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Heart Rhythm After Intravenous Methylprednisolone Administration

Completed
Conditions
Heart Rhythm Disorder
Blood Pressure
Graves Ophthalmopathy
Hypertension
Graves Disease
Heart Failure
Interventions
Registration Number
NCT04391439
Lead Sponsor
Medical University of Warsaw
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
40
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.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
active, moderate-to-severe GOIntravenous MethylprednisoloneEach participant received IVMP according to EUGOGO recommendations (cumulative dose of methylprednisolone 4.5 g, treatment duration 12 weeks in single weekly intravenous pulses, first 6 weeks 0.5g of IVMP, next 6 weeks 0.25g of IVMP).
Primary Outcome Measures
NameTimeMethod
24-hour Holter ECG Monitoring - 1st pulse mean HR72 hours

Analysis of changes in mean HR between day before and day of 1st pulse of IVMP, day of 1st IVMP and day after 1st IVMP, day before and day after 1st IVMP

24-hour Holter ECG Monitoring - 12th mean HR72 hours

Analysis of changes in mean HR between day before and day of 12th pulse of IVMP, day of 12th IVMP and day after 12th IVMP, day before and day after 12th IVMP

24-hour Holter ECG Monitoring - 6th pulse mean HR72 hours

Analysis of changes in mean HR between day before and day of 6th pulse of IVMP, day of 6th IVMP and day after 6th IVMP, day before and day after 6th IVMP

Secondary Outcome Measures
NameTimeMethod
72-hour ambulatory blood pressure monitoring (ABPM) - 12th pulse mean BP72 hours

Analysis of changes in mean BP between day before and day of 12th pulse of IVMP, day of 12th IVMP and day after 12th IVMP, day before and day after 12th IVMP

Serum potassium levels Day 0 - Day 148 hours

Change in value of potassium between day before and day of 1st pulse of IVMP

Serum norepinephrine levels Day 0 - Day 148 hours

Change in value of norepinephrine between day before and day of 1st pulse of IVMP

Urine potassium levels Day 024 hours

Change in value of potassium during the day of 1st pulse of IVMP

72-hour ambulatory blood pressure monitoring (ABPM) - 1st pulse mean BP72 hours

Analysis of changes in mean BP between day before and day of 1st pulse of IVMP, day of 1st IVMP and day after 1st IVMP, day before and day after 1st IVMP

72-hour ambulatory blood pressure monitoring (ABPM) - 6th pulse mean BP72 hours

Analysis of changes in mean BP between day before and day of 6th pulse of IVMP, day of 6th IVMP and day after 6th IVMP, day before and day after 6th IVMP

Serum epinephrine levels Day 0 - Day 148 hours

Change in value of epinephrine between day before and day of 1st pulse of IVMP

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