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

Transient Hypothyroxinemia Clinical Trial

— I2S2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00638092
• Other study ID #: 08/S0501/31
• Secondary ID: 2008-001024-3108
• Status: Completed
• Phase: Phase 4
• First received: March 14, 2008
• Last updated: May 15, 2015
• Start date: March 2010
• Est. completion date: May 2015

Study information

• Verified date: May 2015
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics CommitteeUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1275
• Est. completion date: May 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 42 Hours

Eligibility

Inclusion Criteria:

• All infants born under 31 weeks gestation

Exclusion Criteria:

• Mother exposed to excess iodine during pregnancy or delivery

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Transient Hypothyroxinemia

Intervention

Drug:
• sodium iodide
sodium iodide 30 micrograms/kg/day, daily dose, from randomisation (within 42 hours of birth) to 34 corrected weeks gestation
• Sodium Chloride
Sodium Chloride 30 micrograms/kg/day, daily dose, from randomisation (from within 42 hours of birth)to 34 corrected weeks gestation

Locations

Country	Name	City	State
United Kingdom	Royal Maternity Hospital	Belfast
United Kingdom	Heartlands Hospital	Birmingham
United Kingdom	University Hospital Coventry	Coventry
United Kingdom	Derbyshire Childrens Hospital	Derby
United Kingdom	Ninewells Hospital and Medical School	Dundee	Tayside
United Kingdom	Princess Royal Maternity Hospital	Glasgow
United Kingdom	Southern General Hospital	Glasgow
United Kingdom	Crosshouse Hospital	Kilmarnock
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	Altnagelvin Area Hospital	Londonderry
United Kingdom	James Cook University Hospital	Middlesbrough
United Kingdom	Royal Victoria Infirmary	Newcastle Upon Tyne
United Kingdom	Nottingham City Hospital	Nottingham
United Kingdom	Queen's Medical Centre	Nottingham
United Kingdom	Royal Berkshire Hospital	Reading
United Kingdom	Jessops Wing Hospital	Sheffield
United Kingdom	University Hospital of North Tees	Stockton on Tees
United Kingdom	Sunderland City Hospitals	Sunderland
United Kingdom	Wishaw General Hospital	Wishaw

Sponsors (3)

Lead Sponsor	Collaborator
University of Oxford	National Institute for Health Research, United Kingdom, University of Dundee

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Blood levels of T4, TSH and TBG on day 7, 14, 28 and 34 weeks corrected age.		2 years corrected age	No
Secondary	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	No
Secondary	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	No
Secondary	Type and severity of illness: necrotising enterocolitis	Type and severity of illness: necrotising enterocolitis	2 years corrected age	No
Secondary	Type and severity of illness:persistent ductus arteriosus	Type and severity of illness:persistent ductus arteriosus	2 years corrected age	No
Secondary	Type and severity of illness: respiratory distress	Type and severity of illness: respiratory distress	2 years corrected age	No
Secondary	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	No
Secondary	Cranial ultrasound changes	cranial ultrasound changes	2 years corrected age	No
Secondary	Acquired infection	Acquired infection as indicated by medical notes during neonatal period	2 years corrected age	No
Secondary	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	No
Secondary	Hearing and vision impairment	Hearing and vision impairment as indicated by parental questionnaire	2 years corrected age	No
Secondary	Postnatal drug use	diamorphine, dexamethasone, dopamine, caffeine and indomethacin	2 years corrected age	No
Secondary	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	No
Secondary	BAPM level of care	BAPM level of care	2 years corrected age	No
Secondary	Highest recorded bilirubin levels	highest recorded bilirubin levels; and death - immediate and underlying causes.	2 years corrected age	No
Secondary	Death - immediate and underlying causes.	Death - immediate and underlying causes.	2 years corrected age	No

External Links

•   Supports programme of work
•   Trial support site