Clinical trial NCT03066076: Total Thyroidectomy Versus Thionamides in Patients With Moderate-to-Severe Graves' Ophthalmopathy
Official title: Prospective Randomized Clinical Trial of Total Thyroidectomy (Tx) Versus Thionamides (Anti-Thyroid Drugs) in Patients With Moderate-to-Severe Graves' Ophthalmopathy - a 1-year Follow-up
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Graves Disease
Graves Ophthalmopathy
Graves' Ophthalmopathy Worsened
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2017-02-28
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

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

Primary outcomes:
measure: Muscle index (MI) from ultrasound measurements
timeFrame: 12 months
measure: Thyroid antibodies
timeFrame: 12 months
Secondary outcomes:
measure: CAScore/NOSPECS score
timeFrame: 12 months
measure: Superonasal index measurements via ultrasound
timeFrame: 12 months
measure: Quality of life score
timeFrame: 12 months
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Department of Surgery and Department of Ophthalmology Medical University Vienna
Study officials:
affiliation: Medical University Vienna
name: Philipp Riss, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University Vienna
name: Guido Dorner, MD
role: PRINCIPAL_INVESTIGATOR
References: