Transient HypothyroxinemiaPhase 4I2S2NCT00638092
A Randomised Controlled Trial of Iodide Supplementation in Preterm Infants Follow-up at 2 Years
A Phase 4 study testing sodium iodide and Sodium Chloride in people with Transient Hypothyroxinemia, run by University of Oxford at 19 sites in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 1 hour to 42 hours
- Conditions the study is for
- Transient Hypothyroxinemia
- What is being tested?
- sodium iodide and Sodium Chloride
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,275 participants
- Where
- 19 sitesUnited Kingdom
- Study dates
- Mar 2010to May 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 hour to 42 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- All infants born under 31 weeks gestation
Who cannot join
- Mother exposed to excess iodine during pregnancy or delivery
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
United Kingdom19 sites
Royal Maternity Hospital
Belfast, BT12 6BB
Heartlands Hospital
Birmingham, B9 5SS
University Hospital Coventry
Coventry, CV2 2DX
Derbyshire Childrens Hospital
Derby, DE22 3NE
Ninewells Hospital and Medical School
Dundee, Tayside, DD1 9SY
Princess Royal Maternity Hospital
Glasgow, G31 2ER
Southern General Hospital
Glasgow, G51 4TF
Crosshouse Hospital
Kilmarnock, KA2 0BE
Leicester Royal Infirmary
Leicester, LE1 5WW
Altnagelvin Area Hospital
Londonderry, BT47 6SB
James Cook University Hospital
Middlesbrough, TS4 3BW
Royal Victoria Infirmary
Newcastle upon Tyne
Nottingham City Hospital
Nottingham, NG5 1PW
Queen's Medical Centre
Nottingham, NG7 2UH
Royal Berkshire Hospital
Reading, RG1 5AN
Jessops Wing Hospital
Sheffield, S10 2SF
University Hospital of North Tees
Stockton-on-Tees
Sunderland City Hospitals
Sunderland, SR4 7TP
Wishaw General Hospital
Wishaw, ML2 0DP
About this study
Official title: 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.
Read the 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.
- Conditions
- Transient Hypothyroxinemia
- Being tested
- sodium iodide, Sodium Chloride
- Keywords
- hypothyroxinemia, preterm infants, iodine, neurodevelopmental outcome, Iodine supplementation, Randomised controlled trial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sodium iodideDrug
sodium iodide 30 micrograms/kg/day, daily dose, from randomisation (within 42 hours of birth) to 34 corrected weeks gestation
Sodium ChlorideDrug
Sodium Chloride 30 micrograms/kg/day, daily dose, from randomisation (from within 42 hours of birth)to 34 corrected weeks gestation
| Study group | Role | What they receive |
|---|---|---|
| Iodine | Experimental | This is the hypothetical active arm Receives: Drug: sodium iodide |
| Placebo | Placebo comparator | this is the hypothetical placebo Receives: Drug: Sodium Chloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: at 2 years corrected age
Secondary outcomes (16)
Blood levels of T4, TSH and TBG on day 7, 14, 28 and 34 weeks corrected age.
Measured: 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.
Measured: 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.
Measured: 2 years corrected age
Type and severity of illness: necrotising enterocolitis
Type and severity of illness: necrotising enterocolitis
Measured: 2 years corrected age
Type and severity of illness:persistent ductus arteriosus
Type and severity of illness:persistent ductus arteriosus
Measured: 2 years corrected age
Type and severity of illness: respiratory distress
Type and severity of illness: respiratory distress
Measured: 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)
Measured: 2 years corrected age
Cranial ultrasound changes
cranial ultrasound changes
Measured: 2 years corrected age
Acquired infection
Acquired infection as indicated by medical notes during neonatal period
Measured: 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.
Measured: 2 years corrected age
Hearing and vision impairment
Hearing and vision impairment as indicated by parental questionnaire
Measured: 2 years corrected age
Postnatal drug use
diamorphine, dexamethasone, dopamine, caffeine and indomethacin
Measured: 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
Measured: 2 years corrected age
BAPM level of care
BAPM level of care
Measured: 2 years corrected age
Highest recorded bilirubin levels
highest recorded bilirubin levels; and death - immediate and underlying causes.
Measured: 2 years corrected age
Death - immediate and underlying causes.
Death - immediate and underlying causes.
Measured: 2 years corrected age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2008 (estimated)
- Study startMar 2010
- Primary completionApr 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Transient HypothyroxinemiaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,275 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- University of Dundee, National Institute for Health Research, United Kingdom
- Responsible party
- Sponsor
- Investigators
- Fiona Williams, Dr, Study director, University of DundeePeter Brocklehurst, Professor, Study chair, UCL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00638092
- Sponsor's protocol ID
- 08/S0501/31
- Other IDs
- 2008-001024-31, 08/S0501/31, 09/800/03, 2008
- Acronym
- I2S2
- Status last verified
- May 2015
- First submitted
- 14 Mar 2008
- Last updated
- 18 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 24576827
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Controlled Trial of Iodide Supplementation in Preterm Infants With Follow-up at 2 Years
- ClinicalTrials.gov ID
- NCT00638092
- Acronym / sponsor ID
- I2S2 / 08/S0501/31
- Conditions
- Transient Hypothyroxinemia
- Keywords
- hypothyroxinemia, preterm infants, iodine, neurodevelopmental outcome, Iodine supplementation, Randomised controlled trial
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,275 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- University of Dundee, National Institute for Health Research, United Kingdom
- Study start
- Mar 2010
- Primary completion
- Apr 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 18 Mar 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Iodine | Experimental | Drug: sodium iodideThis is the hypothetical active arm |
| Placebo | Placebo comparator | Drug: Sodium Chloridethis is the hypothetical placebo |
Who may qualify
- Ages
- 1 hour to 42 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- All infants born under 31 weeks gestation
Key exclusion criteria (1 listed)
- Mother exposed to excess iodine during pregnancy or delivery
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sodium iodidesodium iodide 30 micrograms/kg/day, daily dose, from randomisation (within 42 hours of birth) to 34 corrected weeks gestation | Drug | Iodine |
| Sodium ChlorideSodium Chloride 30 micrograms/kg/day, daily dose, from randomisation (from within 42 hours of birth)to 34 corrected weeks gestation | Drug | Placebo |
Primary outcome
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.
16 secondary outcomes
Blood levels of T4, TSH and TBG on day 7, 14, 28 and 34 weeks corrected age.
Time frame: 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.
Time frame: 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.
Time frame: 2 years corrected age
Type and severity of illness: necrotising enterocolitis
Time frame: 2 years corrected age
Type and severity of illness:persistent ductus arteriosus
Time frame: 2 years corrected age
Type and severity of illness: respiratory distress
Time frame: 2 years corrected age
Type and severity of illness:chronic lung disease (need for oxygen at 36 weeks corrected age)
Time frame: 2 years corrected age
Cranial ultrasound changes
Time frame: 2 years corrected age
Acquired infection
Time frame: 2 years corrected age
Cranial ultrasound changes
Time frame: 2 years corrected age
Hearing and vision impairment
Time frame: 2 years corrected age
Postnatal drug use
Time frame: 2 years corrected age
Nutritional status
Time frame: 2 years corrected age
BAPM level of care
Time frame: 2 years corrected age
Highest recorded bilirubin levels
Time frame: 2 years corrected age
Death - immediate and underlying causes.
Time frame: 2 years corrected age
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2015.
- Background: PubMed 24576827Williams 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.
- Supports programme of workLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fiona Williams, Dr study director
University of Dundee
Peter Brocklehurst, Professor study chair
UCL
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing sodium iodide and Sodium Chloride in people with Transient Hypothyroxinemia, run by University of Oxford at 19 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00638092, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2015.