Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Heart Rhythm After Intravenous Methylprednisolone Administration

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04391439
Recruitment Status : Completed
First Posted : May 18, 2020
Last Update Posted : May 18, 2020
Sponsor:
Information provided by (Responsible Party):
Piotr Miskiewicz, 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).

Condition or disease Intervention/treatment
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.

Layout table for study information
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 : January 1, 2011
Actual Primary Completion Date : February 20, 2020
Actual Study Completion Date : February 20, 2020


Group/Cohort 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



Primary Outcome Measures :
  1. 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

  2. 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

  3. 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 Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. Urine potassium levels Day 0 [ Time Frame: 24 hours ]
    Change in value of potassium during the day of 1st pulse of IVMP

  5. 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

  6. 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

  7. 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


Other Outcome Measures:
  1. Serum potassium levels Day 0 - Day 7 [ Time Frame: 7 days ]
    Change in value of potassium between day before and sixth day after 1st pulse of IVMP

  2. Serum potassium levels Day 0 - Day 2 [ Time Frame: 72 hours ]
    Change in value of potassium between day of 1st IVMP and day after 1st IVMP, day before and day after 1st IVMP

  3. Serum epinephrine levels Day 0 - Day 7 [ Time Frame: 7 days ]
    Change in value of epinephrine between day before and sixth day after 1st pulse of IVMP

  4. Serum epinephrine levels Day 0 - Day 2 [ Time Frame: 72 hours ]
    Change in value of epinephrine between day of 1st IVMP and day after 1st IVMP, day before and day after 1st IVMP

  5. Serum norepinephrine levels Day 0 - Day 7 [ Time Frame: 7 days ]
    Change in value of epinephrine between day before and sixth day after 1st pulse of IVMP

  6. Serum norepinephrine levels Day 0 - Day 2 [ Time Frame: 72 hours ]
    Change in value of norepinephrine between day of 1st IVMP and day after 1st IVMP, day before and day after 1st IVMP

  7. Urine potassium levels Day 1- Day 2 [ Time Frame: 48 hours ]
    Change in value of epinephrine between day of 1st IVMP and day after 1st pulse of IVMP

  8. Urine potassium levels Day 3 - Day 7 [ Time Frame: 5 days ]
    Change in value of epinephrine between second and sixth day after 1st IVMP


Biospecimen Retention:   Samples Without DNA
All assays were performed in sera obtained from venous blood samples and analysed immediately after blood sampling in The Endocrinology Research Laboratory in the hospital. All samples were centrifugated for plasma immediately after delivery (15 min; 1000 xg) and separated for both categories (EDTA and heparin) - 2 x 400 ul for test tubes with protease inhibitors and 4 x 500 ul with no additives. Then all assays were frozen immediately to -70°C.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients admitted to the clinic for routine treatment of active, moderate-to-severe GO
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.
Layout table for additonal information
Responsible Party: Piotr Miskiewicz, Assistant Professor, Medical University of Warsaw
ClinicalTrials.gov Identifier: NCT04391439    
Other Study ID Numbers: IVMPheartrate
First Posted: May 18, 2020    Key Record Dates
Last Update Posted: May 18, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The collected data will be shared in a publication. It includes all laboratory results from all points of evaluation, results of 72-hour Holter ECG and 72-hour ABPM.
Time Frame: The results of the study will be published in 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Graves Disease
Graves Ophthalmopathy
Arrhythmias, Cardiac
Eye Diseases
Cardiovascular Diseases
Heart Diseases
Exophthalmos
Orbital Diseases
Goiter
Thyroid Diseases
Endocrine System Diseases
Hyperthyroidism
Autoimmune Diseases
Immune System Diseases
Eye Diseases, Hereditary
Genetic Diseases, Inborn
Pathologic Processes
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents