Observational Study on Hypothyroidism in Young Children Following Iodine Contrast Exposure

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02766283
• Collaborator: (none)
• Enrollment: 843
• Location: 1
• Actual Duration (Months): 2
• Patients Per Site Per Month: 420.6

Study Details

Study Description

Brief Summary

To investigate the incidence of detected hypothyroidism after iodinated contrast exposure in pediatric patients from birth to 3 years of age (inclusive) in a routine clinical practice setting.

Condition or Disease	Intervention/Treatment	Phase
Hypothyroidism	Drug: iodinated contrast agents

Study Design

• Study Type: Observational
• Actual Enrollment: 843 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Observational Study on Hypothyroidism in Young Children Following Iodine Contrast Exposure
• Actual Study Start Date: Jun 30, 2016
• Actual Primary Completion Date: Aug 30, 2016
• Actual Study Completion Date: Aug 30, 2016

Arms and Interventions

Arm	Intervention/Treatment
Iodinated contrast agents children age 0-3 years (inclusive), who underwent a iodine contrast enhanced radiological examination.	Drug: iodinated contrast agents; Intravascular application

Outcome Measures

Primary Outcome Measures

1. Number of Pediatric Patients With Detected Hypothyroidism After Iodinated Contrast Exposure in a Routine Clinical Practice Setting [Up to one year after iodinated contrast material (ICM) exposure (828 person years)]

Secondary Outcome Measures

1. Baseline Characteristics (Sex) of the Cases With Hypothyroidism and of the Rest of the Cohort [Up to one year after ICM exposure (828 person years)]

2. Baseline Characteristics (Age) of the Cases With Hypothyroidism and of the Rest of the Cohort [At first examination]

3. Baseline Characteristics (Weight) of the Cases With Hypothyroidism and of the Rest of the Cohort [Within a range of ±360 days of the first examination]

4. Baseline Characteristics (Comorbidity) of the Cases With Hypothyroidism and of the Rest of the Cohort [Prior to first examination]

5. Baseline Characteristics (Sum of Examinations) in Cases With an Indication of Hypothyroidism and Cases Without [Up to one year after ICM exposure (828 person years)]

6. Baseline Characteristics (Type of 1st Examination) in Cases With an Indication of Hypothyroidism and Cases Without [Up to one year after ICM exposure (828 person years)]

7. Baseline Characteristics (Type of 2nd Examination) in Cases With an Indication of Hypothyroidism and Cases Without [Up to one year after ICM exposure (828 person years)]

8. Baseline Characteristics (Time Between Examinations) in Cases With an Indication of Hypothyroidism and Cases Without [Up to one year after ICM exposure (828 person years)]

9. Time-relation Between Iodine Contrast Exposure and Diagnosis of Hypothyroidism [Up to one year after ICM exposure (828 person years)]

10. The Duration of Hypothyroidism Episode in the "Probable Iodine Induced" Category [Up to one year after ICM exposure (828 person years)]

    Based on the information collected from the database, the probable longest duration of Hypothyroidism was ascertained for the cases below.

11. The Duration of Hypothyroidism Episode in the "Probable Iodine Induced" Category [Up to one year after ICM exposure (828 person years)]

    Based on the information collected from the database, the probable shortest duration of Hypothyroidism was ascertained for the cases below.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 3 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• All children age 0-3 years (inclusive) who are identified of having undergone a radiological examination with intravascular use of an iodinated contrast agent.(e.g.

contrast enhanced CT, cardioangiography)

Exclusion Criteria:

• Congenital Hypothyroidism or other forms of preexisting hypothyroidism

• Preexisting thyroid hormone replacement therapy less than three months of observation before the radiological examination (if greater than three months old)

• Less than two weeks follow-up available after the contrast exposure.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Multiple Locations		Israel

Sponsors and Collaborators

• Bayer

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT02766283
• Other Study ID Numbers: 18614
• First Posted: May 9, 2016
• Last Update Posted: Mar 26, 2018
• Last Verified: Mar 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Bayer: Children; Iodinated contrast agents
• Additional relevant MeSH terms: Hypothyroidism

Study Results

Participant Flow

Recruitment Details	This study was a retrospective cohort study, using the data from the years 1998 until 2015 in the database of Maccabi Health Services (Israel).
Pre-assignment Detail	Between 1.1.1998 and 31.12.2015, 877 participants were identified. After applying exclusion criteria, 34 participants were excluded from the initial cohort and the final cohort consisted of 843 participants.

Arm/Group Title	Iodine Contrast Agent
Arm/Group Description	The data used for this retrospective cohort study was from the years 1998 until 2015. The study population consisted of children ages 0-3 (inclusive) who have undergone a radiological examination with an iodinated contrast agent (contrast enhanced CT and cardio-angiography). Follow-up for the outcome (hypothyroidism) was for up to one year after contrast exposure. Incident cases of hypothyroidism were detected by: thyroid-stimulating hormone (TSH) levels, coded diagnosis of hypothyroidism or start of new thyroid replacement therapy.
Period Title: Overall Study
STARTED	843
COMPLETED	816
NOT COMPLETED	27

Baseline Characteristics

Arm/Group Title	Iodine Contrast Agent
Arm/Group Description	The data used for this retrospective cohort study was from the years 1998 until 2015. The study population consisted of children ages 0-3 (inclusive) who have undergone a radiological examination with an iodinated contrast agent (contrast enhanced CT and cardio-angiography). Follow-up for the outcome (hypothyroidism) was for up to one year after contrast exposure. Incident cases of hypothyroidism were detected by: TSH levels, coded diagnosis of hypothyroidism or start of new thyroid replacement therapy.
Overall Participants	843
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	1.06 (0.87)
Sex: Female, Male (Count of Participants)
Female	382 45.3%
Male	461 54.7%
Weight (Kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilograms]	8.80 (3.39)
Comorbidity (Number) [Number]
Cardio	495 58.7%
Diabetes	1 0.1%
Cancer	21 2.5%
Overweight	12 1.4%
Sum of Examinations (Count of Participants)
1	775 91.9%
>= 2	68 8.1%
Type of 1st examination (Count of Participants)
Cardio-angiography	481 57.1%
CT	362 42.9%
Type of >=2nd examination (Count of Participants)
Cardio-angiography	47 5.6%
CT	21 2.5%
Time between examinations (Days) [Mean (Standard Deviation) ]
First and second	282.79 (252.34)
Second and third	208.19 (180.01)
Third and fourth	212.00 (196.28)
Dispenses of hypothyroidism inducing drugs (Number) [Number]
Anticonvulsants	21 2.5%
Amiodarone	5 0.6%

Outcome Measures

1. Primary Outcome

Title	Number of Pediatric Patients With Detected Hypothyroidism After Iodinated Contrast Exposure in a Routine Clinical Practice Setting
Time Frame	Up to one year after iodinated contrast material (ICM) exposure (828 person years)

Outcome Measure Data

Analysis Population Description

Final Cohort

Arm/Group Title	Iodine Contrast Agent
Arm/Group Description	The data used for this retrospective cohort study was from the years 1998 until 2015. The study population consisted of children ages 0-3 (inclusive) who have undergone a radiological examination with an iodinated contrast agent (contrast enhanced CT and cardio-angiography). Follow-up for the outcome (hypothyroidism) was for up to one year after contrast exposure. Incident cases of hypothyroidism were detected by: TSH levels, coded diagnosis of hypothyroidism or start of new thyroid replacement therapy.
Measure Participants	843
Count of Participants [Participants]	11 1.3%

2. Secondary Outcome

Title	Baseline Characteristics (Sex) of the Cases With Hypothyroidism and of the Rest of the Cohort
Time Frame	Up to one year after ICM exposure (828 person years)

Outcome Measure Data

Analysis Population Description

Final Cohort

Arm/Group Title	No Hypothyroidism Indication	Hypothyroidism Indication
Arm/Group Description	Participants without potential hypothyroidism detected during the one-year follow up period (828 person years)	Participants with potential hypothyroidism detected during the one-year follow up period (828 person years)
Measure Participants	832	11
Male	454 53.9%	7 NaN
Female	378 44.8%	4 NaN

3. Secondary Outcome

Title	Baseline Characteristics (Age) of the Cases With Hypothyroidism and of the Rest of the Cohort
Time Frame	At first examination

Outcome Measure Data

Analysis Population Description

Final Cohort

Arm/Group Title	No Hypothyroidism Indication	Hypothyroidism Indication
Arm/Group Description	Participants without potential hypothyroidism detected during the one-year follow up period (828 person years)	Participants with potential hypothyroidism detected during the one-year follow up period (828 person years)
Measure Participants	832	11
Mean (Standard Deviation) [Years]	1.07 (0.86)	0.53 (0.96)

4. Secondary Outcome

Title	Baseline Characteristics (Weight) of the Cases With Hypothyroidism and of the Rest of the Cohort
Time Frame	Within a range of ±360 days of the first examination

Outcome Measure Data

Analysis Population Description

Final Cohort

Arm/Group Title	No Hypothyroidism Indication	Hypothyroidism Indication
Arm/Group Description	Participants without potential hypothyroidism detected during the one-year follow up period (828 person years)	Participants with potential hypothyroidism detected during the one-year follow up period (828 person years)
Measure Participants	832	11
Mean (Standard Deviation) [Kilograms]	8.84 (3.37)	6.57 (3.74)

5. Secondary Outcome

Title	Baseline Characteristics (Comorbidity) of the Cases With Hypothyroidism and of the Rest of the Cohort
Time Frame	Prior to first examination

Outcome Measure Data

Analysis Population Description

Final Cohort

Arm/Group Title	No Hypothyroidism Indication	Hypothyroidism Indication
Arm/Group Description	Participants without potential hypothyroidism detected during the one-year follow up period (828 person years)	Participants with potential hypothyroidism detected during the one-year follow up period (828 person years)
Measure Participants	832	11
Cardio	485 57.5%	10 NaN
Diabetes	1 0.1%	0 NaN
Cancer	21 2.5%	0 NaN
Overweight	12 1.4%	0 NaN

6. Secondary Outcome

Title	Baseline Characteristics (Sum of Examinations) in Cases With an Indication of Hypothyroidism and Cases Without
Time Frame	Up to one year after ICM exposure (828 person years)

Outcome Measure Data

Analysis Population Description

Final Cohort

Arm/Group Title	No Hypothyroidism Indication	Hypothyroidism Indication
Arm/Group Description	Participants without potential hypothyroidism detected during the one-year follow up period (828 person years)	Participants with potential hypothyroidism detected during the one-year follow up period (828 person years)
Measure Participants	832	11
1	765 90.7%	10 NaN
>=2	67 7.9%	1 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Iodine Contrast Agent, Hypothyroidism Indication
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.90
	Comments
	Method	Chi-squared
	Comments

7. Secondary Outcome

Title	Baseline Characteristics (Type of 1st Examination) in Cases With an Indication of Hypothyroidism and Cases Without
Time Frame	Up to one year after ICM exposure (828 person years)

Outcome Measure Data

Analysis Population Description

Final Cohort

Arm/Group Title	No Hypothyroidism Indication	Hypothyroidism Indication
Arm/Group Description	Participants without potential hypothyroidism detected during the one-year follow up period (828 person years)	Participants with potential hypothyroidism detected during the one-year follow up period (828 person years)
Measure Participants	832	11
Cardio-angiography	471 55.9%	10 NaN
CT	361 42.8%	1 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Iodine Contrast Agent, Hypothyroidism Indication
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.022
	Comments
	Method	Chi-squared
	Comments

8. Secondary Outcome

Title	Baseline Characteristics (Type of 2nd Examination) in Cases With an Indication of Hypothyroidism and Cases Without
Time Frame	Up to one year after ICM exposure (828 person years)

Outcome Measure Data

Analysis Population Description

Final Cohort

Arm/Group Title	No Hypothyroidism Indication	Hypothyroidism Indication
Arm/Group Description	Participants without potential hypothyroidism detected during the one-year follow up period (828 person years)	Participants with potential hypothyroidism detected during the one-year follow up period (828 person years)
Measure Participants	832	11
Cardio-angiography	46 5.5%	1 NaN
CT	21 2.5%	0 NaN

9. Secondary Outcome

Title	Baseline Characteristics (Time Between Examinations) in Cases With an Indication of Hypothyroidism and Cases Without
Time Frame	Up to one year after ICM exposure (828 person years)

Outcome Measure Data

Analysis Population Description

Final Cohort

Arm/Group Title	No Hypothyroidism Indication	Hypothyroidism Indication
Arm/Group Description	Participants without potential hypothyroidism detected during the one-year follow up period (828 person years)	Participants with potential hypothyroidism detected during the one-year follow up period (828 person years)
Measure Participants	832	11
First and second	282.72 (254.24)	288 (NA)
Second and third	208.19 (180.01)
Third and fourth	212.00 (196.28)

10. Secondary Outcome

Title	Time-relation Between Iodine Contrast Exposure and Diagnosis of Hypothyroidism
Time Frame	Up to one year after ICM exposure (828 person years)

Outcome Measure Data

Analysis Population Description

Final Cohort

Arm/Group Title	Final Cohort
Arm/Group Description	Participants without potential hypothyroidism detected during the one-year follow up period (828 person years)
Measure Participants	828
Mean (Standard Deviation) [Days]	76.54 (93.05)

11. Secondary Outcome

Title	The Duration of Hypothyroidism Episode in the "Probable Iodine Induced" Category
Description	Based on the information collected from the database, the probable longest duration of Hypothyroidism was ascertained for the cases below.
Time Frame	Up to one year after ICM exposure (828 person years)

Outcome Measure Data

Analysis Population Description

Probable iodine-induced hypothyroidism: (N=8) included all potential cases of hypothyroidism with no other cause than the previous ICM exposure could be identified.

Arm/Group Title	Probable Iodine-induced Hypothyroidism
Arm/Group Description	Included all potential cases of hypothyroidism with no other cause than the previous ICM exposure could be identified.
Measure Participants	8
Case number 2	NA
Case number 3	2
Case number 6	NA
Case number 10	2

12. Secondary Outcome

Title	The Duration of Hypothyroidism Episode in the "Probable Iodine Induced" Category
Description	Based on the information collected from the database, the probable shortest duration of Hypothyroidism was ascertained for the cases below.
Time Frame	Up to one year after ICM exposure (828 person years)

Outcome Measure Data

Analysis Population Description

Probable iodine-induced hypothyroidism: (N=8) included all potential cases of hypothyroidism with no other cause than the previous ICM exposure could be identified.

Arm/Group Title	Probable Iodine-induced Hypothyroidism
Arm/Group Description	Included all potential cases of hypothyroidism with no other cause than the previous ICM exposure could be identified.
Measure Participants	8
Case number 4	4
Case number 7	10

13. Secondary Outcome

Title	The Duration of Hypothyroidism Episode in the "Probable Iodine Induced" Category
Description	Based on the information collected from the database, the probable shortest duration of Hypothyroidism was ascertained for the cases below.
Time Frame	Up to one year after ICM exposure (828 person years)

Outcome Measure Data

Analysis Population Description

Probable iodine-induced hypothyroidism: (N=8) included all potential cases of hypothyroidism with no other cause than the previous ICM exposure could be identified.

Arm/Group Title	Probable Iodine-induced Hypothyroidism
Arm/Group Description	Included all potential cases of hypothyroidism with no other cause than the previous ICM exposure could be identified.
Measure Participants	8
Case number 5	14
Case number 11	8

Adverse Events

Time Frame	Up to one year after contrast exposure.
Adverse Event Reporting Description	This study is a retrospective study using data from the database in Israel. The safety outcome focused on the incidence of hypothyroidism for up to one year after iodine contrast exposure, detected by: TSH levels, coded diagnosis of hypothyroidism or start of new thyroid replacement therapy. Please refer to the result of primary outcome measure.
Arm/Group Title	Iodine Contrast Agent
Arm/Group Description	The data used for this retrospective cohort study was from the years 1998 until 2015. The study population consisted of children ages 0-3 (inclusive) who have undergone a radiological examination with an iodinated contrast agent (contrast enhanced CT and cardio-angiography). Follow-up for the outcome (hypothyroidism) was for up to one year after contrast exposure. Incident cases of hypothyroidism were detected by: TSH levels, coded diagnosis of hypothyroidism or start of new thyroid replacement therapy.
All Cause Mortality
	Iodine Contrast Agent
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Iodine Contrast Agent
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Iodine Contrast Agent
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

This study is a retrospective database analysis study. The safety outcome focused on the incidence of hypothyroidism for up to one year after iodine contrast exposure. Please refer to the result of primary outcome measure for safety evaluation.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.