- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03535090
Coagulation After Intravenous Methylprednisolone Administration
May 12, 2018 updated by: Piotr Miskiewicz
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).
Study Overview
Status
Completed
Intervention / Treatment
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 Type
Observational
Enrollment (Actual)
26
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
N/A
Genders Eligible for Study
All
Sampling Method
Probability Sample
Study Population
Patients admitted to the Endocrine Department
Description
Inclusion Criteria:
- active, moderate-to-severe Graves' orbitopathy according to EUGOGO classification
- euthyroidism for at least 1 month
- completion of at least first six IVMP pulses
Exclusion Criteria:
- 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
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
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).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in activity of coagulation factor VIII from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Time Frame: 24 hours
|
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
|
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
|
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
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in activity of coagulation factor II from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Time Frame: 24 hours
|
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
|
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
|
24 hours
|
Change in prothrombin time (seconds) from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Time Frame: 24 hours
|
24 hours
|
Change in fibrinogen (mg/dl) from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Time Frame: 24 hours
|
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
|
24 hours
|
Change in PLT count from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse
Time Frame: 24 hours
|
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
|
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
|
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
|
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
|
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
|
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
|
12 weeks
|
Change in PLT count from baseline (before therapy) to the end of the course of therapy with methylprednisolone
Time Frame: 12 weeks
|
12 weeks
|
Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in activity of coagulation factor VIII from baseline (before administration of methylprednisolone) to 48 hours after the first intravenous pulse
Time Frame: 48 hours
|
48 hours
|
Change of activated partial thromboplastin time (seconds) from baseline (before administration of methylprednisolone) to 48 hours after the first intravenous pulse
Time Frame: 48 hours
|
48 hours
|
Change in activity of coagulation factor VIII from baseline (before therapy) to the sixth pulse of the methylprednisolone
Time Frame: 6 weeks
|
6 weeks
|
Change activated partial thromboplastin time (seconds) from baseline (before therapy) to the sixth pulse of the methylprednisolone
Time Frame: 6 weeks
|
6 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
January 1, 2011
Primary Completion (ACTUAL)
December 31, 2014
Study Completion (ACTUAL)
December 31, 2014
Study Registration Dates
First Submitted
April 29, 2018
First Submitted That Met QC Criteria
May 12, 2018
First Posted (ACTUAL)
May 24, 2018
Study Record Updates
Last Update Posted (ACTUAL)
May 24, 2018
Last Update Submitted That Met QC Criteria
May 12, 2018
Last Verified
May 1, 2018
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Autoimmune Diseases
- Endocrine System Diseases
- Genetic Diseases, Inborn
- Thyroid Diseases
- Embolism and Thrombosis
- Eye Diseases, Hereditary
- Exophthalmos
- Orbital Diseases
- Goiter
- Hyperthyroidism
- Eye Diseases
- Graves Ophthalmopathy
- Thromboembolism
- Venous Thromboembolism
- Graves Disease
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Neuroprotective Agents
- Protective Agents
- Prednisolone
- Methylprednisolone Acetate
- Methylprednisolone
- Methylprednisolone Hemisuccinate
- Prednisolone acetate
- Prednisolone hemisuccinate
- Prednisolone phosphate
Other Study ID Numbers
- IVMPCoagulation
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
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.
IPD Sharing Time Frame
The results of the study will be published in 2018
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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