Clinical trial NCT04391439: Heart Rhythm After Intravenous Methylprednisolone Administration
Official title: Increased Heart Rhythm in Response to High-dose Intravenous Methylprednisolone Pulse Therapy of Moderate-to-severe Graves' Orbitopathy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Graves Disease
Graves Ophthalmopathy
Heart Rhythm Disorder
Hypertension
Blood Pressure
Heart Failure
Lead sponsor: Medical University of Warsaw
Sponsor class: OTHER
First posted: 2020-05-18
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients admitted to the clinic for routine treatment of active, moderate-to-severe GO

Brief summary: High doses of intravenous (iv.) glucocorticoids (GCs) are commonly used as a treatment for many autoimmune and inflammatory disorders. According to the European Group on Graves' Orbitopathy (EUGOGO) guidelines, intravenous methylprednisolone (IVMP) is an accepted first-line agent for active, moderate-to-severe and very severe Graves' orbitopathy (GO). This treatment is proven to be more efficient and safer than oral GCs. However, some patients may experience adverse cardiovascular effects during the administration of iv. GCs, which in rare cases may even be fatal. There are limited data, mostly obtained from case reports, reporting the occurrence of cardiac arrhythmias, acute myocardial infarction or heart failure. Increased heart rhythm (HR) has drawn attention of researchers as a possible adverse effect correlated with IVMP. During this study, investigators performed 72-hours of Holter ECG and ambulatory blood pressure monitoring (ABPM) to evaluate the impact of IVMP on patients with moderate-to-severe GO, concerning HR and blood pressure (BP) changes. In order to elucidate possible mechanism of observed changes, researchers investigated the level of potassium in serum and urine and catecholamines (epinephrine, norepinephrine) in serum. All patients were treated routinely according to EUGOGO recommendations with standard doses of methylprednisolone with standard recommended schedule. Inclusion criterion for the therapy was according to EUGOGO guidelines active, moderate-to-severe and active GO (12 pulses of IVMP 6x0.5g followed by 6x0.25g every week).

Detailed description: The clinical status of patients was evaluated before each pulse, including blood pressure monitoring, glucose level monitoring and symptoms of infection. HR and BP was measured continuously for 3 consecutive days (the day before, the day of IVMP and the day after IVMP) during 1st, 6th and 12th IVMP pulse, using 24-hour Holter ECG and ABMP. Serum laboratory tests for potassium, epinephrine and norepinephrine were measured 3 times the day before and the day of first IVMP pulse and 1 time the second and sixth day after 1st IVMP. Additionally, urine samples for potassium were collected 5 times the day of first IVMP pulse and 1 time the second and sixth day after 1st IVMP.

Eligibility criteria: Inclusion Criteria:

* active, moderate-to-severe GO according to EUGOGO classification
* euthyroidism
* completion of 12 IVMP pulses.

Exclusion Criteria:

* cardiovascular morbidity (such as chronic heart failure and/or coronary heart disease)
* uncontrolled hypertension (defined as systolic blood pressure (SBP) more than 140 mmHg and/or diastolic blood pressure (DBP) more than 90 mmHg)
* contraindications to IVMP therapy
* previous GCs treatment in the last 6 months.

Primary outcomes:
measure: 24-hour Holter ECG Monitoring - 1st pulse mean HR
timeFrame: 72 hours
measure: 24-hour Holter ECG Monitoring - 6th pulse mean HR
timeFrame: 72 hours
measure: 24-hour Holter ECG Monitoring - 12th mean HR
timeFrame: 72 hours
Secondary outcomes:
measure: Serum potassium levels Day 0 - Day 1
timeFrame: 48 hours
measure: Serum epinephrine levels Day 0 - Day 1
timeFrame: 48 hours
measure: Serum norepinephrine levels Day 0 - Day 1
timeFrame: 48 hours
measure: Urine potassium levels Day 0
timeFrame: 24 hours
measure: 72-hour ambulatory blood pressure monitoring (ABPM) - 1st pulse mean BP
timeFrame: 72 hours
measure: 72-hour ambulatory blood pressure monitoring (ABPM) - 6th pulse mean BP
timeFrame: 72 hours
measure: 72-hour ambulatory blood pressure monitoring (ABPM) - 12th pulse mean BP
timeFrame: 72 hours
Other outcomes:
measure: Serum potassium levels Day 0 - Day 7
timeFrame: 7 days
measure: Serum potassium levels Day 0 - Day 2
timeFrame: 72 hours
measure: Serum epinephrine levels Day 0 - Day 7
timeFrame: 7 days
measure: Serum epinephrine levels Day 0 - Day 2
timeFrame: 72 hours
measure: Serum norepinephrine levels Day 0 - Day 7
timeFrame: 7 days
measure: Serum norepinephrine levels Day 0 - Day 2
timeFrame: 72 hours
measure: Urine potassium levels Day 1- Day 2
timeFrame: 48 hours
measure: Urine potassium levels Day 3 - Day 7
timeFrame: 5 days
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