Heart Rhythm After Intravenous Methylprednisolone Administration

Overview

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 6×0.5g followed by 6×0.25g every week).

Full Title of Study: “Increased Heart Rhythm in Response to High-dose Intravenous Methylprednisolone Pulse Therapy of Moderate-to-severe Graves’ Orbitopathy”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: February 20, 2020

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.

Interventions

  • Drug: Intravenous Methylprednisolone

Arms, Groups and Cohorts

  • 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).

Clinical Trial Outcome Measures

Primary Measures

  • 24-hour Holter ECG Monitoring – 1st pulse mean HR
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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 Measures

  • Serum potassium levels Day 0 – Day 1
    • Time Frame: 48 hours
    • Change in value of potassium between day before and day of 1st pulse of IVMP
  • Serum epinephrine levels Day 0 – Day 1
    • Time Frame: 48 hours
    • Change in value of epinephrine between day before and day of 1st pulse of IVMP
  • Serum norepinephrine levels Day 0 – Day 1
    • Time Frame: 48 hours
    • Change in value of norepinephrine between day before and day of 1st pulse of IVMP
  • Urine potassium levels Day 0
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Medical University of Warsaw
  • Provider of Information About this Clinical Study
    • Principal Investigator: Piotr Miskiewicz, Assistant Professor – Medical University of Warsaw

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