Study protocol: a randomised controlled trial on the clinical effects of levothyroxine treatment for subclinical hypothyroidism in people aged 80 years and over.
- Du Puy RS Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.
- Postmus I Department of Gerontology and Geriatrics (C7-Q), Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
- Stott DJ Geriatric Medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
- Blum MR Department of General Internal Medicine, Bern University Hospital, University of Bern, Bern, Switzerland.
- Poortvliet RKE Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.
- Den Elzen WPJ Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands.
- Peeters RP Department of Internal Medicine, Erasmus University Medical Centre, Rotterdam, the Netherlands.
- van Munster BC Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands.
- Wolffenbuttel BHR Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
- Westendorp RGJ Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
- Kearney PM Department of Epidemiology and Public Health, University College Cork, Cork, Ireland.
- Ford I Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
- Kean S Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
- Messow CM Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
- Watt T Department of Internal Medicine, Copenhagen University Hospital Herlev, Gentofte, Denmark.
- Jukema JW Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
- Dekkers OM Department of Endocrinology and metabolic disorders, Leiden University Medical Center, Leiden, the Netherlands.
- Smit JWA Radboud University Medical Center, Nijmegen, the Netherlands.
- Rodondi N Department of General Internal Medicine, Bern University Hospital, University of Bern, Bern, Switzerland.
- Gussekloo J Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.
- Mooijaart SP Department of Gerontology and Geriatrics (C7-Q), Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands. S.P.Mooijaart@lumc.nl.
- 2018-09-21
Published in:
- BMC endocrine disorders. - 2018
80-plus
Levothyroxine
Quality of life
Randomised controlled trial
Subclinical hypothyroidism
Age Factors
Aged, 80 and over
Double-Blind Method
Female
Follow-Up Studies
Humans
Hypothyroidism
Male
Netherlands
Thyroxine
Treatment Outcome
English
BACKGROUND
Subclinical hypothyroidism is common in older people and its contribution to health and disease needs to be elucidated further. Observational and clinical trial data on the clinical effects of subclinical hypothyroidism in persons aged 80 years and over is inconclusive, with some studies suggesting harm and some suggesting benefits, translating into equipoise whether levothyroxine therapy provides clinical benefits. This manuscript describes the study protocol for the Institute for Evidence-Based Medicine in Old Age (IEMO) 80-plus thyroid trial to generate the necessary evidence base.
METHODS
The IEMO 80-plus thyroid trial was explicitly designed as an ancillary experiment to the Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism randomised placebo controlled Trial (TRUST) with a near identical protocol and shared research infrastructure. Outcomes will be presented separately for the IEMO and TRUST 80-plus groups, as well as a pre-planned combined analysis of the 145 participants included in the IEMO trial and the 146 participants from the TRUST thyroid trial aged 80 years and over. The IEMO 80-plus thyroid trial is a multi-centre randomised double-blind placebo-controlled parallel group trial of levothyroxine treatment in community-dwelling participants aged 80 years and over with persistent subclinical hypothyroidism (TSH ≥4.6 and ≤ 19.9 mU/L and fT4 within laboratory reference ranges). Participants are randomised to levothyroxine 25 or 50 micrograms daily or matching placebo with dose titrations according to TSH levels, for a minimum follow-up of one and a maximum of three years. Primary study endpoints: hypothyroid physical symptoms and tiredness on the thyroid-related quality of life patient-reported outcome (ThyPRO) at one year. Secondary endpoints: generic quality of life, executive cognitive function, handgrip strength, functional ability, blood pressure, weight, body mass index, and mortality. Adverse events will be recorded with specific interest on cardiovascular endpoints such as atrial fibrillation and heart failure.
DISCUSSION
The combined analysis of participants in the IEMO 80-plus thyroid trial with the participants aged over 80 in the TRUST trial will provide the largest experimental evidence base on multimodal effects of levothyroxine treatment in 80-plus persons to date.
TRIAL REGISTRATION
Nederlands (Dutch) Trial Register: NTR3851 (12-02-2013), EudraCT: 2012-004160-22 (17-02-2013), ABR-41259.058.13 (12-02-2013).
Subclinical hypothyroidism is common in older people and its contribution to health and disease needs to be elucidated further. Observational and clinical trial data on the clinical effects of subclinical hypothyroidism in persons aged 80 years and over is inconclusive, with some studies suggesting harm and some suggesting benefits, translating into equipoise whether levothyroxine therapy provides clinical benefits. This manuscript describes the study protocol for the Institute for Evidence-Based Medicine in Old Age (IEMO) 80-plus thyroid trial to generate the necessary evidence base.
METHODS
The IEMO 80-plus thyroid trial was explicitly designed as an ancillary experiment to the Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism randomised placebo controlled Trial (TRUST) with a near identical protocol and shared research infrastructure. Outcomes will be presented separately for the IEMO and TRUST 80-plus groups, as well as a pre-planned combined analysis of the 145 participants included in the IEMO trial and the 146 participants from the TRUST thyroid trial aged 80 years and over. The IEMO 80-plus thyroid trial is a multi-centre randomised double-blind placebo-controlled parallel group trial of levothyroxine treatment in community-dwelling participants aged 80 years and over with persistent subclinical hypothyroidism (TSH ≥4.6 and ≤ 19.9 mU/L and fT4 within laboratory reference ranges). Participants are randomised to levothyroxine 25 or 50 micrograms daily or matching placebo with dose titrations according to TSH levels, for a minimum follow-up of one and a maximum of three years. Primary study endpoints: hypothyroid physical symptoms and tiredness on the thyroid-related quality of life patient-reported outcome (ThyPRO) at one year. Secondary endpoints: generic quality of life, executive cognitive function, handgrip strength, functional ability, blood pressure, weight, body mass index, and mortality. Adverse events will be recorded with specific interest on cardiovascular endpoints such as atrial fibrillation and heart failure.
DISCUSSION
The combined analysis of participants in the IEMO 80-plus thyroid trial with the participants aged over 80 in the TRUST trial will provide the largest experimental evidence base on multimodal effects of levothyroxine treatment in 80-plus persons to date.
TRIAL REGISTRATION
Nederlands (Dutch) Trial Register: NTR3851 (12-02-2013), EudraCT: 2012-004160-22 (17-02-2013), ABR-41259.058.13 (12-02-2013).
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1186/s12902-018-0285-8
- PMID 30231866
- Persistent URL
- https://sonar.ch/global/documents/58174
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