Graves' DiseaseNCT03535090
Coagulation After Intravenous Methylprednisolone Administration
An observational study of Graves' Disease and Graves Ophthalmopathy, run by Piotr Miskiewicz.
Trial summary
The alterations of coagulation and fibrinolysis parameters have been described in patients with endogenous Cushing's syndrome (CS) and those treated with glucocorticosteroids (GCs). The change in hemostatic process is associated with an increased risk of venous thromboembolic events (VTE) and pulmonary embolism (PE). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graves' Disease, Graves Ophthalmopathy, Blood Coagulation
- What is being tested?
- Methylprednisolone
- Type of treatment
- Injection or infusion
- How many people
- 26 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2011to 31 Dec 2014
- 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
- Adult, Older adult
Study population: Patients admitted to the Endocrine Department
Who may be able to join
- active, moderate-to-severe Graves' orbitopathy according to EUGOGO classification
- euthyroidism for at least 1 month
- completion of at least first six IVMP pulses
Who cannot join
- medical history of thromboembolic events
- cardiovascular morbidity (chronic heart failure, cardiovascular heart disease)
- uncontrolled hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg)
- liver disease (>3x increase of alanine aminotransferase and/or aspartate aminotransferase)
- active inflammation
- nephritic syndrome
Show all 11Show fewer
- active neoplastic disease
- previous GCs therapy within the last 6 months
- trauma/surgery within the last 3 months
- pregnancy or a bedridden state
- use of: heparin, vitamin K antagonists, antiplatelet drugs, contraceptives or hormone replacement therapy
About this study
Official title: High-dose Intravenous Methylprednisolone Therapy in Patients With Graves' Orbitopathy is Associated With the Increased Activity of Factor VIII
The alterations of coagulation and fibrinolysis parameters have been described in patients with endogenous Cushing's syndrome (CS) and those treated with glucocorticosteroids (GCs). The change in hemostatic process is associated with an increased risk of venous thromboembolic events (VTE) and pulmonary embolism (PE). Anticoagulation prophylaxis reduces thromboembolic complications in endogenous and exogenous hypercortisolism. The impact of the intravenous GCs therapy on hypercoagulability, however, remains unclear and perplexing. 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.: PE, 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. Nevertheless, even smaller cumulative therapy may be associated with fatal cardiovascular complications. Hence the aim of our study was to evaluate the effects of IVMP therapy on hemostatic process in patients with GO. All of patients were treated according to EUGOGO recommendations with standard doses of methylprednisolone with standard recommended schedule. Inclusion criterion for the therapy was according to EUGOGO guidelines moderate-to-severe and active GO (12 pulses of IVMP 6x0.5g followed by 6x0.25g every week).
Read the detailed description
The end point of the study was a change in hemostatic variables' levels in laboratory tests. There were short- and long-term hemostatic changes analysed during IVMP therapy: comparisons of laboratory tests before, 24h and 48h after selected pulses, and between the beginning of 1st, 6th and 12th IVMP pulses, respectively. Hemostatic variables that were evaluated: factor [F] II, FV, FVII, FVIII, fibrinogen, antithrombin, activated partial thromboplastin time, prothrombin time, platelets and D - dimer. Moreover, analyses were performed concerning clinical data (such as age, sex, body mass index, smoking, duration time of GO, presence of hypertension, basal markers of thyroid function) between independent groups (patients with initially increased/reduced selected markers versus without increased/reduced selected markers).
- Being tested
- Methylprednisolone
- Keywords
- Graves' Disease, Graves Ophthalmopathy, Blood Coagulation, Venous Thromboembolism, Methylprednisolone
- Medical subject headings
- Graves Disease, Graves Ophthalmopathy, Thrombosis, Venous Thromboembolism
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.
Change in activity of coagulation factor VIII from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Measured: 24 hours
Change in activity of coagulation factor VIII from baseline (before therapy) to the end of the course of therapy with methylprednisolone
Measured: 12 weeks
Change in of activated partial thromboplastin time (seconds) from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Measured: 24 hours
Change in activated partial thromboplastin time (seconds) from baseline (before therapy) to the end of the course of therapy with methylprednisolone
Measured: 12 weeks
Secondary outcomes (14)
Change in activity of coagulation factor II from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Measured: 24 hours
Change in activity of coagulation factor V from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Measured: 24 hours
Change in activity of coagulation factor VII from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Measured: 24 hours
Change in prothrombin time (seconds) from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Measured: 24 hours
Change in fibrinogen (mg/dl) from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Measured: 24 hours
Change in D-Dimer (ng/dl) from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Measured: 24 hours
Change in PLT count from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Measured: 24 hours
Change in activity of coagulation factor II from baseline (before therapy) to the end of the course of therapy with methylprednisolone
Measured: 12 weeks
Change in activity of coagulation factor V from baseline (before therapy) to the end of the course of therapy with methylprednisolone
Measured: 12 weeks
Change in activity of coagulation factor VII from baseline (before therapy) to the end of the course of therapy with methylprednisolone
Measured: 12 weeks
Change in prothrombin time (seconds) from baseline (before therapy) to the end of the course of therapy with methylprednisolone
Measured: 12 weeks
Change in fibrinogen (mg/dl) from baseline (before therapy) to the end of the course of therapy with methylprednisolone
Measured: 12 weeks
Change in D-Dimer (ng/dl) from baseline (before therapy) to the end of the course of therapy with methylprednisolone
Measured: 12 weeks
Change in PLT count from baseline (before therapy) to the end of the course of therapy with methylprednisolone
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2018
- Study start1 Jan 2011
- Primary completion31 Dec 2014
- Study completion31 Dec 2014
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.
- 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
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Piotr Miskiewicz
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Piotr Miskiewicz, Medical University of Warsaw
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03535090
- Sponsor's protocol ID
- IVMPCoagulation
- Status last verified
- May 2018
- First submitted
- 29 Apr 2018
- Last updated
- 24 May 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: The collected data will be shared in a publication. It includes all laboratory results from all points of evaluation: hemostatic variables- factor \[F\] II, FV, FVII, FVIII, fibrinogen, activated partial thromboplastin time, prothrombin time, international normalized ratio of prothrombin time, platelet count and D - dimer.
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High-dose Intravenous Methylprednisolone Therapy in Patients With Graves' Orbitopathy is Associated With the Increased Activity of Factor VIII
- ClinicalTrials.gov ID
- NCT03535090
- Acronym / sponsor ID
- IVMPCoagulation
- Keywords
- Graves' Disease, Graves Ophthalmopathy, Blood Coagulation, Venous Thromboembolism, Methylprednisolone
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Piotr MiskiewiczUniversity, hospital or other
- Study start
- 1 Jan 2011 (actual)
- Primary completion
- 31 Dec 2014 (actual)
- Study completion
- 31 Dec 2014 (actual)
- First posted
- 24 May 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.
The alterations of coagulation and fibrinolysis parameters have been described in patients with endogenous Cushing's syndrome (CS) and those treated with glucocorticosteroids (GCs). The change in hemostatic process is associated with an increased risk of venous thromboembolic events (VTE) and pulmonary embolism (PE). Anticoagulation prophylaxis reduces thromboembolic complications in endogenous and exogenous hypercortisolism. The impact of the intravenous GCs therapy on hypercoagulability, however, remains unclear and perplexing. 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.: PE, 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. Nevertheless, even smaller cumulative therapy may be associated with fatal cardiovascular complications. Hence the aim of our study was to evaluate the effects of IVMP therapy on hemostatic process in patients with GO. All of patients were treated according to EUGOGO recommendations with standard doses of methylprednisolone with standard recommended schedule. Inclusion criterion for the therapy was according to EUGOGO guidelines moderate-to-severe and active GO (12 pulses of IVMP 6x0.5g followed by 6x0.25g every week).
Detailed description
The end point of the study was a change in hemostatic variables' levels in laboratory tests. There were short- and long-term hemostatic changes analysed during IVMP therapy: comparisons of laboratory tests before, 24h and 48h after selected pulses, and between the beginning of 1st, 6th and 12th IVMP pulses, respectively. Hemostatic variables that were evaluated: factor [F] II, FV, FVII, FVIII, fibrinogen, antithrombin, activated partial thromboplastin time, prothrombin time, platelets and D - dimer. Moreover, analyses were performed concerning clinical data (such as age, sex, body mass index, smoking, duration time of GO, presence of hypertension, basal markers of thyroid function) between independent groups (patients with initially increased/reduced selected markers versus without increased/reduced selected markers).
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
- Age groups
- Adult, Older adult
- Study population
- Patients admitted to the Endocrine Department
Key inclusion criteria (3 listed)
- active, moderate-to-severe Graves' orbitopathy according to EUGOGO classification
- euthyroidism for at least 1 month
- completion of at least first six IVMP pulses
Key exclusion criteria (11 listed)
- medical history of thromboembolic events
- cardiovascular morbidity (chronic heart failure, cardiovascular heart disease)
- uncontrolled hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg)
- liver disease (>3x increase of alanine aminotransferase and/or aspartate aminotransferase)
- active inflammation
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
Change in activity of coagulation factor VIII from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Time frame: 24 hours
Change in activity of coagulation factor VIII from baseline (before therapy) to the end of the course of therapy with methylprednisolone
Time frame: 12 weeks
Change in of activated partial thromboplastin time (seconds) from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Time frame: 24 hours
Change in activated partial thromboplastin time (seconds) from baseline (before therapy) to the end of the course of therapy with methylprednisolone
Time frame: 12 weeks
14 secondary outcomes
Change in activity of coagulation factor II from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Time frame: 24 hours
Change in activity of coagulation factor V from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Time frame: 24 hours
Change in activity of coagulation factor VII from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Time frame: 24 hours
Change in prothrombin time (seconds) from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Time frame: 24 hours
Change in fibrinogen (mg/dl) from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Time frame: 24 hours
Change in D-Dimer (ng/dl) from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Time frame: 24 hours
Change in PLT count from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Time frame: 24 hours
Change in activity of coagulation factor II from baseline (before therapy) to the end of the course of therapy with methylprednisolone
Time frame: 12 weeks
Change in activity of coagulation factor V from baseline (before therapy) to the end of the course of therapy with methylprednisolone
Time frame: 12 weeks
Change in activity of coagulation factor VII from baseline (before therapy) to the end of the course of therapy with methylprednisolone
Time frame: 12 weeks
Change in prothrombin time (seconds) from baseline (before therapy) to the end of the course of therapy with methylprednisolone
Time frame: 12 weeks
Change in fibrinogen (mg/dl) from baseline (before therapy) to the end of the course of therapy with methylprednisolone
Time frame: 12 weeks
Change in D-Dimer (ng/dl) from baseline (before therapy) to the end of the course of therapy with methylprednisolone
Time frame: 12 weeks
Change in PLT count from baseline (before therapy) to the end of the course of therapy with methylprednisolone
Time frame: 12 weeks
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 24 May 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: hemostatic variables- factor [F] II, FV, FVII, FVIII, fibrinogen, activated partial thromboplastin time, prothrombin time, international normalized ratio of prothrombin time, platelet count and D - dimer.
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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 Piotr Miskiewicz.
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 11 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 24 May 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?
Change in activity of coagulation factor VIII from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse (time frame: 24 hours). The study lists 4 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 24 May 2018.