Impact of Intravenous Methylprednisolone Treatment on Blood Pressure

Blood Pressure Profile and NT-proBNP Dynamics in Response to Intravenous Methylprednisolone Pulse Therapy of Severe Graves' Orbitopathy

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).

Study Overview

• Status: Completed
• Conditions: Heart Failure; Hypertension; Graves Ophthalmopathy; Graves Disease; Blood Pressure
• Intervention / Treatment: 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.

• Study Type: Observational
• Enrollment (Actual): 32

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients admitted to the clinic for routine treatment of active, moderate-to-severe GO

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NT-proBNP 1-24h	Change in value of NT-proBNP from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse	24 hours
NT-proBNP 1-12w	Change in value of NT-proBNP from baseline (before administration of methylprednisolone) to the basic NT-proBNP before last pulse with methylprednisolone	12 weeks
48-hour ambulatory blood pressure monitoring (ABPM)- 1 mean BP	Analysis of changes in mean blood pressure in ABPM between day before methylprednisolone administration and second day after first pulse of methylprednisolone administration	48 hours
48-hour ambulatory blood pressure monitoring (ABPM)- 12 mean BP	Analysis of changes in mean blood pressure in ABPM between day before methylprednisolone administration and second day after 12th pulse of methylprednisolone administration	12 weeks
48-hour ambulatory blood pressure monitoring (ABPM)- 1 max systolic BP	Analysis of changes in maximal systolic blood pressure in ABPM between day before methylprednisolone administration and second day after first pulse of methylprednisolone administration	48 hours
48-hour ambulatory blood pressure monitoring (ABPM)- 12 max systolic BP	Analysis of changes in maximal systolic blood pressure in ABPM between day before methylprednisolone administration and second day after 12th pulse of methylprednisolone administration	48 hours
echocardiographic examinations - median values of Ejection Fraction (EF)	Analysis of change in median values of EF between echocardiographic examinations before first methylprednisolone administration and after last pulse of methylprednisolone	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hs-CRP	Change in value of hs-CRP from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse	24 hours
Biomarker of cardiomyocyte injury - TnI	Change in value of TnI from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse	24 hours
NT-proBNP 1-48h	Change in value of NT-proBNP from baseline (before administration of methylprednisolone) to 48 hours after first intravenous pulse	48 hours

Collaborators and Investigators

• Sponsor: Medical University of Warsaw

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2011
• Primary Completion (ACTUAL): December 30, 2015
• Study Completion (ACTUAL): December 30, 2015

Study Registration Dates

• First Submitted: June 30, 2018
• First Submitted That Met QC Criteria: July 17, 2018
• First Posted (ACTUAL): July 18, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 18, 2018
• Last Update Submitted That Met QC Criteria: July 17, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Graves' Ophthalmopathy; Hypertension; Blood Pressure; Glucocorticoids; Methylprednisolone; Graves' Disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Genetic Diseases, Inborn; Thyroid Diseases; Eye Diseases, Hereditary; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Hypertension; Eye Diseases; Graves Ophthalmopathy; Graves Disease; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: IVMPHeart

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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
• IPD Sharing Time Frame: The results of the study will be published in 2018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No