Hydrocortisone Versus Methylprednisolone for the Treatment of Glucocorticoid-Induced Adrenal Insufficiency
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Proportion of patients with recovery of the HPA axis.
研究概览
简要总结
This study aims to compare the use of methylprednisolone and hydrocortisone as replacement therapies in patients with glucocorticoid-induced adrenal insufficiency.
The primary goal is to evaluate and compare the recovery of the hypothalamic-pituitary-adrenal (HPA) axis.
详细描述
Glucocorticoids in supraphysiological doses are the most frequent cause of adrenal insufficiency due to the suppression of the hypothalamic-pituitary-adrenal (HPA) axis.
In cases of confirmed adrenal insufficiency, current guidelines recommend replacement therapy with physiological doses of short- and intermediate-acting glucocorticoids to prevent adrenal crises without inhibiting HPA axis recovery.
While hydrocortisone is the most commonly used short-acting glucocorticoid, methylprednisolone is widely prescribed in Slovenia.
Because methylprednisolone lacks mineralocorticoid effects, it appears to be a particularly suitable choice for patients with glucocorticoid-induced adrenal insufficiency, where mineralocorticoid secretion is not impaired.
This randomized, prospective, open-label interventional study will primarily evaluate non-inferiority regarding HPA axis recovery after 12 months, with a long-term assessment at 24 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age over 18 years.
- •Suspected adrenal insufficiency due to receiving supraphysiological doses of methylprednisolone for more than 4 weeks.
- •Receiving methylprednisolone 4 mg for at least the last 4 weeks.
- •Morning cortisol lower than 300 nmol/L.
- •Inadequate result of a short ACTH test performed on a physiological dose of methylprednisolone (cortisol rise after 30 min under 470 nmol/L AND after 60 min under 500 nmol/L).
- •No further indication for treating the underlying disease, and retreatment with glucocorticoids is not expected in the next 2 years.
- •Consent to participate in the research.
排除标准
- •Known organic disease of the pituitary-adrenal axis.
- •Body mass over 130 kg.
- •Advanced comorbidities.
- •Advanced heart failure (NYHA IV).
- •Chronic kidney disease IV, eGFR under 30 ml/min.
- •Liver cirrhosis.
- •Active malignant disease.
- •Immune deficiencies.
- •Planned major surgery during the study duration.
- •Receiving drugs affecting cortisol metabolism or interfering with cortisol measurements (e.g., systemic estrogens, strong inducers or inhibitors of CYP3A4).
- •Conditions affecting cortisol metabolism (pregnancy, liver disease, nephrotic syndrome).
- •Alcohol dependence syndrome (consuming more than 21 units of alcohol per week).
- •Shift (night) work.
- •Presence of comorbidities with an expected life expectancy of less than 3 years.
研究组 & 干预措施
patients with hydrocortisone
Patients will receive 15 mg of hydrocortisone daily. The dose is split into 10 mg in the morning after breakfast and 5 mg after 6-7 hours.
干预措施: Patients will receive 15 mg of hydrocortisone daily. The dose is split into 10 mg in the morning after breakfast and 5 mg after 6-7 hours. (Drug)
patients with metylprednisolone
Patients will receive 3 mg of methylprednisolone once daily. The dose is administered in the morning (1 ½ tablets of 2 mg methylprednisolone after breakfast).
干预措施: Patients will receive 3 mg of methylprednisolone once daily. The dose is administered in the morning (1 ½ tablets of 2 mg Medrol after breakfast). (Drug)
结局指标
主要结局
Proportion of patients with recovery of the HPA axis.
时间窗: 12 months
Replacement therapy for glucocorticoid-induced adrenal insufficiency with methylprednisolone in a physiologically equivalent morning dose is being evaluated for non-inferiority compared to hydrocortisone. Methylprednisolone is considered not inferior regarding the proportion of patients with HPA axis recovery after 12 months, provided the difference between the groups does not exceed the pre-specified non-inferiority margin of 10%. Recovery of the HPA axis is assessed via a short ACTH test, defined as a cortisol rise to at least 470 nmol/L after 30 minutes or at least 500 nmol/L after 60 minutes.
次要结局
- Secondary Analysis: Superiority of Methylprednisolone(12 months)
- Non-inferiority of Methylprednisolone at 24 Months(24 months)
- Number of adrenal crises.(24 months)
- Time required for HPA axis recovery based on the duration of previous glucocorticoid treatment.(up to 24 months)
- Predictive Value of Morning Serum Cortisol Concentration(Baseline, 3, 6, 12, 18, 24 months.)
- Predictive Value of Serum Dehydroepiandrosterone Sulfate (DHEA-S)(Baseline, 3 months, 6 months, 12 months, 18 months and 24 months)
- Predictive Value of Morning Salivary Cortisone(Baseline, 3 months, 6 months, 12 months, 18 months and 24 months)
- Change from Baseline in Glycated Hemoglobin (HbA1c)(Baseline, 3, 6, 12, 18, 24 months)
- Change from Baseline in Fasting Glucose(Baseline, 3, 6, 12, 18 and 24 months)
- Change from Baseline in Lipid Profile(Baseline, 3 months, 6 months, 12 months, 18 months, 24 months)
- Change from Baseline in Body Fat Percentage and Visceral Fat Mass(Baseline, 12 months and 24 months)
- Change from Baseline in Bone Mineral Density (BMD)(baseline, 12 and 24 months)
- Change from Baseline in Quality of Life Assessed by the 36-Item Short Form Health Survey (SF-36)(Time Frame: Baseline, 6, 12, 24 months.)
- Change from Baseline in Treatment Satisfaction Assessed by the Treatment Satisfaction Questionnaire for Medication (TSQM - 1.4)(3, 12 and 24 months)
研究者
Živa Dolenšek
MD
University Medical Centre Ljubljana