Ultrasound-guided Radiofrequency Ablation versus radioactive Iodine as treatment for Hyperthyroidism caused by Solitary Autonomous Thyroid Nodules (RABITO study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rijnstate Ziekenhuis Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

Decision date (initial)

2025-01-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515602-34-01

EudraCT number

2021-001941-11

ClinicalTrials.gov

NCT05142904

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To compare the one-year incidence of irreversible hypothyroidism after RAI or RFA treatment for HTN

Secondary objectives 7

1. To compare the one-year outcome of RFA or RAI treatment with respect to cure rate, nodal volume reduction, fractional nodal uptake, adverse effects, (thyroid function related) quality of life (QoL), and costs.
2. To assess whether RFA is cost-effective compared to RAI one year after treatment, based on collected data, and over a 10-year time horizon using a health economic state transition model.
3. To assess course of thyroid function and comparison of results of RFA and RAI treatment during a follow-up of 5 years.
4. To assess patient experiences and preferences in both RFA and RAI treatment
5. To compare outcomes on thyroid function of local standard practices of RAI treatment with nationally standardized RAI treatment
6. Facilitators and barriers for implementation of the treatment RFA or RAI in daily clinical practice beyond the controlled trial setting.
7. To assess treatment related thyroiditis.

Conditions and MedDRA coding

Hyperactive thyroid nodules

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Age > 18 years
2. Hyperthyroidism or subclinical hyperthyroidism caused by a solitary hyperactive thyroid nodule (HTN), either located in an otherwise normal thyroid gland, or in a multinodular goitre (MNG), with a diagnosis based on the following characteristics: o Blood TSH level below the lower limit of normal, and associated with either normal or elevated FT4 and FT3/T3 levels o Anti-TSH antibody negative o Solitary HTN confirmed by a diagnostic I-123 or I-131scintigraphy* , corresponding with a well demarcated thyroid node on ultrasound, cystic degeneration < 75%, nodule size <50 mm.
3. Treatment with RAI indicated, and eligible for RFA treatment
4. Signed informed consent

Exclusion criteria 9

1. Multifocal HTN: These patients should be treated according the current standard of care: RAI, surgery or ATD treatment.
2. HTN > 50 mm: There is some evidence to suggest that nodule size adversely affects the efficacy of RAI and RFA. Therefore, surgery is recommended as the option of first choice in such cases.
3. Insufficient suppression of thyroid tissue on thyroid scintigraphy. Fractional uptake will be determined by the Rijnstate research team. One region of interest (ROI) will be drawn around the whole thyroid and a second ROI around the hot nodule. The counts in these ROI’s will be divided and using a cut-off of ≥0.85 of uptake in the ROI of the nodule.
4. Medical history of Graves disease, I-131 treatment, RFA of the same nodule or thyroid malignancy
5. Presence of a medical device susceptible to disturbances caused by RFA generated currents.
6. Patients with physical or behavioural disorders that preclude safe isolation in radiation protection rooms, or safe RFA procedure under local or general anesthesia.
7. Patients with dysphagia, oesophageal stenosis, active gastritis, gastric erosion, a peptic ulcer or impaired gastro-intestinal motility.
8. Uncorrectable haemorrhagic diathesis.
9. Pregnant or breastfeeding women.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Cumulative incidence of irreversible hypothyroidism in the first year after intervention. Irreversible primary hypothyroidism is defined as: 1) (A)symptomatic elevation of TSH levels in the range of 5 - 10 mU/L for at least 10-12 weeks and without signs of recovery, confirmed by repeated measurements; or as (a)symptomatic hypothyroidism with TSH levels > 10 mU/L for more than 4 weeks, without signs of recovery, confirmed on at least two separate occasions.

Secondary endpoints 12

1. Cure rate at 1 year, complete cure is defined as a normalization of TSH, FT4 and FT3 /T3levels.
2. Thyroid nodule volume assessed by ultrasound at baseline, 6, and 12 months.
3. Fractional nodal uptake assessed by I-123 or I-131 scintigraphy, at baseline and 12 months.
4. Thyroid antibodies at 0 and 12 months, to monitor treatment-related autoimmunity.
5. Treatment related adverse events, number of adverse and serious adverse events at 6 weeks, and 3, 6 and 12 months.
6. Thyroid related quality of life, assessed by ThyPro questionnaire at baseline, and 6 and 12 months after treatment.
7. Health outcomes and quality of life at one year, based on the European QoL-5 Dimensions (EQ-5D-5L) questionnaire
8. Use of health care resources during the first year after treatment, according to medical records, iMCQ and iPCQ.
9. Cumulative costs at 1 year
10. Cost-effectiveness at 1 year is determined as the incremental costs in Euros per quality adjusted life year (QALY), assessed by the European QoL-5 Dimensions (EQ-5D-5L) at baseline and 6 weeks, 3, 6, 9 and 12 months after treatment and use of health care resources during the first 12 months
11. Course of thyroid function as assessed by TSH, FT4 and FT3 at baseline and during a one year follow-up with an extension of follow-up up to 5 years
12. Short-term patient satisfaction assessed by interviews, a satisfaction questionnaire, pain scoring by visual analog scale (VAS).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rijnstate Ziekenhuis Stichting

Sponsor organisation

Rijnstate Ziekenhuis Stichting

Address

Wagnerlaan 55

City

Arnhem

Postcode

6815 AD

Country

Netherlands

Scientific contact point

Organisation

Rijnstate Ziekenhuis Stichting

Contact name

Rabito study team

Public contact point

Organisation

Rijnstate Ziekenhuis Stichting

Contact name

Rabito study team

Locations

1 EU/EEA country · 14 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications