Total Thyroidectomy Versus Thionamides in Patients With Moderate-to-Severe Graves' Ophthalmopathy

Phase 3

• Conditions: Graves Disease; Graves' Ophthalmopathy Worsened; Graves Ophthalmopathy
• Interventions: Drug: Antithyroid Drug; Procedure: Total thyroidectomy

• Registration Number: NCT03066076
• Lead Sponsor: Medical University of Vienna

Brief Summary

Introduction: Graves disease (GD) is characterized by thyrotoxicosis and goiter, arising through circulating autoantibodies that bind to and stimulate the thyroid hormone receptor (TSHR). Graves' ophthalmopathy (GO) is characterized by inflammation, expansion of the extraocular muscles and an increase in retroorbital fat. There are currently three forms of therapies offered: anti-thyroid drugs (ATD) (thionamides), radioactive iodine (RAI) and total thyroidectomy (Tx). There is currently no consensus on the treatment of Grave's disease and GO.

Objective: To examine the difference in the outcome of GO in patients with moderate-to-severe GO, who receive Tx versus further ATD after suffering their first relapse of GO or in which GO stays the same following the initial decrease in ATD therapy after 6 months.

Methods: This prospective randomized clinical trial with observer blinded analysis will analyze 60 patients with moderate-to-severe GO who receive Tx versus ATD without surgery. Main outcome variables include: muscle index measurements via ultrasound and thyroid antibody levels. Additional outcome variables include: CAScore/NOSPECS score, superonasal index measurements via ultrasound and quality of life score.

Detailed Description

Introduction: Graves disease (GD) is characterized by thyrotoxicosis and goiter, arising through circulating autoantibodies that bind to and stimulate the thyroid hormone receptor (TSHR). Graves' ophthalmopathy (GO) is characterized by inflammation, expansion of the extraocular muscles and an increase in retroorbital fat. There are currently three forms of therapies offered: anti-thyroid drugs (ATD) (thionamides), radioactive iodine (RAI) and total thyroidectomy (Tx). There is currently no consensus on the treatment of Grave's disease and GO.

Objective: To examine the difference in the outcome of GO in patients with moderate-to-severe GO, who receive Tx versus further ATD after suffering their first relapse of GO or in which GO stays the same following the initial decrease in ATD therapy after 6 months.

Methods: This prospective randomized clinical trial with observer blinded analysis will analyze 60 patients with moderate-to-severe GO who receive Tx versus ATD without surgery. Main outcome variables include: muscle index measurements via ultrasound and thyroid antibody levels. Additional outcome variables include: CAScore/NOSPECS score, superonasal index measurements via ultrasound and quality of life score.

Study Timeline

• Study First Submitted: 2017-01-27
• Status Verified: 2017-02
• Study First Submitted QC: 2017-02-22
• Last Update Submitted: 2017-02-22
• Study First Posted: 2017-02-28
• Last Update Posted: 2017-02-28
• Study Start: 2017-03-01
• Primary Completion: 2019-02-01
• Study Completion: 2019-06-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. GD and GO onset < 12 months
2. no previous GD treatment other than antithyroid drugs (ATD)
3. first relapse after decrease of antithyroid medication within 4-6 months
4. GO treatment with glucocorticoids based on the Kahaly scheme
5. patients under ATD with normal thyroid function or subclinical hyperthyroid function and moderate-to-severe GO
6. clinically active inflammation according to CAScore (>3/7)
7. informed consent

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Exclusion Criteria

1. GD and GO onset > 12 months
2. more than one relapse of GO longer than 6 months from diagnosis
3. previous GD treatment by RAI or surgery
4. SNI greater than 7.0
5. urgent orbital decompression surgery
6. loss of vision
7. loss of visual field
8. loss of color vision
9. patients not receiving glucocorticoids for GO
10. cytological findings of postsurgical histopathological results suspicious for malignancy
11. pregnancy or breast-feeding
12. contraindication to GC
13. halt of GC therapy
14. Patients with diabetes mellitus
15. age below 18 years
16. no informed consent

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Thyroidectomy	Antithyroid Drug	Total thyroidectomy
Antithyroid drug	Total thyroidectomy	Thiamazol, Propylthiouracil

Primary Outcome Measures

Name	Time	Method
Muscle index (MI) from ultrasound measurements	12 months	Muscle index (MI) from ultrasound measurements
Thyroid antibodies	12 months	Thyroid antibodies

Secondary Outcome Measures

Name	Time	Method
CAScore/NOSPECS score	12 months	CAScore/NOSPECS score
Quality of life score	12 months	Quality of life score
Superonasal index measurements via ultrasound	12 months	Superonasal index measurements via ultrasound

Trial Locations

Locations (1)

Department of Surgery and Department of Ophthalmology Medical University Vienna; 🇦🇹 Vienna, Austria