Coagulation After Intravenous Methylprednisolone Administration

NCT ID: NCT03535090

Last Updated: 2018-05-24

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 26 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-01-01
• Study Completion Date: 2014-12-31

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).

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).

Conditions

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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).

Methylprednisolone

Intervention Type: DRUG

Interventions

Methylprednisolone

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Piotr Miskiewicz

OTHER

Sponsor Role: lead

Responsible Party

Piotr Miskiewicz

MD, PhD

Responsibility Role: SPONSOR_INVESTIGATOR

Other Identifiers

IVMPCoagulation

Identifier Type: -

Identifier Source: org_study_id