Graves DiseaseNCT03590080
Impact of Intravenous Methylprednisolone Treatment on Blood Pressure
An observational study of Graves Disease and Graves Ophthalmopathy, run by Medical University of Warsaw.
Trial summary
Hypertension is common side effect of Cushing Syndrome (CS): in patients with endogenous CS and those treated with glucocorticosteroids (GCs). The impact of the intravenous GCs therapy on blood pressure (BP) remains unclear. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graves Disease, Graves Ophthalmopathy, Hypertension
- What is being tested?
- Methylprednisolone
- Type of treatment
- Injection or infusion
- How many people
- 32 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2011to 30 Dec 2015
- 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 at least first six 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: Blood Pressure Profile and NT-proBNP Dynamics in Response to Intravenous Methylprednisolone Pulse Therapy of Severe Graves' Orbitopathy
Hypertension is common side effect of Cushing Syndrome (CS): in patients with endogenous CS and those treated with glucocorticosteroids (GCs). The impact of the intravenous GCs therapy on blood pressure (BP) remains unclear. According to the European Group On Graves' Orbitopathy (EUGOGO), patients with active, severely symptomatic and sight-threatening Graves' orbitopathy (GO) should be treated with high dose intravenous methylprednisolone (IVMP) pulses. There are, however, reports of fatal side effects that may be associated with this therapy (e.g.: pulmonary embolism, myocardial infarction, severe cerebrovascular events, acute liver damage and sudden death). For this reason, the cumulative dose of IVMP should not exceed 8 g within each treatment course, and pulses should not be given on consecutive or alternate days, except for the case of dysthyroid optic neuropathy. A consensus on the monitoring of patients during and after IVMP pulse administration is not yet established. What is more, there is lack of paper regarding pattern of blood pressure at various time points during and after ivGCs administration. Thus, the investigators decided to evaluate acute changes of N-terminal pro-brain natriuretic peptide (NT-proBNP) as a marker of hemodynamic stress and to monitor BP before, during and after IVMP pulse administration. All of 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
Laboratory tests such as NT-proBNP, troponin I (TnI) and high - sensitivity C - reactive protein (hs-CRP) were performed before, 24 h and 48 h after IVMP during the following pulses: 1st, 6th and 12th. Patients underwent echocardiographic examination before 1st and after 12th pulse. 48-hours ambulatory blood pressure monitoring (ABPM) (for 24 hours before and 24 hours after IVMP) was done during the following pulses: 1st, 6th and 12th.
- Being tested
- Methylprednisolone
- Keywords
- Graves' Disease, Graves' Ophthalmopathy, Hypertension, Blood Pressure, Methylprednisolone, Glucocorticoids
- 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.
| 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: Methylprednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
NT-proBNP 1-24h
Change in value of NT-proBNP from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Measured: 24 hours
NT-proBNP 1-12w
Change in value of NT-proBNP from baseline (before administration of methylprednisolone) to the basic NT-proBNP before last pulse with methylprednisolone
Measured: 12 weeks
48-hour ambulatory blood pressure monitoring (ABPM)- 1 mean BP
Analysis of changes in mean blood pressure in ABPM between day before methylprednisolone administration and second day after first pulse of methylprednisolone administration
Measured: 48 hours
48-hour ambulatory blood pressure monitoring (ABPM)- 12 mean BP
Analysis of changes in mean blood pressure in ABPM between day before methylprednisolone administration and second day after 12th pulse of methylprednisolone administration
Measured: 12 weeks
48-hour ambulatory blood pressure monitoring (ABPM)- 1 max systolic BP
Analysis of changes in maximal systolic blood pressure in ABPM between day before methylprednisolone administration and second day after first pulse of methylprednisolone administration
Measured: 48 hours
48-hour ambulatory blood pressure monitoring (ABPM)- 12 max systolic BP
Analysis of changes in maximal systolic blood pressure in ABPM between day before methylprednisolone administration and second day after 12th pulse of methylprednisolone administration
Measured: 48 hours
echocardiographic examinations - median values of Ejection Fraction (EF)
Analysis of change in median values of EF between echocardiographic examinations before first methylprednisolone administration and after last pulse of methylprednisolone
Measured: 12 weeks
Secondary outcomes (3)
hs-CRP
Change in value of hs-CRP from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Measured: 24 hours
Biomarker of cardiomyocyte injury - TnI
Change in value of TnI from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Measured: 24 hours
NT-proBNP 1-48h
Change in value of NT-proBNP from baseline (before administration of methylprednisolone) to 48 hours after first intravenous pulse
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2018
- Study start1 Jan 2011
- Primary completion30 Dec 2015
- Study completion30 Dec 2015
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
- 32 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
- Investigators
- Piotr Miśkiewicz, MD, PhD, Principal investigator, Department of Endocrinology Medical University of Warsaw
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03590080
- Sponsor's protocol ID
- IVMPHeart
- Status last verified
- Jul 2018
- First submitted
- 30 Jun 2018
- Last updated
- 18 Jul 2018
- Results posted
- No
- Data monitoring committee
- 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 48 - hour ABPM and echocardiographic measurements
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Blood Pressure Profile and NT-proBNP Dynamics in Response to Intravenous Methylprednisolone Pulse Therapy of Severe Graves' Orbitopathy
- ClinicalTrials.gov ID
- NCT03590080
- Acronym / sponsor ID
- IVMPHeart
- Keywords
- Graves' Disease, Graves' Ophthalmopathy, Hypertension, Blood Pressure, Methylprednisolone, Glucocorticoids
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Medical University of WarsawUniversity, hospital or other
- Study start
- 1 Jan 2011 (actual)
- Primary completion
- 30 Dec 2015 (actual)
- Study completion
- 30 Dec 2015 (actual)
- First posted
- 18 Jul 2018 (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.
Hypertension is common side effect of Cushing Syndrome (CS): in patients with endogenous CS and those treated with glucocorticosteroids (GCs). The impact of the intravenous GCs therapy on blood pressure (BP) remains unclear. According to the European Group On Graves' Orbitopathy (EUGOGO), patients with active, severely symptomatic and sight-threatening Graves' orbitopathy (GO) should be treated with high dose intravenous methylprednisolone (IVMP) pulses. There are, however, reports of fatal side effects that may be associated with this therapy (e.g.: pulmonary embolism, myocardial infarction, severe cerebrovascular events, acute liver damage and sudden death). For this reason, the cumulative dose of IVMP should not exceed 8 g within each treatment course, and pulses should not be given on consecutive or alternate days, except for the case of dysthyroid optic neuropathy. A consensus on the monitoring of patients during and after IVMP pulse administration is not yet established. What is more, there is lack of paper regarding pattern of blood pressure at various time points during and after ivGCs administration. Thus, the investigators decided to evaluate acute changes of N-terminal pro-brain natriuretic peptide (NT-proBNP) as a marker of hemodynamic stress and to monitor BP before, during and after IVMP pulse administration. All of 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
Laboratory tests such as NT-proBNP, troponin I (TnI) and high - sensitivity C - reactive protein (hs-CRP) were performed before, 24 h and 48 h after IVMP during the following pulses: 1st, 6th and 12th. Patients underwent echocardiographic examination before 1st and after 12th pulse. 48-hours ambulatory blood pressure monitoring (ABPM) (for 24 hours before and 24 hours after IVMP) was done during the following pulses: 1st, 6th and 12th.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| active, moderate-to-severe GO | – | Drug: 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 at least first six 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 |
|---|---|---|
| Methylprednisolone | Drug | active, moderate-to-severe GO |
Primary outcome
NT-proBNP 1-24h
Time frame: 24 hours
Change in value of NT-proBNP from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
NT-proBNP 1-12w
Time frame: 12 weeks
Change in value of NT-proBNP from baseline (before administration of methylprednisolone) to the basic NT-proBNP before last pulse with methylprednisolone
48-hour ambulatory blood pressure monitoring (ABPM)- 1 mean BP
Time frame: 48 hours
Analysis of changes in mean blood pressure in ABPM between day before methylprednisolone administration and second day after first pulse of methylprednisolone administration
48-hour ambulatory blood pressure monitoring (ABPM)- 12 mean BP
Time frame: 12 weeks
Analysis of changes in mean blood pressure in ABPM between day before methylprednisolone administration and second day after 12th pulse of methylprednisolone administration
48-hour ambulatory blood pressure monitoring (ABPM)- 1 max systolic BP
Time frame: 48 hours
Analysis of changes in maximal systolic blood pressure in ABPM between day before methylprednisolone administration and second day after first pulse of methylprednisolone administration
48-hour ambulatory blood pressure monitoring (ABPM)- 12 max systolic BP
Time frame: 48 hours
Analysis of changes in maximal systolic blood pressure in ABPM between day before methylprednisolone administration and second day after 12th pulse of methylprednisolone administration
echocardiographic examinations - median values of Ejection Fraction (EF)
Time frame: 12 weeks
Analysis of change in median values of EF between echocardiographic examinations before first methylprednisolone administration and after last pulse of methylprednisolone
3 secondary outcomes
hs-CRP
Time frame: 24 hours
Biomarker of cardiomyocyte injury - TnI
Time frame: 24 hours
NT-proBNP 1-48h
Time frame: 48 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 Jul 2018.
- 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 48 - hour ABPM and echocardiographic measurements
Related trials for Graves Disease
Not yet recruiting
Impact of Restrictive Diets on Inflammation and Quality of Life in Autoimmune Thyroiditis
Thyroid Autoimmune Disease, Hashimoto's Thyroiditis
RecruitingPhase 3
A Study to Assess Efficacy and Safety of Efgartigimod PH20 SC PFS in Adult Participants With Graves' Disease
Graves' Disease, Graves Disease
RecruitingPhase 3
A Study to Assess Efficacy and Safety of Efgartigimod PH20 SC PFS in Adult Participants With Graves' Disease.
Graves Disease
Active, not recruitingPhase 4
Hydroxychloroquine in Mild Graves' Orbitopathy
Graves Ophthalmopathy
RecruitingPhase 2
A Study to Assess the Efficacy, Safety, and Tolerability of IMVT-1402 as Treatment for Adult Participants With Graves' Disease
Graves' Disease
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.
Piotr Miśkiewicz, MD, PhD principal investigator
Department of Endocrinology Medical University of Warsaw
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 Jul 2018. 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?
NT-proBNP 1-24h (time frame: 24 hours). The study lists 7 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 Jul 2018.