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Trial registered on ANZCTR


Registration number
ACTRN12621000237886
Ethics application status
Approved
Date submitted
23/12/2020
Date registered
5/03/2021
Date last updated
30/03/2022
Date data sharing statement initially provided
5/03/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Thyroid Replacement Options for Primary Hypothyroidism: -A Pilot Study
Scientific title
Thyroid Replacement Options-Pilot Study. To assess the feasibility and design of a large-scale Thyroid Replacement Options study of Australians aged 18-60 years who are dissatisfied with their wellbeing on levothyroxine (LT4) replacement for primary hypothyroidism.
Secondary ID [1] 303062 0
P3647
Universal Trial Number (UTN)
Trial acronym
THYRO Pilot
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypothyroidism 320136 0
Condition category
Condition code
Metabolic and Endocrine 318078 318078 0 0
Thyroid disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Brief name:
Thyroid hormones
Arm 1- Levothyroxine (LT4)/ Liothyronine (LT3) combination
Arm 2- Desiccated thyroid extract

International Non-proprietary Name (INN)
Arm 1
Levothyroxine (LT4 ) - (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid
Liothyronine (LT3) - (2S)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoic acid
Arm 2 - The active pharmaceutical ingredients in desiccated thyroid extract are LT4 and LT3. The INN is the same as for Arm 1.
Levothyroxine (LT4 ) - (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid
Liothyronine (LT3) - (2S)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoic acid
Dose administration
Participants will sequentially receive two 21 week phases of oral treatment with twice daily thyroid hormones tablets (i) LT4/LT3 combination, and (ii) desiccated thyroid extract. Dose adjustment will occur seven-weekly, based on results of serum thyroid function testing. Dosing of medications will be titrated to target TSH between 0.3-4.0 mU/L, and for free T4 and free T3 serum levels to be in the normal range (free T4 10-20 pmol/L, free T3 2.8-6.8 pmol/L) . Dosing will be increased or decreased in 25 mcg equivalent doses for levothyroxine. If thyroid function tests show under-treatment, the dose will be increased. If thyroid function tests show over-treatment, the dose will be decreased. We will monitor adherence to the intervention by asking participants to bring study medication to each visit. Pill counts will be performed every 7 weeks to compare with expected number of unused interventional product. At the end of each 21 week treatment phase any unused medication will be returned to the hospital pharmacy for destruction.
Intervention code [1] 319353 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 326067 0
Feasibility - recruitment rate as assessed by study database.
Timepoint [1] 326067 0
At 42 weeks post enrolment of the last enrolled participant.
Primary outcome [2] 326385 0
Feasibility - adherence to treatment regime as assessed by study-specific questionnaire
Timepoint [2] 326385 0
Every 7 weeks post commencement of intervention.
Primary outcome [3] 326386 0
Design - participant satisfaction with protocol measured with study specific questionnaire.
Timepoint [3] 326386 0
Every 7 weeks post commencement of intervention.
Secondary outcome [1] 390013 0
To assess the number of dose adjustments required for stable thyroid function using a dose adjustment algorithm as assessed by the study database.
Timepoint [1] 390013 0
At 21 weeks and 42 weeks post enrolment of the last enrolled participant.
Secondary outcome [2] 390014 0
Percentage of thyroid function tests with overt abnormalities (out-of-range thyroid hormone and serum TSH concentrations) on blood tests as assessed by study database.
Timepoint [2] 390014 0
At 21 weeks and 42 weeks post enrolment of the last enrolled participant.
Secondary outcome [3] 390015 0
Adverse events occurring in participants during each study phase. Participants may contact the study to report an adverse event– they will be provided with a wallet sized card including the telephone number to facilitate this. Adverse events will be recorded by the study team every 7 weeks after commencement of treatment as part of the clinical assessment measures done by the study team. All adverse events will be assessed using MeDRA code.
Timepoint [3] 390015 0
Every 4 weeks post commencement of intervention phase a report of adverse events will be compiled.
Secondary outcome [4] 391271 0
Primary Outcome: design - completeness of data as assessed by study database
Timepoint [4] 391271 0
At 42 weeks post enrolment of the last enrolled participant.
Secondary outcome [5] 391272 0
Primary outcome: Design - adherence to study protocol as assessed by study-specific questionnaire.
Timepoint [5] 391272 0
At 42 weeks post enrolment of the last enrolled participant.
Secondary outcome [6] 391273 0
Thyroid specific quality of life scores, measured with ThyPRO-39.
Timepoint [6] 391273 0
At 21 weeks and 42 weeks post enrolment, compared to baseline measure.
Secondary outcome [7] 392531 0
Design - staff satisfaction with protocol measured with study specific questionnaire.
Timepoint [7] 392531 0
Every 7 weeks post commencement of intervention.

Eligibility
Key inclusion criteria
- Provide signed and dated informed consent form
- Willing to comply with all study procedures for the duration of the study
- Aged 18-60 years
- Have confirmed history of hypothyroidism (documented in medical record or confirmed by usual treating medical practitioner), either previous biochemical primary hypothyroidism, total thyroidectomy, or radioiodine ablation
- Currently taking LT4 (without any other thyroid hormone products) at a dose greater than or equal to 100 mcg daily of brand names Oroxine or Eutroxsig
- Have had recorded serum TSH concentration between 0.3 and 4.0 mU/L within the last three months of the screening visit, or completed after Screening Visit on their current LT4 dose and prior to being enrolled into the trial.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
An individual who meets any of the below criteria will be excluded from participation in the study:
- Hypopituitarism
- History of thyroid cancer requiring suppression of TSH concentration
- Any active malignancy
- History of cardiac disease (coronary artery disease, arrhythmia, or heart failure)
- History of cirrhosis
- History of chronic kidney disease, stage 3 or higher
- Current T3-containing treatment
- Currently taking LT4 with brand name Eltroxin
- Planned or current pregnancy within the trial period
- Drug treatment known to affect thyroid hormone metabolism (including amiodarone, cholestyramine, systemic corticosteroids, propranolol, phenytoin, phenobarbital, carbamazepine, lithium, rifampicin, or biotin-containing supplements)
- Concurrent participation in another clinical trial
- Unable to provide consent
- Unable to read sufficiently to perform study tasks (i.e., study questionnaires)
- Significant concerns from the study team about the potential participant’s ability to complete, or safety during, the trial

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Sequential treatment open label
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
15/04/2021
Actual
17/05/2021
Date of last participant enrolment
Anticipated
15/07/2021
Actual
16/12/2021
Date of last data collection
Anticipated
31/12/2022
Actual
Sample size
Target
40
Accrual to date
Final
38
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 18254 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 32317 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 307469 0
Government body
Name [1] 307469 0
Queensland Government - Queensland Advancing Clinical Research Fellowships
Country [1] 307469 0
Australia
Primary sponsor type
Other
Name
QIMR Berghofer Medical Research Institute
Address
300 Herston Road, Herston, Brisbane, QLD, 4006
Australia
Country
Australia
Secondary sponsor category [1] 308155 0
None
Name [1] 308155 0
Address [1] 308155 0
Country [1] 308155 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307546 0
The QIMR Berghofer Human Research Ethics Committee
Ethics committee address [1] 307546 0
300 Herston Rd
Herston QLD 4006
Australia
Ethics committee country [1] 307546 0
Australia
Date submitted for ethics approval [1] 307546 0
Approval date [1] 307546 0
18/12/2020
Ethics approval number [1] 307546 0
P3647

Summary
Brief summary
The overall aim of this research project is to conduct an open label sequential treatment pilot study to assess alternate thyroid replacement treatments to standard levothyroxine (LT4) treatment. Participants will be aged 18-60 years taking greater than or equal to 100mcg daily LT4 monotherapy for hypothyroidism at stable dose. Participants will receive 21 weeks of levotriiodothyronine/ liothyronine (LT4/LT3) combination treatment followed by 21 weeks of desiccated thyroid extract. Dose adjustment will occur 7-weekly, based on results of serum thyroid function testing. The primary outcome of the pilot study is to assess the feasibility and design of a large-scale randomized trial of thyroid hormone therapies with specific trial design aspects to be studied including recruitment; adherence to treatment regimen; participant and staff satisfaction with protocol; completeness of data; and adherence to study protocol. The secondary outcome is to assess the number of dose adjustments required for stable thyroid function using a dose adjustment algorithm. Participant reported outcomes will look at the difference in thyroid-specific quality of life scores measured at the end of each study phase compared with their baseline score.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 107622 0
A/Prof Donald McLeod
Address 107622 0
QIMR Berghofer Medical Research Institute 300 Herston Road,
Herston, QLD 4006
Country 107622 0
Australia
Phone 107622 0
+61 7 3362 0286
Fax 107622 0
Email 107622 0
[email protected]
Contact person for public queries
Name 107623 0
Cathy Baxter
Address 107623 0
QIMR Berghofer Medical Research Institute
300 Herston Road,
Herston, QLD 4006 Australia
Country 107623 0
Australia
Phone 107623 0
+61 7 3845 3557
Fax 107623 0
Email 107623 0
[email protected]
Contact person for scientific queries
Name 107624 0
Donald McLeod
Address 107624 0
QIMR Berghofer Medical Research Institute 300 Herston Road,
Herston, QLD 4006
Country 107624 0
Australia
Phone 107624 0
+61 7 3362 0286
Fax 107624 0
Email 107624 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The trial team does not intend on making individual participant data public


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.