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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]

NIL

Universal Trial Number (UTN)

U1111-1154-5686

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Hypothyroidism

premature birth

Condition category

Condition code

Metabolic and Endocrine

Thyroid disease

Reproductive Health and Childbirth

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]

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]

Clinical Hypothyroidism (FT4- < 10pmol/L for any age
TSH- > 12mIU/L for any age)

Timepoint [1]

7 and 14 days after injecting contrast

Secondary outcome [1]

Longline tip position identification independently by 2 doctors

Timepoint [1]

Immediately after injecting contrast and xray

Secondary outcome [2]

Length of impact of iodine on hypothyroidism by doing repeat TFTs on day 21,28,42 and 60.

Timepoint [2]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Royal North Shore Hospital - St Leonards

Recruitment postcode(s) [1]

2065 - St Leonards

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

royal north shore hospital

Address [1]

reserve road
st leonards
nsw 2065

Country [1]

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]

None

Name [1]

none

Address [1]

none

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Northern sydney coast Human Research Ethics Committee (EC00112)

Ethics committee address [1]

Kolling Institute of Medical Research,
Research Office, Level 13
Royal North Shore Hospital
St Leonards NSW 2065

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

10/04/2014

Approval date [1]

06/08/2014

Ethics approval number [1]

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

A/Prof Martin Kluckow

Address

Department of Neonatology
Level 5, Douglas building
Royal North Shore Hospital
Pacific Highway
st Leonards
nsw 2065

Country

Australia

Phone

+61 2 94632180

Fax

[email protected]

Contact person for public queries

Name

Martin Kluckow

Address

Department of Neonatology
Level 5, Douglas building
Royal North Shore Hospital
Pacific Highway
st Leonards
nsw 2065

Country

Australia

Phone

+61 2 94632180

Fax

[email protected]

Contact person for scientific queries

Name

Martin Kluckow

Address

Department of Neonatology
Level 5, Douglas building
Royal North Shore Hospital
Pacific Highway
st Leonards
nsw 2065

Country

Australia

Phone

+61 2 94632180

Fax

[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

Source	Title	Year of Publication	DOI
Embase	Does the use of an iodine-containing contrast agent to visualise the PICC tip in preterm babies cause hypothyroidism? A randomised controlled trial.	2019	https://dx.doi.org/10.1136/archdischild-2017-314665

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically