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Trial record 4 of 17 for:    "Hyperthyroidism" | "Neuroprotective Agents"

Impact of Intravenous Methylprednisolone Treatment on Blood Pressure

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ClinicalTrials.gov Identifier: NCT03590080
Recruitment Status : Completed
First Posted : July 18, 2018
Last Update Posted : July 18, 2018
Sponsor:
Information provided by (Responsible Party):
Piotr Miskiewicz, Medical University of Warsaw

Brief Summary:
Hypertension is common side effect of Cushing Syndrome (CS): in patients with endogenous CS and those treated with glucocorticosteroids (GCs). The impact of the intravenous GCs therapy on blood pressure (BP) remains unclear. 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.: pulmonary embolism, 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. A consensus on the monitoring of patients during and after IVMP pulse administration is not yet established. What is more, there is lack of paper regarding pattern of blood pressure at various time points during and after ivGCs administration. Thus, the investigators decided to evaluate acute changes of N-terminal pro-brain natriuretic peptide (NT-proBNP) as a marker of hemodynamic stress and to monitor BP before, during and after IVMP pulse administration. All of patients were treated routinely according to EUGOGO recommendations with standard doses of methylprednisolone with standard recommended schedule. Inclusion criterion for the therapy was according to EUGOGO guidelines active, 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 Hypertension Blood Pressure Heart Failure Drug: Methylprednisolone

Detailed Description:
Laboratory tests such as NT-proBNP, troponin I (TnI) and high - sensitivity C - reactive protein (hs-CRP) were performed before, 24 h and 48 h after IVMP during the following pulses: 1st, 6th and 12th. Patients underwent echocardiographic examination before 1st and after 12th pulse. 48-hours ambulatory blood pressure monitoring (ABPM) (for 24 hours before and 24 hours after IVMP) was done during the following pulses: 1st, 6th and 12th.

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Study Type : Observational
Actual Enrollment : 32 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Blood Pressure Profile and NT-proBNP Dynamics in Response to Intravenous Methylprednisolone Pulse Therapy of Severe Graves' Orbitopathy
Actual Study Start Date : January 1, 2011
Actual Primary Completion Date : December 30, 2015
Actual Study Completion Date : December 30, 2015


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. NT-proBNP 1-24h [ Time Frame: 24 hours ]
    Change in value of NT-proBNP from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse

  2. NT-proBNP 1-12w [ Time Frame: 12 weeks ]
    Change in value of NT-proBNP from baseline (before administration of methylprednisolone) to the basic NT-proBNP before last pulse with methylprednisolone

  3. 48-hour ambulatory blood pressure monitoring (ABPM)- 1 mean BP [ Time Frame: 48 hours ]
    Analysis of changes in mean blood pressure in ABPM between day before methylprednisolone administration and second day after first pulse of methylprednisolone administration

  4. 48-hour ambulatory blood pressure monitoring (ABPM)- 12 mean BP [ Time Frame: 12 weeks ]
    Analysis of changes in mean blood pressure in ABPM between day before methylprednisolone administration and second day after 12th pulse of methylprednisolone administration

  5. 48-hour ambulatory blood pressure monitoring (ABPM)- 1 max systolic BP [ Time Frame: 48 hours ]
    Analysis of changes in maximal systolic blood pressure in ABPM between day before methylprednisolone administration and second day after first pulse of methylprednisolone administration

  6. 48-hour ambulatory blood pressure monitoring (ABPM)- 12 max systolic BP [ Time Frame: 48 hours ]
    Analysis of changes in maximal systolic blood pressure in ABPM between day before methylprednisolone administration and second day after 12th pulse of methylprednisolone administration

  7. echocardiographic examinations - median values of Ejection Fraction (EF) [ Time Frame: 12 weeks ]
    Analysis of change in median values of EF between echocardiographic examinations before first methylprednisolone administration and after last pulse of methylprednisolone


Secondary Outcome Measures :
  1. hs-CRP [ Time Frame: 24 hours ]
    Change in value of hs-CRP from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse

  2. Biomarker of cardiomyocyte injury - TnI [ Time Frame: 24 hours ]
    Change in value of TnI from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse

  3. NT-proBNP 1-48h [ Time Frame: 48 hours ]
    Change in value of NT-proBNP from baseline (before administration of methylprednisolone) to 48 hours after first intravenous pulse


Biospecimen Retention:   Samples Without DNA
All assays were performed in sera obtained from venous blood samples and analysed immediately after blood sampling in The Central Laboratory in the hospital. NT-proBNP was measured using a Flex® Reagent Cartridge and Dimension®EXLTM integrated chemistry system with a LOCI® Module (Siemens HealthCare Diagnostics Ltd., Camberley, UK). The cutoff value of NT - proBNP typical for hemodynamic stress in the left ventricle was defined as ≥125 pg/ml. Measurements of TnI and hs-CRP were made. Analysis of TnI was performed on Siemens Dimension System (ExL LOCI TnI assay). TnI values ≥ 0.056 ng/mL as above the 99th percentile were reported as positive. Measurement of hs-CRP was performed in serum using an immunoturbidimetric method on Cobas 6000 Analyzer (Roche Diagnostics).


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients admitted to the clinic for routine treatment of active, moderate-to-severe GO
Criteria

Inclusion Criteria:

  • active, moderate-to-severe GO according to EUGOGO classification
  • euthyroidism
  • completion of at least first six IVMP pulses.

Exclusion Criteria:

  • cardiovascular morbidity (such as chronic heart failure and/or coronary heart disease)
  • uncontrolled hypertension (defined as systolic blood pressure (SBP) more than 140 mmHg and/or diastolic blood pressure (DBP) more than 90 mmHg)
  • contraindications to IVMP therapy
  • previous GCs treatment in the last 6 months.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03590080


Sponsors and Collaborators
Medical University of Warsaw
Investigators
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Principal Investigator: Piotr Miśkiewicz, MD, PhD Department of Endocrinology Medical University of Warsaw

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Responsible Party: Piotr Miskiewicz, MD, PhD, Medical University of Warsaw
ClinicalTrials.gov Identifier: NCT03590080     History of Changes
Other Study ID Numbers: IVMPHeart
First Posted: July 18, 2018    Key Record Dates
Last Update Posted: July 18, 2018
Last Verified: July 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, results of 48 - hour ABPM and echocardiographic measurements
Time Frame: The results of the study will be published in 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Piotr Miskiewicz, Medical University of Warsaw:
Graves' Disease
Graves' Ophthalmopathy
Hypertension
Blood Pressure
Methylprednisolone
Glucocorticoids
Additional relevant MeSH terms:
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Hyperthyroidism
Neuroprotective Agents
Graves Disease
Graves Ophthalmopathy
Hypertension
Eye Diseases
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
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents