Coagulation After Intravenous Methylprednisolone Administration

NCT03535090 | Completed

• 1 other identifier: IVMPCoagulation
• Study Type: observational
• Target: 26
• Locations: 0 countries
• Sites: N/A

Brief 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). 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).

Conditions

Graves' Disease; Graves Ophthalmopathy; Blood Coagulation; Venous Thromboembolism

Keywords

Graves' Disease; Graves Ophthalmopathy; Blood Coagulation; Venous Thromboembolism; Methylprednisolone

Outcome Measures

Primary Outcomes (4)

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

  24 hours

• Change in activity of coagulation factor VIII from baseline (before therapy) to the end of the course of therapy with methylprednisolone

  12 weeks

• Change in of activated partial thromboplastin time (seconds) from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse

  24 hours

• Change in activated partial thromboplastin time (seconds) from baseline (before therapy) to the end of the course of therapy with methylprednisolone

  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

  24 hours

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

  24 hours

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

  24 hours

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

  24 hours

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

  24 hours

Other Outcomes (4)

• Change in activity of coagulation factor VIII from baseline (before administration of methylprednisolone) to 48 hours after the first intravenous pulse

  48 hours

• Change of activated partial thromboplastin time (seconds) from baseline (before administration of methylprednisolone) to 48 hours after the first intravenous pulse

  48 hours

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

  6 weeks

Study Arms (1)

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).

Drug: Methylprednisolone

Interventions

Methylprednisolone DRUG

active, moderate-to-severe GO

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients admitted to the Endocrine Department

You may qualify if:

• active, moderate-to-severe Graves' orbitopathy according to EUGOGO classification
• euthyroidism for at least 1 month
• completion of at least first six IVMP pulses

You may not qualify if:

• 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

Sponsors & Collaborators

• Piotr Miskiewicz: lead

Biospecimen

Retention: SAMPLES WITHOUT DNA

Venous blood was collected in the morning following a 12 hour fast. This was utilized for preparation of serum, 3.2% sodium citrate plasma, and citrate platelet - poor plasma after double centrifugation. Hemostatic parameters were analyzed within 1 - 1.5 hour after blood sampling, except for FVIII activity measured in platelet - poor plasma stored frozen at -70°C until assay.

MeSH Terms

Conditions

Graves Disease; Graves Ophthalmopathy; Thrombosis; Venous Thromboembolism

Interventions

Methylprednisolone

Condition Hierarchy (Ancestors)

Exophthalmos; Orbital Diseases; Eye Diseases; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases; Eye Diseases, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Thromboembolism

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: April 29, 2018
• First Posted: May 24, 2018
• Study Start: January 1, 2011
• Primary Completion: December 31, 2014
• Study Completion: December 31, 2014
• Last Updated: May 24, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The results of the study will be published in 2018