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Trial record 7 of 24 for:    "Hyperthyroidism" | "Anti-Inflammatory Agents"

Coagulation After Intravenous Methylprednisolone Administration

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ClinicalTrials.gov Identifier: NCT03535090
Recruitment Status : Completed
First Posted : May 24, 2018
Last Update Posted : May 24, 2018
Sponsor:
Information provided by (Responsible Party):
Piotr Miskiewicz, Medical University of Warsaw

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).

Condition or disease Intervention/treatment
Graves' Disease Graves Ophthalmopathy Blood Coagulation Venous Thromboembolism Drug: Methylprednisolone

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).

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Study Type : Observational
Actual Enrollment : 26 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: High-dose Intravenous Methylprednisolone Therapy in Patients With Graves' Orbitopathy is Associated With the Increased Activity of Factor VIII
Actual Study Start Date : January 1, 2011
Actual Primary Completion Date : December 31, 2014
Actual Study Completion Date : December 31, 2014


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).
Drug: Methylprednisolone



Primary Outcome Measures :
  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 Outcome Measures :
  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 Outcome Measures:
  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 ]

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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Probability Sample
Study Population
Patients admitted to the Endocrine Department
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

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Responsible Party: Piotr Miskiewicz, MD, PhD, Medical University of Warsaw
ClinicalTrials.gov Identifier: NCT03535090     History of Changes
Other Study ID Numbers: IVMPCoagulation
First Posted: May 24, 2018    Key Record Dates
Last Update Posted: May 24, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: The results of the study will be published in 2018
Keywords provided by Piotr Miskiewicz, Medical University of Warsaw:
Graves' Disease
Graves Ophthalmopathy
Blood Coagulation
Venous Thromboembolism
Methylprednisolone
Additional relevant MeSH terms:
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Hyperthyroidism
Anti-Inflammatory Agents
Graves Disease
Graves Ophthalmopathy
Thromboembolism
Venous Thromboembolism
Eye Diseases
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Exophthalmos
Orbital Diseases
Goiter
Thyroid Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Eye Diseases, Hereditary
Genetic Diseases, Inborn
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs