RESCUE - Effect of Supplemental Hydrocortisone During Stress in Prednisolone-induced Adrenal Insufficiency; A Multicentre, Randomised, Double Blinded, Placebo-controlled Clinical Trial on Health-related Quality of Life in Patients With Polymyalgia Rheumatica/Giant Cell Arteritis Receiving Ongoing Low-dose Prednisolone Treatment.
概览
- 阶段
- 4 期
- 干预措施
- Hydrocortisone
- 疾病 / 适应症
- Adrenal Insufficiency
- 发起方
- Marianne Christina Klose
- 入组人数
- 250
- 试验地点
- 3
- 主要终点
- ecological momentary assessments (EMA) of the Multidimensional Fatigue Inventory (MFI-20) General Fatigue scale, adjusted for EMA
- 状态
- 招募中
- 最后更新
- 上个月
概览
简要总结
In this double-blinded randomised placebo-controlled clinical trial, the aim is to determine the effect of supplemental hydrocortisone compared with placebo during mild to moderate physical or mental stress on health related quality of life in patients with polymyalgia rheumatica (PMR)/giant cell arteritis (GCA) on ongoing low-dose prednisolone diagnosed with glucocorticoid-induced adrenal insufficiency. The main emphasis is on fatigue (primary outcome) and daily variation hereof during periods of stress.
详细描述
The study will include patients with PMR/GCA on ongoing prednisolone treatment in a low dose of \> 0 mg/day and ≤5mg/day. Eligible patients will undergo a Synacthen® test and 250 patients with a stimulated cortisol level \<420 nmol/l (biochemical adrenal insufficiency) will be randomised to either placebo or hydrocortisone supplemental doses during stress. Patients will continue prednisolone treatment and tapering hereof according to current clinical guidelines for PMR/GCA and add supplemental hydrocortisone/placebo in situations of stress according to study protocol. In situations of severe stress (potential adrenal crisis) patients will receive open label hydrocortisone treatment according to routine clinical care. The duration of RESCUE is 6 months but stops earlier if the patient stops prednisolone treatment earlier. In case of a flare of PMR/GCA during the study where prednisolone is increased to \>5mg/day for e.g. 5 weeks the study is prolonged accordingly 5 weeks. Ninety-five patients with stimulated cortisol ≥420 nmol/l (normal adrenal function) will be used as a reference group. The participants will undergo screening and baseline examinations, 3 month's reporting of HRQoL, and with patient consent follow-up through medical records on prednisolone treatment characteristics, and number of hospitalisations.
研究者
Marianne Christina Klose
MD, PhD
Rigshospitalet, Denmark
入排标准
入选标准
- •Age ≥ 50 years
- •Women must be postmenopausal (FSH is measured at the screening visit)
- •A diagnosis of PMR/GCA, or both conditions combined.
- •Treatment with prednisolone ≥12 weeks
- •Ongoing prednisolone treatment, with current daily prednisolone dose \> 0 mg and ≤5 mg. The dose must have been ≤5 mg for minimum 2 weeks at the time of the screening visit.
排除标准
- •Known primary or secondary adrenal insufficiency
- •Known Cushing's Syndrome
- •Known allergy towards study medication ingredients
- •Severe comorbidity: Heart failure (New York Heart Association class IV); Kidney failure with an estimated glomerular filtration rate \<30 mL/min (Chronic kidney disease stage 4-5); Liver disease in the form of cirrhosis; Active cancer; Known severe immune deficiency; A history of psychiatric disease requiring treatment by a psychiatric department (for affective disorders only if within the last year before study entry)
- •Alcohol consumption \>21 units per week
- •Planned major surgery during the study period at study entry.
- •Use of drugs that interfere with cortisol metabolism/measurements: Systemic oestrogen treatment (discontinued \< 1 month before inclusion), Treatment with strong CYP3A4 inhibitors or inducers, Use of other glucocorticoid formulations (Inhaled corticosteroids, intraarticular or intramuscular injections, steroid creams European steroid group IV-V used in the genital area. Note: Permitted glucocorticoid formulations: Eye-drops, nasal spray, glucocorticoid creams European steroid group I-III, and European steroid group IV-V used in the non-genital area only.)
- •Inability to provide written informed consent.
研究组 & 干预措施
RCT group - hydrocortisone
Patients with polymyalgia rheumatica/giant cell arteritis with glucocorticoid-induced adrenal insufficiency (Synacthen test response \<420 nmol/l) that are randomised to receive hydrocortisone
干预措施: Hydrocortisone
RCT group - placebo
Patients with polymyalgia rheumatica/giant cell arteritis with glucocorticoid-induced adrenal insufficiency (Synacthen test response \<420 nmol/l) that are randomised to receive placebo
干预措施: Placebo for hydrocortisone
Control group
Patients with polymyalgia rheumatica/giant cell arteritis with normal adrenal function (Synacthen test response ≥420 nmol/l)
结局指标
主要结局
ecological momentary assessments (EMA) of the Multidimensional Fatigue Inventory (MFI-20) General Fatigue scale, adjusted for EMA
时间窗: In situations of stress, participants are asked to answer the EMA items 5 times daily at semi-randomised time points, for 3 days. Diurnal profiles are generated and one diurnal profile summarizes responses during the day across all 'sick-days'.
EMA in situations of stress. EMA reporting will be conducted electronically on a smartphone.
次要结局
- Body composition and muscle strength - Waist, hip, height(Baseline and 6 months)
- Metabolic and cardiovascular risk - Automated office blood pressure(Baseline and 6 months)
- Biological integrated cortisol status assessment - 24h urine(At baseline, (3 months) and 6 months)
- Incidens of adrenal crises and hospitalisations(Throughout study period (6 months))
- Biological integrated cortisol status assessment - P-cortisol after 24 hours prednisolone pause.(At baseline, (3 months) and 6 months)
- Daily 'end-of-day' app-facilitated patient reported outcome (PRO) assessments(Patients are asked daily throughout the study period as 'end-of-day' assessments.)
- Number of 'sick days'(Throughout study period (6 months))
- Body composition and muscle strength -weight(Baseline and 6 months)
- Body composition and muscle strength - Timed up and go(Baseline and 6 months)
- Body composition and muscle strength - Handgrip strength(Baseline and 6 months)
- SF-36(At baseline, 3 months and 6 months)
- Body composition and muscle strength - DXA scan(Baseline and 6 months)
- Bone quality - Dual-energy X-ray absorptiometry (DXA) scan(Baseline and 6 months)
- Metabolic and cardiovascular risk (Coagulation and Inflammation markers in blood)(Baseline and 6 months)
- Patient reported symptoms of hypercortisolism - Single item Sleep Quality Scale (SQS))(Baseline and 6 months)
- Biological integrated cortisol status assessment - ACTH test(At baseline, (3 months) and 6 months)
- Body composition and muscle strength - Short Physical Performance Battery(Baseline and 6 months)
- Biological integrated cortisol status assessment - Salivary cortisol/cortisone(At baseline, (3 months) and 6 months)
- Biological integrated cortisol status assessment - Circulating biomarkers of glucocorticoid effects and adverse effects(At baseline, (3 months) and 6 months)
- AddiQol-30(At baseline, 3 months and 6 months)
- PMR/GCA treatment characteristics -accumulated glucocorticoid dose(Information from 6 months before baseline to end-of study)
- PMR/GCA treatment characteristics -prednisolone treatment duration(Information from 6 months before baseline to end-of study)
- Adrenal crises grading(Throughout study period (6 months))
- Body composition and muscle strength - body mass index (BMI)(Baseline and 6 months)
- Metabolic and cardiovascular risk - Metabolic and cardiovascular markers in blood and urine(Baseline and 6 months)
- Body composition and muscle strength - Chair rising test(Baseline and 6 months)
- Bone quality - bone markers in blood and urine(Baseline and 6 months)
- Patient reported symptoms of hypercortisolism - CushingQol(Baseline and 6 months)
- ecological momentary assessments (EMA) of the Multidimensional Fatigue Inventory (MFI-20) General Fatigue scale, adjusted for EMA(EMA is used at fixed time points monthly. Participants are asked to answer the EMA items 5 times daily at semi-randomised time points, for 3 days. Diurnal profiles are generated and one diurnal profile summarizes responses during the day across all days.)
- Influence of the length of the prednisolone pause (0 vs. 1 vs. 2 days) on ACTH test outcome(The ACTH tests are performed at screening (1 day pause) and two extra ACTH tests in the following weeks, every second patient starting with the 2 days pause and every second with the 0 day pause.)
- Prednisolone cross reactivity in the Roche Elecsys cortisol II immunoassay(Blood samples are drawn at the screening, baseline and at the two extra ACTH test visits (0 and 2 days prednisolone pause))