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Randomized Controlled Trial
. 2018 Sep 19;18(1):67.
doi: 10.1186/s12902-018-0285-8.

Study Protocol: A Randomised Controlled Trial on the Clinical Effects of Levothyroxine Treatment for Subclinical Hypothyroidism in People Aged 80 Years and Over

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Free PMC article
Randomized Controlled Trial

Study Protocol: A Randomised Controlled Trial on the Clinical Effects of Levothyroxine Treatment for Subclinical Hypothyroidism in People Aged 80 Years and Over

R S Du Puy et al. BMC Endocr Disord. .
Free PMC article

Abstract

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).

Keywords: 80-plus; Levothyroxine; Quality of life; Randomised controlled trial; Subclinical hypothyroidism.

Conflict of interest statement

Ethics approval and consent to participate

For the Netherlands site the study was approved by the Medical Ethical Committee on Research Involving Human Subjects (CCMO). For the Switzerland site the study was approved by the Bern ethical board and by the Swiss competent authority for drugs (Swissmedic). All participants provided written informed consent for both the screening and the participation phase (Additional files 2 and 3).

Consent for publication

Not applicable.

Competing interests

ZonMw and the Swiss National Science Foundation, as the funder, had no role in the design and conduct of the study nor in the preparation, review or approval of the manuscript. Merck KGaA provided the study medication and matching placebos without recompense. Merck KGaA was not involved in the design, funding or execution of the study or manuscript. The authors declare that they have no competing interest.

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