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

This study has been completed.
Sponsor:
Collaborators:
University of Dundee
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
University of Oxford
ClinicalTrials.gov Identifier:
NCT00638092
First received: March 14, 2008
Last updated: May 15, 2015
Last verified: May 2015
  Purpose

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 Intervention Phase
Transient Hypothyroxinemia
Drug: sodium iodide
Drug: Sodium Chloride
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomised Controlled Trial of Iodide Supplementation in Preterm Infants With Follow-up at 2 Years

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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:
  • Blood levels of T4, TSH and TBG on day 7, 14, 28 and 34 weeks corrected age. [ Time Frame: 2 years corrected age ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Type and severity of illness: necrotising enterocolitis [ Time Frame: 2 years corrected age ] [ Designated as safety issue: No ]
    Type and severity of illness: necrotising enterocolitis

  • Type and severity of illness:persistent ductus arteriosus [ Time Frame: 2 years corrected age ] [ Designated as safety issue: No ]
    Type and severity of illness:persistent ductus arteriosus

  • Type and severity of illness: respiratory distress [ Time Frame: 2 years corrected age ] [ Designated as safety issue: No ]
    Type and severity of illness: respiratory distress

  • Type and severity of illness:chronic lung disease (need for oxygen at 36 weeks corrected age) [ Time Frame: 2 years corrected age ] [ Designated as safety issue: No ]
    Type and severity of illness: chronic lung disease (need for oxygen at 36 weeks corrected age)

  • Cranial ultrasound changes [ Time Frame: 2 years corrected age ] [ Designated as safety issue: No ]
    cranial ultrasound changes

  • Acquired infection [ Time Frame: 2 years corrected age ] [ Designated as safety issue: No ]
    Acquired infection as indicated by medical notes during neonatal period

  • Cranial ultrasound changes [ Time Frame: 2 years corrected age ] [ Designated as safety issue: No ]
    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.

  • Hearing and vision impairment [ Time Frame: 2 years corrected age ] [ Designated as safety issue: No ]
    Hearing and vision impairment as indicated by parental questionnaire

  • Postnatal drug use [ Time Frame: 2 years corrected age ] [ Designated as safety issue: No ]
    diamorphine, dexamethasone, dopamine, caffeine and indomethacin

  • Nutritional status [ Time Frame: 2 years corrected age ] [ Designated as safety issue: No ]
    Nutritional status collected on postnatal day 7, 14, 28 and 34 corrected weeks (as indicated by neonatal drug chart

  • BAPM level of care [ Time Frame: 2 years corrected age ] [ Designated as safety issue: No ]
    BAPM level of care

  • Highest recorded bilirubin levels [ Time Frame: 2 years corrected age ] [ Designated as safety issue: No ]
    highest recorded bilirubin levels; and death - immediate and underlying causes.

  • Death - immediate and underlying causes. [ Time Frame: 2 years corrected age ] [ Designated as safety issue: No ]
    Death - immediate and underlying causes.


Enrollment: 1275
Study Start Date: March 2010
Study Completion Date: May 2015
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Name: sodium iodide
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
Other Name: 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.

  Eligibility

Ages Eligible for Study:   up to 42 Hours
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00638092

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
Southern General Hospital
Glasgow, United Kingdom, G51 4TF
Princess Royal Maternity Hospital
Glasgow, United Kingdom, G31 2ER
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

Additional Information:
Publications:
Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT00638092     History of Changes
Other Study ID Numbers: 08/S0501/31, 2008-001024-31, 08/S0501/31, 09/800/03
Study First Received: March 14, 2008
Last Updated: May 15, 2015
Health Authority: United Kingdom: Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency

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
Anti-Infective Agents, Local
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Trace Elements

ClinicalTrials.gov processed this record on July 01, 2015