Graves DiseaseNCT04391439
Heart Rhythm After Intravenous Methylprednisolone Administration
An observational study of Graves Disease and Graves Ophthalmopathy, run by Medical University of Warsaw.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graves Disease, Graves Ophthalmopathy, Heart Rhythm Disorder
- What is being tested?
- Intravenous Methylprednisolone
- Type of treatment
- Injection or infusion
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2011to 20 Feb 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients admitted to the clinic for routine treatment of active, moderate-to-severe GO
Who may be able to join
- active, moderate-to-severe GO according to EUGOGO classification
- euthyroidism
- completion of 12 IVMP pulses.
Who cannot join
- 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.
About this study
Official title: Increased Heart Rhythm in Response to High-dose Intravenous Methylprednisolone Pulse Therapy of Moderate-to-severe Graves' Orbitopathy
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).
Read the 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.
- Conditions
- Graves Disease, Graves Ophthalmopathy, Heart Rhythm Disorder, Hypertension, Blood Pressure, Heart Failure
- Being tested
- Intravenous Methylprednisolone
- Medical subject headings
- Graves Disease, Graves Ophthalmopathy, Hypertension, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous MethylprednisoloneDrug
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Intravenous Methylprednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
24-hour Holter ECG Monitoring - 1st pulse mean HR
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
Measured: 72 hours
24-hour Holter ECG Monitoring - 6th pulse mean HR
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
Measured: 72 hours
24-hour Holter ECG Monitoring - 12th mean HR
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
Measured: 72 hours
Secondary outcomes (7)
Serum potassium levels Day 0 - Day 1
Change in value of potassium between day before and day of 1st pulse of IVMP
Measured: 48 hours
Serum epinephrine levels Day 0 - Day 1
Change in value of epinephrine between day before and day of 1st pulse of IVMP
Measured: 48 hours
Serum norepinephrine levels Day 0 - Day 1
Change in value of norepinephrine between day before and day of 1st pulse of IVMP
Measured: 48 hours
Urine potassium levels Day 0
Change in value of potassium during the day of 1st pulse of IVMP
Measured: 24 hours
72-hour ambulatory blood pressure monitoring (ABPM) - 1st pulse mean BP
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
Measured: 72 hours
72-hour ambulatory blood pressure monitoring (ABPM) - 6th pulse mean BP
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
Measured: 72 hours
72-hour ambulatory blood pressure monitoring (ABPM) - 12th pulse mean BP
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
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2020
- Study start1 Jan 2011
- Primary completion20 Feb 2020
- Study completion20 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graves DiseaseStudies of the same condition, open and under way.
- More trials run by Medical University of WarsawThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Warsaw
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Piotr Miskiewicz, Medical University of Warsaw
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04391439
- Sponsor's protocol ID
- IVMPheartrate
- Status last verified
- May 2020
- First submitted
- 5 May 2020
- Last updated
- 18 May 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Increased Heart Rhythm in Response to High-dose Intravenous Methylprednisolone Pulse Therapy of Moderate-to-severe Graves' Orbitopathy
- ClinicalTrials.gov ID
- NCT04391439
- Acronym / sponsor ID
- IVMPheartrate
- Conditions
- Graves Disease, Graves Ophthalmopathy, Heart Rhythm Disorder, Hypertension, Blood Pressure, Heart Failure
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Medical University of WarsawUniversity, hospital or other
- Study start
- 1 Jan 2011 (actual)
- Primary completion
- 20 Feb 2020 (actual)
- Study completion
- 20 Feb 2020 (actual)
- First posted
- 18 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| active, moderate-to-severe GO | – | Drug: Intravenous 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients admitted to the clinic for routine treatment of active, moderate-to-severe GO
Key inclusion criteria (3 listed)
- active, moderate-to-severe GO according to EUGOGO classification
- euthyroidism
- completion of 12 IVMP pulses.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous Methylprednisolone | Drug | active, moderate-to-severe GO |
Primary outcome
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
7 secondary outcomes
Serum potassium levels Day 0 - Day 1
Time frame: 48 hours
Serum epinephrine levels Day 0 - Day 1
Time frame: 48 hours
Serum norepinephrine levels Day 0 - Day 1
Time frame: 48 hours
Urine potassium levels Day 0
Time frame: 24 hours
72-hour ambulatory blood pressure monitoring (ABPM) - 1st pulse mean BP
Time frame: 72 hours
72-hour ambulatory blood pressure monitoring (ABPM) - 6th pulse mean BP
Time frame: 72 hours
72-hour ambulatory blood pressure monitoring (ABPM) - 12th pulse mean BP
Time frame: 72 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2020.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Graves Disease and Graves Ophthalmopathy, run by Medical University of Warsaw.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 May 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
24-hour Holter ECG Monitoring - 1st pulse mean HR (time frame: 72 hours). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2020.