Graves' OrbitopathyPhase 3ABLAGONCT04776993
A Conservative vs an Ablative Approach for Treatment of Hyperthyroidism in Patients With Graves' Orbitopathy
A Phase 3 study testing Methimazole and Radioiodine or thyroidectomy in people with Graves' Orbitopathy, run by University of Pisa at 1 site in Italy.
Trial summary
Graves' disease (GD) is the most frequent cause of hyperthyroidism in iodine sufficient countries and Graves' orbitopathy (GO) is its most common extrathyroidal manifestation. Restoration and maintenance of euthyroidism are imperative in Graves' disease patients with GO. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Graves' Orbitopathy
- What is being tested?
- Methimazole and Radioiodine or thyroidectomy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteItaly
- Study dates
- 2 Mar 2023to 1 Mar 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients willing and capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
- A diagnosis of Graves' disease based on the presence of hyperthyroidism associated with detectable anti-thyrotropic hormone (TSH) receptor autoantibodies (TRAb). Patients must be euthyroid under control on stable medical regimen and every effort will be made to maintain the euthyroid status for the entire duration of the clinical trial.
- Duration of Graves' disease shorter than 18 months
- A moderate-to-severe GO, defined as the presence of at least one of the following criteria in the most affected eye: an exophthalmos ≥2 mm compared with normal values for sex and race; presence of inconstant to constant diplopia; a lid retraction ≥2 mm
- Active GO: CAS ≥ 3 out of 7 points in the most affected eye. Taking into account severity (moderate-to-severe) and activity (CAS ≥ 3/7) of GO, patients are eligible for methylprednisolone treatment according to clinical practice.
- Duration of GO shorter than 18 months
- Male and female patients of age 18-75 years
- Compliant patient, regular follow-up possible
Who cannot join
- Optic neuropathy
- Previous therapy for Graves' disease with radioiodine or thyroidectomy
- Corticosteroids or other immunosuppressive treatment for GO or other reasons in the last 3 months.
- Previous surgical treatment and/or radiotherapy for GO
- Contraindications to GC: hypersensitivity to the active substance or to any of the excipients; uncontrolled hypertension, uncontrolled diabetes; history of peptic ulcer; urinary infections, glaucoma, systemic fungal infections, systemic infections unless appropriate therapy is employed, idiopathic thrombocytopenic purpura, cerebral edema associated with malaria.
- Use of medications interfering with GC or increasing the risk of GC-related adverse events (see prohibited therapies)
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- Acute or chronic liver disease
- Contraindications to ATD: hypersensitivity to the active substance or to any of the excipients; breastfeeding
- Women of childbearing potential (WOCBP, namely not in menopause or in menopause since less than two years; in all other instances women will be considered as non-WOCBP) and men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year (as indicated in Appendix) for at least 6 and 7,5 months, respectively, after the last dose of the investigational drug (see also 2014_09_HMA_CTFG_Contraception.pdf, namely the "2014 CTFG Reccommendtions related to contraception and pregnancy testing in clinical trials")
- Contraindications of any kind to perform thyroidectomy
- Mental illness that prevent patients from comprehensive, written informed consent
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Endocrinology Unit II
Pisa, PI, 56124
Michele Marinò, MD, +39050997346, michele.marino@med.unipi.it
Giulia Lanzolla, MD, +39050997346, giulia.lanzolla8@gmail.com
About this study
Official title: A Phase III, Randomized, Controlled, Open Label, no Profit, Single-center Intervention Study to Compare the Effect of a Conservative (Antithyroid Drugs) and an Ablative Approach (Radioiodine or Total Thyroidectomy) for the Treatment of Hyperthyroidism in Patients With Graves' Disease and Moderate-to-severe and Active Graves' Orbitopathy (GO) Treated With Intravenous Glucocorticoids (ABLAGO Study)
Graves' disease (GD) is the most frequent cause of hyperthyroidism in iodine sufficient countries and Graves' orbitopathy (GO) is its most common extrathyroidal manifestation. Restoration and maintenance of euthyroidism are imperative in Graves' disease patients with GO. The main treatment options for Graves' hyperthyroidism are antithyroid drugs, radioactive iodine (RAI), and surgery. Whether one or the other therapy for Graves' hyperthyroidism offers the best protection against GO is not established. The study is aimed at comparing the effects of a conservative approach (antithyroid drugs, ATDs, experimental arm) vs an ablative approach (radioiodine or total thyroidectomy) of thyroid treatment on the overall outcome of GO in patients with GD and moderate-to-severe and active GO treated with intravenous glucocorticoids.
- Conditions
- Graves' Orbitopathy
- Being tested
- Methimazole, Radioiodine or thyroidectomy
- Medical subject headings
- Graves Ophthalmopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethimazoleDrug
Also called MMI
Methimazole for 72 weeks
Radioiodine or thyroidectomyProcedure or surgery
Also called Thyroid ablation
Treatment with radioiodine or with thyroidectomy
| Study group | Role | What they receive |
|---|---|---|
| Methimazole | Experimental | Antithyroid drugs (at individualized dosage) for 72 weeks and a cumulative dose of 4.5 g of methylprednisolone divided into 12 weekly infusions Receives: Drug: Methimazole |
| Thyroid ablation | Active comparator | Radioiodine therapy or total thyroidectomy (according to ultrasound thyroid volume) and a cumulative dose of 4.5 g of methylprednisolone divided into 12 weekly infusions Receives: Procedure: Radioiodine or thyroidectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall GO outcome
Improvement is defined as change in two of the following outcome measures in at least one eye, without deterioration in any of the same measures in both eyes (compared to baseline):
- Improvement in CAS by at least 2 points
- Improvement in exophthalmos by at least 2 mm (Hertel exophthalmometer)
- Improvement in lid aperture by at least 2 mm
- Improvement in diplopia (disappearance or change in the degree)
- Improvement of visual acuity by at least 0.2/1
Patients meeting the improvement criteria will be considered as "responders". All other patients will be considered as "non-responders".
Measured: 24 weeks
Secondary outcomes (4)
Overall GO outcome
Improvement is defined as change in two of the following outcome measures in at least one eye, without deterioration in any of the same measures in both eyes (compared to baseline):
- Improvement in CAS by at least 2 points
- Improvement in exophthalmos by at least 2 mm (Hertel exophthalmometer)
- Improvement in lid aperture by at least 2 mm
- Improvement in diplopia (disappearance or change in the degree)
- Improvement of visual acuity by at least 0.2/1
Patients meeting the improvement criteria will be considered as "responders". All other patients will be considered as "non-responders".
Measured: 48 weeks
Overall GO outcome
Improvement is defined as change in two of the following outcome measures in at least one eye, without deterioration in any of the same measures in both eyes (compared to baseline):
- Improvement in CAS by at least 2 points
- Improvement in exophthalmos by at least 2 mm (Hertel exophthalmometer)
- Improvement in lid aperture by at least 2 mm
- Improvement in diplopia (disappearance or change in the degree)
- Improvement of visual acuity by at least 0.2/1
Patients meeting the improvement criteria will be considered as "responders". All other patients will be considered as "non-responders".
Measured: 72 weeks
Response of individual GO parameters: proptosis, CAS, eyelid width, diplopia, and visual acuity
Improvement is defined as change in each of the following outcome measures in at least one eye, without deterioration in both eyes (compared to baseline):
- Improvement in CAS by at least 2 points
- Improvement in exophthalmos by at least 2 mm (Hertel exophthalmometer)
- Improvement in lid aperture by at least 2 mm
- Improvement in diplopia (disappearance or change in the degree)
- Improvement of visual acuity by at least 0.2/1
Patients meeting the improvement criteria will be considered as "responders". All other patients will be considered as "non-responders".
Measured: 24, 48 and 72 weeks
Quality of life questionnaire
Comparison of a disease specific quality of life questionnaire (GO-QoL) at 24, 48 and 72 weeks. Positive response: an improvement in the questionnaire by at least 6/48 points. The GO-QoL contains 8 questions on visual functioning and 8 questions on appearance. The minimal clinically important difference in scores is ≥ 10 points for invasive therapies, but a change of 6 is already perceived by patients as beneficial and is associated with an important change in daily functioning. The GO-QoL is well validated, widely used, and available in eight languages. The GO-QoL is recommended as an independent outcome measure in randomized clinical trials24.
Measured: 24, 48 and 72 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2021
- Study start2 Mar 2023
- Primary completion1 Sep 2024 (estimated)
- Study completion1 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graves' OrbitopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pisa
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marinò Michele, University of Pisa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04776993
- Sponsor's protocol ID
- ABLAGO
- Acronym
- ABLAGO
- Status last verified
- Mar 2023
- First submitted
- 25 Feb 2021
- Last updated
- 17 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomized, Controlled, Open Label, no Profit, Single-center Intervention Study to Compare the Effect of a Conservative (Antithyroid Drugs) and an Ablative Approach (Radioiodine or Total Thyroidectomy) for the Treatment of Hyperthyroidism in Patients With Graves' Disease and Moderate-to-severe and Active Graves' Orbitopathy (GO) Treated With Intravenous Glucocorticoids (ABLAGO Study)
- ClinicalTrials.gov ID
- NCT04776993
- Acronym / sponsor ID
- ABLAGO / ABLAGO
- Conditions
- Graves' Orbitopathy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- University of PisaUniversity, hospital or other
- Study start
- 2 Mar 2023 (actual)
- Primary completion
- 1 Sep 2024 (estimated)
- Study completion
- 1 Mar 2026 (estimated)
- First posted
- 2 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Graves' disease (GD) is the most frequent cause of hyperthyroidism in iodine sufficient countries and Graves' orbitopathy (GO) is its most common extrathyroidal manifestation. Restoration and maintenance of euthyroidism are imperative in Graves' disease patients with GO. The main treatment options for Graves' hyperthyroidism are antithyroid drugs, radioactive iodine (RAI), and surgery. Whether one or the other therapy for Graves' hyperthyroidism offers the best protection against GO is not established. The study is aimed at comparing the effects of a conservative approach (antithyroid drugs, ATDs, experimental arm) vs an ablative approach (radioiodine or total thyroidectomy) of thyroid treatment on the overall outcome of GO in patients with GD and moderate-to-severe and active GO treated with intravenous glucocorticoids.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methimazole | Experimental | Drug: MethimazoleAntithyroid drugs (at individualized dosage) for 72 weeks and a cumulative dose of 4.5 g of methylprednisolone divided into 12 weekly infusions |
| Thyroid ablation | Active comparator | Procedure: Radioiodine or thyroidectomyRadioiodine therapy or total thyroidectomy (according to ultrasound thyroid volume) and a cumulative dose of 4.5 g of methylprednisolone divided into 12 weekly infusions |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients willing and capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
- A diagnosis of Graves' disease based on the presence of hyperthyroidism associated with detectable anti-thyrotropic hormone (TSH) receptor autoantibodies (TRAb). Patients must be euthyroid under control on stable medical regimen and every effort will be made to maintain the euthyroid status for the entire duration of the clinical trial.
- Duration of Graves' disease shorter than 18 months
- A moderate-to-severe GO, defined as the presence of at least one of the following criteria in the most affected eye: an exophthalmos ≥2 mm compared with normal values for sex and race; presence of inconstant to constant diplopia; a lid retraction ≥2 mm
- Active GO: CAS ≥ 3 out of 7 points in the most affected eye. Taking into account severity (moderate-to-severe) and activity (CAS ≥ 3/7) of GO, patients are eligible for methylprednisolone treatment according to clinical practice.
Key exclusion criteria (11 listed)
- Optic neuropathy
- Previous therapy for Graves' disease with radioiodine or thyroidectomy
- Corticosteroids or other immunosuppressive treatment for GO or other reasons in the last 3 months.
- Previous surgical treatment and/or radiotherapy for GO
- Contraindications to GC: hypersensitivity to the active substance or to any of the excipients; uncontrolled hypertension, uncontrolled diabetes; history of peptic ulcer; urinary infections, glaucoma, systemic fungal infections, systemic infections unless appropriate therapy is employed, idiopathic thrombocytopenic purpura, cerebral edema associated with malaria.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethimazoleAlso: MMIMethimazole for 72 weeks | Drug | Methimazole |
| Radioiodine or thyroidectomyAlso: Thyroid ablationTreatment with radioiodine or with thyroidectomy | Procedure or surgery | Thyroid ablation |
Primary outcome
Overall GO outcome
Time frame: 24 weeks
Improvement is defined as change in two of the following outcome measures in at least one eye, without deterioration in any of the same measures in both eyes (compared to baseline): * Improvement in CAS by at least 2 points * Improvement in exophthalmos by at least 2 mm (Hertel exophthalmometer) * Improvement in lid aperture by at least 2 mm * Improvement in diplopia (disappearance or change in the degree) * Improvement of visual acuity by at least 0.2/1 Patients meeting the improvement criteria will be considered as "responders". All other patients will be considered as "non-responders".
4 secondary outcomes
Overall GO outcome
Time frame: 48 weeks
Overall GO outcome
Time frame: 72 weeks
Response of individual GO parameters: proptosis, CAS, eyelid width, diplopia, and visual acuity
Time frame: 24, 48 and 72 weeks
Quality of life questionnaire
Time frame: 24, 48 and 72 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Methimazole and Radioiodine or thyroidectomy in people with Graves' Orbitopathy, run by University of Pisa at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Michele Marino (+39050997346, michele.marino@med.unipi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall GO outcome (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2023.