Heart Rhythm After Intravenous Methylprednisolone Administration

Sponsor

Medical University of Warsaw (Other)

Overall Status

Completed

CT.gov ID

NCT04391439

Collaborator

(none)

Enrollment

109.6

Actual Duration (Months)

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Graves Disease Graves Ophthalmopathy Heart Rhythm Disorder Hypertension Blood Pressure Heart Failure	Drug: Intravenous Methylprednisolone

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.

Study Design

Study Type:

Observational

Actual Enrollment :

40 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Increased Heart Rhythm in Response to High-dose Intravenous Methylprednisolone Pulse Therapy of Moderate-to-severe Graves' Orbitopathy

Actual Study Start Date :

Jan 1, 2011

Actual Primary Completion Date :

Feb 20, 2020

Actual Study Completion Date :

Feb 20, 2020

Arms and Interventions

Arm	Intervention/Treatment
active, moderate-to-severe GO Each 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).	Drug: Intravenous Methylprednisolone

Arm

Intervention/Treatment

active, moderate-to-severe GO

Each 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).

Drug: Intravenous Methylprednisolone

Outcome Measures

Primary Outcome Measures

24-hour Holter ECG Monitoring - 1st pulse mean HR [72 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 - 6th pulse mean HR [72 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
24-hour Holter ECG Monitoring - 12th mean HR [72 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

Secondary Outcome Measures

Serum potassium levels Day 0 - Day 1 [48 hours]
Change in value of potassium between day before and day of 1st pulse of IVMP
Serum epinephrine levels Day 0 - Day 1 [48 hours]
Change in value of epinephrine between day before and day of 1st pulse of IVMP
Serum norepinephrine levels Day 0 - Day 1 [48 hours]
Change in value of norepinephrine between day before and day of 1st pulse of IVMP
Urine potassium levels Day 0 [24 hours]
Change in value of potassium during the day of 1st pulse of IVMP
72-hour ambulatory blood pressure monitoring (ABPM) - 1st pulse mean BP [72 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 BP [72 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
72-hour ambulatory blood pressure monitoring (ABPM) - 12th pulse mean BP [72 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

Other Outcome Measures

Serum potassium levels Day 0 - Day 7 [7 days]
Change in value of potassium between day before and sixth day after 1st pulse of IVMP
Serum potassium levels Day 0 - Day 2 [72 hours]
Change in value of potassium between day of 1st IVMP and day after 1st IVMP, day before and day after 1st IVMP
Serum epinephrine levels Day 0 - Day 7 [7 days]
Change in value of epinephrine between day before and sixth day after 1st pulse of IVMP
Serum epinephrine levels Day 0 - Day 2 [72 hours]
Change in value of epinephrine between day of 1st IVMP and day after 1st IVMP, day before and day after 1st IVMP
Serum norepinephrine levels Day 0 - Day 7 [7 days]
Change in value of epinephrine between day before and sixth day after 1st pulse of IVMP
Serum norepinephrine levels Day 0 - Day 2 [72 hours]
Change in value of norepinephrine between day of 1st IVMP and day after 1st IVMP, day before and day after 1st IVMP
Urine potassium levels Day 1- Day 2 [48 hours]
Change in value of epinephrine between day of 1st IVMP and day after 1st pulse of IVMP
Urine potassium levels Day 3 - Day 7 [5 days]
Change in value of epinephrine between second and sixth day after 1st IVMP

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.