Clinical trial NCT03590080: Impact of Intravenous Methylprednisolone Treatment on Blood Pressure
Official title: Blood Pressure Profile and NT-proBNP Dynamics in Response to Intravenous Methylprednisolone Pulse Therapy of Severe Graves' Orbitopathy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Graves Disease
Graves Ophthalmopathy
Hypertension
Blood Pressure
Heart Failure
Keywords: Graves' Disease
Graves' Ophthalmopathy
Hypertension
Blood Pressure
Methylprednisolone
Glucocorticoids
Lead sponsor: Medical University of Warsaw
Sponsor class: OTHER
First posted: 2018-07-18
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients admitted to the clinic for routine treatment of active, moderate-to-severe GO

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).

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.

Eligibility 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.

Primary outcomes:
measure: NT-proBNP 1-24h
timeFrame: 24 hours
measure: NT-proBNP 1-12w
timeFrame: 12 weeks
measure: 48-hour ambulatory blood pressure monitoring (ABPM)- 1 mean BP
timeFrame: 48 hours
measure: 48-hour ambulatory blood pressure monitoring (ABPM)- 12 mean BP
timeFrame: 12 weeks
measure: 48-hour ambulatory blood pressure monitoring (ABPM)- 1 max systolic BP
timeFrame: 48 hours
measure: 48-hour ambulatory blood pressure monitoring (ABPM)- 12 max systolic BP
timeFrame: 48 hours
measure: echocardiographic examinations - median values of Ejection Fraction (EF)
timeFrame: 12 weeks
Secondary outcomes:
measure: hs-CRP
timeFrame: 24 hours
measure: Biomarker of cardiomyocyte injury - TnI
timeFrame: 24 hours
measure: NT-proBNP 1-48h
timeFrame: 48 hours
Other outcomes:
Locations:
Study officials:
affiliation: Department of Endocrinology Medical University of Warsaw
name: Piotr Miśkiewicz, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: