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NCT Number: NCT03535090

Coagulation After Intravenous Methylprednisolone Administration

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).

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Key information

Conditions

Graves' Disease Autoimmune Diseases Blood Coagulation Cardiovascular Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Embolism and Thrombosis Endocrine System Diseases Exophthalmos Eye Diseases Eye Diseases, Hereditary Genetic Diseases, Inborn Goiter Graves Disease Graves Ophthalmopathy Hyperthyroidism Immune System Diseases Orbital Diseases Thromboembolism Thrombosis Thyroid Diseases Vascular Diseases Venous Thromboembolism

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

About this study

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).

Who can participate

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

methylprednisolone

Drug

Primary outcomes

  1. Change in activity of coagulation factor VIII from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse

    Time frame: 24 hours

  2. 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

  3. 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

  4. 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

Secondary outcomes

  1. Change in activity of coagulation factor II from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse

    Time frame: 24 hours

  2. Change in activity of coagulation factor V from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse

    Time frame: 24 hours

  3. Change in activity of coagulation factor VII from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse

    Time frame: 24 hours

  4. Change in prothrombin time (seconds) from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse

    Time frame: 24 hours

  5. Change in fibrinogen (mg/dl) from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse

    Time frame: 24 hours

  6. Change in D-Dimer (ng/dl) from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse

    Time frame: 24 hours

  7. Change in PLT count from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse

    Time frame: 24 hours

  8. 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

  9. 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

  10. 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

  11. Change in prothrombin time (seconds) from baseline (before therapy) to the end of the course of therapy with methylprednisolone

    Time frame: 12 weeks

  12. Change in fibrinogen (mg/dl) from baseline (before therapy) to the end of the course of therapy with methylprednisolone

    Time frame: 12 weeks

  13. Change in D-Dimer (ng/dl) from baseline (before therapy) to the end of the course of therapy with methylprednisolone

    Time frame: 12 weeks

  14. Change in PLT count from baseline (before therapy) to the end of the course of therapy with methylprednisolone

    Time frame: 12 weeks

Other outcomes

  1. 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

  2. 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

  3. Change in activity of coagulation factor VIII from baseline (before therapy) to the sixth pulse of the methylprednisolone

    Time frame: 6 weeks

  4. Change activated partial thromboplastin time (seconds) from baseline (before therapy) to the sixth pulse of the methylprednisolone

    Time frame: 6 weeks

Sponsors and collaborators

Lead sponsor

Piotr Miskiewicz

Other

Registry information

Official study title

High-dose Intravenous Methylprednisolone Therapy in Patients With Graves' Orbitopathy is Associated With the Increased Activity of Factor VIII

Important dates

Study start
2011
Primary completion
2014
Study completion
2014
First posted
May 24, 2018
Registry last updated
May 24, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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