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Trial registered on ANZCTR


Registration number
ACTRN12614000560695
Ethics application status
Approved
Date submitted
20/03/2014
Date registered
26/05/2014
Date last updated
26/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Does the use of an iodine-containing contrast agent to visualise the PICC tip in preterm babies cause hypothyroidism? A randomised controlled trial
Scientific title
Does the use of an iodine-containing contrast agent to visualise the PICC tip in preterm babies cause hypothyroidism? A randomised controlled trial
Secondary ID [1] 284272 0
NIL
Universal Trial Number (UTN)
U1111-1154-5686
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypothyroidism
 291403 0
premature birth 291996 0
Condition category
Condition code
Metabolic and Endocrine 291764 291764 0 0
Thyroid disease
Reproductive Health and Childbirth 292344 292344 0 0
Complications of newborn

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure

Venous or arterial blood samples 0.5ml to be collected for free Thyroxine( FT4) and Thyroid stimulating hormone( TSH) anytime after 48 hours of life before inserting longline both from case and control.
Urine 1-5ml to be collected for iodine/iodine-creatinine ratio anytime after 48 hours of life before inserting longline .
Longline is inserted and 0.3ml of contrast iopamidol containing iodine 300mg/ml (ISOVUE 300) taken in a 5ml syringe is injected after the Xray technician comes just before shooting in case only.
Urine 1-5ml for iodine should be collected between 1-8 hours after injecting contrast .
Repeat FT4 and TSH 7, 14days after insertion of line. (21,28,42 and 60 days thyroid function tests( TFTs) are done if day 7 or 14 test result is abnormal.)
Intervention code [1] 288981 0
Other interventions
Comparator / control treatment

Venous or arterial blood samples 0.5ml to be collected for FT4 and TSH anytime after 48 hours of life before inserting longline both from case and control.
Urine 1-5ml to be collected for iodine/iodine-creatinine ratio anytime after 48 hours of life before inserting longline .
Longline is inserted and 0.3ml of saline taken in a 5ml syringe is injected .
Urine 1-5ml for iodine should be collected between 1-8 hours after injecting saline.
Repeat FT4 and TSH for both case and control 7, 14days after insertion of line.
Control group
Placebo

Outcomes
Primary outcome [1] 291693 0
Clinical Hypothyroidism (FT4- < 10pmol/L for any age
TSH- > 12mIU/L for any age)
Timepoint [1] 291693 0
7 and 14 days after injecting contrast
Secondary outcome [1] 307303 0
Longline tip position identification independently by 2 doctors
Timepoint [1] 307303 0
Immediately after injecting contrast and xray
Secondary outcome [2] 307304 0
Length of impact of iodine on hypothyroidism by doing repeat TFTs on day 21,28,42 and 60.
Timepoint [2] 307304 0
Maximum 2 months(21,28,42 and 60 days thyroid function tests are done if day 7 or 14 test is abnormal)

Eligibility
Key inclusion criteria
Preterms < 30 weeks requiring PICC line after 48 hours of life
Minimum age
48 Hours
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Maternal hypothyroidism/hyperthyroidism
Maternal use of povidone iodine during delivery
Maternal intake of >1100microgram/day Iodine in food or supplements
Maternal intake of antithyroid drugs, Amiodarone
Syndromic babies
Babies on dopamine, steroids, Amiodarone
SGA(small for gestational age) babies(<3rd centile)
Initial abnormal thyroid function test
Neonates having topical povidone iodine exposure
Babies requiring multiple long lines with the previous exposure to contrast

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Covariate adaptive randomization- Covariates like gestational age, sex shall be taken in to consideration
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety
Statistical methods / analysis
1. Diagrammatic representation.
2. Student t test
3. Chi squared test

Rough population size at our hospital per year requiring long line-50
Confidence level-95%
Proportion- 16% From previous studies 1,2,3,4,5,6,7,8)
Confidence interval-0.05
Standard error- 0.01531
Sample size- case41 and control 41
However we will start it as a pilot study with 20 control and 20 case group.
1. Ares S, Pastor I, Quero J, Morreale dE. Thyroid complications, including overt hypothyroidism, related to the use of non-radiopaque silastic catheters for parenteral feeding in prematures requiring injection of small amounts of an iodinated contrast medium. Acta Paediatr 1995; 84: 579–81.
2. Parravicini E, Fontana C, Paterlini GL, Tagliabue P, Rovelli F, Leung K, et al. Iodine, thyroid function, and very low birth weight infants. Pediatrics 1996; 98(4 Pt 1): 730–4.
3. Bona G, Zaffaroni M, Defilippi C, Gallina MR, Mostert M. Effects of iopamidol on neonatal thyroid function. Eur J Radiol 1992; 14: 22–5.
4. l’Allemand D, Gruters A, Beyer P, Weber B. Iodine in contrast agents and skin disinfectants is the major cause for hypothyroidism in premature infants during intensive care. Horm Res 1987; 28: 42–9.
5. Dembinski J, Arpe V, Kroll M, Hieronimi G, Bartmann P. Thyroid function in very low birthweight infants after intravenous administration of the iodinated contrast medium iopromide. Arch Dis Child Fetal Neonatal Ed 2000; 82: F215–7.
6. Giroux JD, Sizun J, Rubio S, Metz C, Montaud N, Guillois B, et al. Transient hypothyroidism after iodine opacification of epicutaneo-caval catheters in neonatal intensive care. Arch Fr Pediatr 1993; 50: 273.
7. Linder N, Sela B, German B, Davidovitch N, Kuint J, Hegesh J, et al. Iodine and hypothyroidism in neonates with congenital heart disease. Arch Dis Child Fetal Neonatal Ed 1997; 77: F239–40.
8. Saule H, Preissler E, Frasch W, Adams G. Iodine burden in premature infants in roentgenologically controlled positioning of central venous silastic catheters. [German]. Monatsschr Kinderheilkd 1986; 134: 21–4.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/07/2014
Actual
4/11/2014
Date of last participant enrolment
Anticipated
30/06/2015
Actual
2/12/2016
Date of last data collection
Anticipated
Actual
19/12/2016
Sample size
Target
41
Accrual to date
Final
41
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 2192 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 7869 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 288894 0
Hospital
Name [1] 288894 0
royal north shore hospital
Country [1] 288894 0
Australia
Primary sponsor type
Hospital
Name
Royal North Shore Hospital
Address
Royal North Shore Hospital
reserve road
st leonards
nsw 2065
Country
Australia
Secondary sponsor category [1] 287591 0
None
Name [1] 287591 0
none
Address [1] 287591 0
none
Country [1] 287591 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290727 0
Northern sydney coast Human Research Ethics Committee (EC00112)
Ethics committee address [1] 290727 0
Kolling Institute of Medical Research,
Research Office, Level 13
Royal North Shore Hospital
St Leonards NSW 2065
Ethics committee country [1] 290727 0
Australia
Date submitted for ethics approval [1] 290727 0
10/04/2014
Approval date [1] 290727 0
06/08/2014
Ethics approval number [1] 290727 0
RESP/14/128

Summary
Brief summary
Preterm babies take time to reach their full quota of oral feeds so often require prolonged intravenous nutrition. Peripheral venous cannulas have a short life span and may result in damage to the skin’s integrity, as well as having a short life span. Long lines or peripherally inserted central catheters(PICC) have a significantly longer life span as the tip is positioned in a large vein.However PICC line insertions are not without complications. The tip of the catheter may reach deep inside the cardiac chambers or fall short of the caval veins and end in entirely unexpected locations. Extravasation of fluid from the catheters in each of these positions has led to serious, and occasionally lethal, complications. These can be avoided if the catheter tip can be precisely localised. The narrow calibre silastic line cannot always be seen on plain radiography but can be visualised with use of a small amount of radio-opaquae contrast.
However the contrast available contains Iodine which may cause transient hypothyroidism in newborns. Concerns regarding this have resulted in some units including ours restricting use of contrast when determining line position. The data supporting this decision are very limited and it is unclear as to the role of iodine containing contrast in the development of hypothyroidism. The few studies that have assessed the relationship are either cohort studies, before-and-after study or case series, none being a randomized control trial. The results of these studies are contrasting without any clear answer as to whether perceived benefits of withholding contrast outweigh the risks of developing hypothyroidism. To confuse things further, asymptomatic hypothyroidism is not uncommon in the preterm population.
The aim of our study is to compare thyroid function tests in preterm neonates after exposure to IV contrast with controls, to ascertain the impact of a small iodine exposure on the thyroid gland in relation to gestational age. The study will be a randomized control trial for babies less than 30 weeks old requiring insertion of a PICC line. Study infants will be randomised to use of contrast(0.3ml Iopamidol containing iodine 300mg/ml)to assess line position(previous Unit practice) or no contrast. Blood and urine tests will be performed to assess any impact on the thyroid gland of contrast use. Repeat thyroid function tests(TFT) for both case and control will be taken as baseline then 7 and 14days after insertion of the line. Further TFT will be taken if day 7 or 14 results are abnormal.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 46982 0
A/Prof Martin Kluckow
Address 46982 0
Department of Neonatology
Level 5, Douglas building
Royal North Shore Hospital
Pacific Highway
st Leonards
nsw 2065
Country 46982 0
Australia
Phone 46982 0
+61 2 94632180
Fax 46982 0
Email 46982 0
[email protected]
Contact person for public queries
Name 46983 0
Martin Kluckow
Address 46983 0
Department of Neonatology
Level 5, Douglas building
Royal North Shore Hospital
Pacific Highway
st Leonards
nsw 2065
Country 46983 0
Australia
Phone 46983 0
+61 2 94632180
Fax 46983 0
Email 46983 0
[email protected]
Contact person for scientific queries
Name 46984 0
Martin Kluckow
Address 46984 0
Department of Neonatology
Level 5, Douglas building
Royal North Shore Hospital
Pacific Highway
st Leonards
nsw 2065
Country 46984 0
Australia
Phone 46984 0
+61 2 94632180
Fax 46984 0
Email 46984 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseDoes the use of an iodine-containing contrast agent to visualise the PICC tip in preterm babies cause hypothyroidism? A randomised controlled trial.2019https://dx.doi.org/10.1136/archdischild-2017-314665
N.B. These documents automatically identified may not have been verified by the study sponsor.