E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hypothyroidism and Acute Myocardial Infarction |
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E.1.1.1 | Medical condition in easily understood language |
Underactive thyroid and Heart Attack |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000891 |
E.1.2 | Term | Acute myocardial infarction |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
ThyrAMI-1: whether thyroid function at the time of heart attack is related to poorer heart disease outcomes.
ThyrAMI-2: to determine whether treatment of underactive thyroid with Levothyroxine following a heart attack improves heart muscle function. |
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E.2.2 | Secondary objectives of the trial |
ThyrAMI-1: to assess what proportion of individuals who have had a heart attack also have thyroid problems.
ThyrAMI-2: The secondary research questions are whether treatment of mild underactive thyroid following a heart attack improves clot size, blood vessel function, health status, quality of life and is safe. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For the observation study:
Adult males and females (aged 18 yrs or older).
Acute myocardial infarction diagnosed in the preceding 24 hours.
Participants in other research studies will be eligible for inclusion as this is an observational study.
For the interventional study:
Males and females aged between 18-75 yrs.
Serum TSH between 4.01 -10.00 mU/L with normal free thyroxine levels (9 – 25 pmol/L) on two occasions (on day of admission for heart attack (AMI) and 7-10 days after AMI).
Acute myocardial infarction diagnosed on admission to hospital (chest pain with dynamic ECG changes or increase troponin enzymes (at least a fourfold increase above normal range).
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E.4 | Principal exclusion criteria |
For the observation study:
Patients who are unable to provide informed consent.
Those with advanced malignancy (who are unlikely to survive for more than 6 months in the opinion of local investigator).
On medications that can affect thyroid function such as amiodarone, lithium, carbimazole and propylthiouracil. Patients on levothyroxine will be included but their results will be analysed separately.
For the interventional study:
Patients on medications affecting thyroid function (levothyroxine, carbimazole, propylthiouracil, amiodarone, lithium).
Patients who are unable to provide written informed consent.
Patients with advanced malignancy (who, in the opinion of the investigator, is unlikely to survive for more than 6 months).
Patients with sustained ventricular tachycardia requiring treatment which occurs >24hrs after myocardial re-perfusion/revascularisation.
Patients who have contra-indications to MR scanning (cardiac pacemaker, metallic heart valves, cochlear implants, coronary artery stents incompatible with MR scanning, etc.).
Patients who are unlikely or unwilling, in the opinion of the investigator, to attend for study specific visits.
Participants whose serum TSH is >10.0 or <4.0 on either occasion.
Patients who are already participating in another interventional study.
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E.5 End points |
E.5.1 | Primary end point(s) |
ThyrAMI-1 The association between thyroid function at the time of AMI (within 24 hours of diagnosis) with vascular outcomes (another AMI, coronary revascularisation or death due to ischaemic heart disease) over 24 months.
ThyrAMI-2 The primary outcome measure will be change in left ventricular ejection fraction as assessed by magnetic resonance imaging. Cardiac Magnetic Resonance (MR) is considered the gold standard for evaluating cardiac volumes and function. Gradient echo sequences provide a naturally high level of contrast between intra-cavitary blood and myocardium, thus allowing an accurate and reproducible determination of LV volumes, mass and calculation of stroke volume and ejection fraction. Cardiac MR imaging will be performed at the dedicated 3T MRI centre in Newcastle University. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
ThyrAMI-1 outcome assessed between time of AMI (within 24 hours of diagnosis) up until 24 months.
THyrAMI-2 outcome assessed starting within 21 days following AMI. AMI is date of diagnosis or the date of admission to hospital, whichever is later. Endpoint is 12 months.
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E.5.2 | Secondary end point(s) |
ThyrAMI-1 for all secondary endpoints, measurement will take place between time of AMI and 24 months post AMI.
ThyrAMI-2 for all secondary endpoints, measurement will take place at baseline and at 12 months. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
ThyrAMI-1: 24 months post AMI
ThyrAMI-2: 12 months post randomisation |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of study will be the last participant’s final study contact, at 53 weeks (+/- 7 days) post-randomisation. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |