Impact of Intravenous Methylprednisolone Treatment on Blood Pressure

NCT03590080 | Completed

• 1 other identifier: IVMPHeart
• Study Type: observational
• Target: 32
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Graves Disease; Graves Ophthalmopathy; Hypertension; Blood Pressure; Heart Failure

Keywords

Graves' Disease; Graves' Ophthalmopathy; Hypertension; Blood Pressure; Methylprednisolone; Glucocorticoids

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (3)

• hs-CRP

  24 hours

• Biomarker of cardiomyocyte injury - TnI

  24 hours

• NT-proBNP 1-48h

  48 hours

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
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical University of Warsaw: lead

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).

MeSH Terms

Conditions

Graves Disease; Graves Ophthalmopathy; Hypertension; Heart Failure

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; Vascular Diseases; Cardiovascular Diseases; Heart Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Piotr Miśkiewicz, MD, PhD

  Department of Endocrinology Medical University of Warsaw

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 30, 2018
• First Posted: July 18, 2018
• Study Start: January 1, 2011
• Primary Completion: December 30, 2015
• Study Completion: December 30, 2015
• Last Updated: July 18, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: The results of the study will be published in 2018