Impact of Intravenous Methylprednisolone Treatment on Blood Pressure

• Sponsor: Medical University of Warsaw (Other)
• Overall Status: Completed
• CT.gov ID: NCT03590080
• Collaborator: (none)
• Enrollment: 32
• Actual Duration (Months): 59.9

Study Details

Study Description

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	Phase
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.

Study Design

• 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: Jan 1, 2011
• Actual Primary Completion Date: Dec 30, 2015
• Actual Study Completion Date: Dec 30, 2015

Arms and Interventions

Arm	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

Outcome Measures

Primary Outcome Measures

1. NT-proBNP 1-24h [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 [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 [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 [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 [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 [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) [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 [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 [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 [48 hours]

   Change in value of NT-proBNP from baseline (before administration of methylprednisolone) to 48 hours after first intravenous pulse

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Medical University of Warsaw

Investigators

• Principal Investigator: Piotr Miśkiewicz, MD, PhD, Department of Endocrinology Medical University of Warsaw

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Piotr Miskiewicz, MD, PhD, Medical University of Warsaw
• ClinicalTrials.gov Identifier: NCT03590080
• Other Study ID Numbers: IVMPHeart
• First Posted: Jul 18, 2018
• Last Update Posted: Jul 18, 2018
• Last Verified: Jul 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Piotr Miskiewicz, MD, PhD, Medical University of Warsaw: Graves' Disease; Graves' Ophthalmopathy; Hypertension; Blood Pressure; Methylprednisolone; Glucocorticoids
• Additional relevant MeSH terms: Graves Disease; Eye Diseases; Graves Ophthalmopathy; Hypertension; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

Study Results

No Results Posted as of Jul 18, 2018