
Type and severity of illness:chronic lung disease (need for oxygen at 36 weeks corrected age)	Type and severity of illness: chronic lung disease (need for oxygen at 36 weeks corrected age)	2 years corrected age
Cranial ultrasound changes	cranial ultrasound changes	2 years corrected age
Acquired infection	Acquired infection as indicated by medical notes during neonatal period	2 years corrected age
Cranial ultrasound changes	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.	2 years corrected age
Hearing and vision impairment	Hearing and vision impairment as indicated by parental questionnaire	2 years corrected age
Postnatal drug use	diamorphine, dexamethasone, dopamine, caffeine and indomethacin	2 years corrected age
Nutritional status	Nutritional status collected on postnatal day 7, 14, 28 and 34 corrected weeks (as indicated by neonatal drug chart	2 years corrected age
BAPM level of care	BAPM level of care	2 years corrected age
Highest recorded bilirubin levels	highest recorded bilirubin levels; and death - immediate and underlying causes.	2 years corrected age
Death - immediate and underlying causes.	Death - immediate and underlying causes.	2 years corrected age

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: National Institute for Health Research, United Kingdom; University of Dundee
• Investigators: Study Director: Fiona Williams, Dr, University of Dundee; Study Chair: Peter Brocklehurst, Professor, UCL

Publications and helpful links

General 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.

Helpful Links

• Supports programme of work

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: March 14, 2008
• First Submitted That Met QC Criteria: March 14, 2008
• First Posted (Estimate): March 18, 2008

Study Record Updates

• Last Update Posted (Estimate): May 18, 2015
• Last Update Submitted That Met QC Criteria: May 15, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Randomised controlled trial; preterm infants; iodine; neurodevelopmental outcome; hypothyroxinemia; Iodine supplementation
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: 08/S0501/31 (Other Identifier: REC Reference); 2008-001024-31 (EudraCT Number); 09/800/03 (Other Grant/Funding Number: NIHR EME)