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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-002528-18 | EudraCT Number | ||
| H-21041930 | Other Identifier | The Committees of Health Research Ethics in the Capital Region of Denmark | |
| 2024-518272-30-00 | Other Identifier | CTIS |
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| Name | Class |
|---|---|
| Aarhus University Hospital | OTHER |
| Odense University Hospital | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RCT group - hydrocortisone | Active Comparator | Patients with polymyalgia rheumatica/giant cell arteritis with glucocorticoid-induced adrenal insufficiency (Synacthen test response <420 nmol/l) that are randomised to receive hydrocortisone |
|
| RCT group - placebo | Placebo Comparator | Patients with polymyalgia rheumatica/giant cell arteritis with glucocorticoid-induced adrenal insufficiency (Synacthen test response <420 nmol/l) that are randomised to receive placebo |
|
| Control group | No Intervention | Patients with polymyalgia rheumatica/giant cell arteritis with normal adrenal function (Synacthen test response ≥420 nmol/l) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hydrocortisone | Drug | Patients are randomised to either placebo or hydrocortisone supplemental doses in situations of stress. Patients will continue prednisolone treatment and tapering hereof according to current clinical guidelines for PMR/GCA , prednisolone is not part of the intervention. |
| Measure | Description | Time Frame |
|---|---|---|
| ecological momentary assessments (EMA) of the Multidimensional Fatigue Inventory (MFI-20) General Fatigue scale, adjusted for EMA | EMA in situations of stress. EMA reporting will be conducted electronically on a smartphone. | 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'. |
| Measure | Description | Time Frame |
|---|---|---|
| Daily 'end-of-day' app-facilitated patient reported outcome (PRO) assessments | Key secondary outcome - obtain information about intercurrent illness, injury, or stress, and symptoms of fatigue, nausea, and general malaise. The questions about symptoms originate from the Danish version of the PRO-CTCAE. | Patients are asked daily throughout the study period as 'end-of-day' assessments. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Marianne Klose, MD, PhD | Contact | +4530237532 | marianne.christina.klose.01@regionh.dk | |
| Stina W. Borresen, MD, PhD | Contact | +4525347551 | stina.borresen@regionh.dk |
| Name | Affiliation | Role |
|---|---|---|
| Ulla Feldt-Rasmussen, Professor | Rigshospitalet, Denmark | Principal Investigator |
| Marianne Klose, MD, PhD | Rigshospitalet, Denmark | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Endocrinology, Aarhus University Hospital | Recruiting | Aarhus | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42276802 | Derived | Borresen SW, Hansen SB, Al-Jorani H, Tei R, Dreyer AF, Boesen VB, Bislev LS, Jorgensen NT, Jensen RC, Bjergstrom MLL, Christensen LL, Frederiksen JSS, Glintborg D, Bjorner JB, Feldt-Rasmussen U, Jorgensen JOL, Andersen MS, Klose M. Effect of supplemental hydrocortisone during stress in prednisolone-induced adrenal insufficiency: a study protocol for a multicentre, randomised, double-blinded, placebo-controlled clinical trial on health-related quality of life in patients with polymyalgia rheumatica/giant cell arteritis on low-dose prednisolone treatment (the RESCUE study). BMJ Open. 2026 Jun 11;16(6):e113110. doi: 10.1136/bmjopen-2025-113110. |
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Deidentified patient data will be made available after completion of the study and publication of the main results, upon reasonable request. Data sharing will comply with GDPR and national data protection regulations.
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| ID | Term |
|---|---|
| D000309 | Adrenal Insufficiency |
| D011111 | Polymyalgia Rheumatica |
| D013700 | Giant Cell Arteritis |
| ID | Term |
|---|---|
| D000307 | Adrenal Gland Diseases |
| D004700 | Endocrine System Diseases |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
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| ID | Term |
|---|---|
| D006854 | Hydrocortisone |
| ID | Term |
|---|---|
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 |
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Double-blinded randomised placebo-controlled clinical trial
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Patients and all study personnel are blinded for study medication (hydrocortisone or placebo)
|
| Placebo for hydrocortisone | Drug | Patients are randomised to either placebo or hydrocortisone supplemental doses in situations of stress. Patients will continue prednisolone treatment and tapering hereof according to current clinical guidelines for PMR/GCA , prednisolone is not part of the intervention. |
|
| SF-36 | Key secondary outcome | At baseline, 3 months and 6 months |
| AddiQol-30 | Key secondary outcome | At baseline, 3 months and 6 months |
| PMR/GCA treatment characteristics -accumulated glucocorticoid dose | Key secondary outcome. accumulated glucocorticoid dose | Information from 6 months before baseline to end-of study |
| PMR/GCA treatment characteristics -prednisolone treatment duration | Key secondary outcome. Duration of prednisolone treatment, duration of prednisolone tapering (5 mg - 0 mg) | Information from 6 months before baseline to end-of study |
| Number of 'sick days' | Key secondary outcome | Throughout study period (6 months) |
| Incidens of adrenal crises and hospitalisations | Incidence rate of adrenal crises and hospitalisations | Throughout study period (6 months) |
| Adrenal crises grading | Grade of adrenal crises. | Throughout study period (6 months) |
| Body composition and muscle strength - DXA scan | Safety outcome for exogenous Cushing's Syndrome (Dual-energy X-ray absorptiometry (DXA) scan: fat percentage, body composition | Baseline and 6 months |
| Body composition and muscle strength - Waist, hip, height | Safety outcome for exogenous Cushing's Syndrome (Waist, hip, height) | Baseline and 6 months |
| Body composition and muscle strength -weight | Safety outcome for exogenous Cushing's Syndrome (weight) | Baseline and 6 months |
| Body composition and muscle strength - body mass index (BMI) | Safety outcome for exogenous Cushing's Syndrome (BMI) | Baseline and 6 months |
| Body composition and muscle strength - Timed up and go | Safety outcome for exogenous Cushing's Syndrome (Timed up and go) | Baseline and 6 months |
| Body composition and muscle strength - Handgrip strength | Safety outcome for exogenous Cushing's Syndrome (Handgrip strength) | Baseline and 6 months |
| Body composition and muscle strength - Short Physical Performance Battery | Safety outcome for exogenous Cushing's Syndrome (Short Physical Performance Battery) | Baseline and 6 months |
| Body composition and muscle strength - Chair rising test | Safety outcome for exogenous Cushing's Syndrome (Chair rising test) | Baseline and 6 months |
| Bone quality - Dual-energy X-ray absorptiometry (DXA) scan | Safety outcome for exogenous Cushing's Syndrome (DXA scan, vertebral and hip) | Baseline and 6 months |
| Bone quality - bone markers in blood and urine | Safety outcome for exogenous Cushing's Syndrome (bone markers in blood and urine) | Baseline and 6 months |
| Metabolic and cardiovascular risk - Automated office blood pressure | Safety outcome for exogenous Cushing's Syndrome (Automated office blood pressure) | Baseline and 6 months |
| Metabolic and cardiovascular risk (Coagulation and Inflammation markers in blood) | Safety outcome for exogenous Cushing's Syndrome (Coagulation and Inflammation markers in blood) | Baseline and 6 months |
| Metabolic and cardiovascular risk - Metabolic and cardiovascular markers in blood and urine | Safety outcome for exogenous Cushing's Syndrome (Metabolic and cardiovascular markers in blood and urine) | Baseline and 6 months |
| Patient reported symptoms of hypercortisolism - CushingQol | Safety outcome for exogenous Cushing's Syndrome (CushingQol) | Baseline and 6 months |
| Patient reported symptoms of hypercortisolism - Single item Sleep Quality Scale (SQS)) | Safety outcome for exogenous Cushing's Syndrome (Single item Sleep Quality Scale (SQS)) | Baseline and 6 months |
| Biological integrated cortisol status assessment - ACTH test | ACTH test for normalization of adrenal function | At baseline, (3 months) and 6 months |
| Biological integrated cortisol status assessment - 24h urine | 24h urine for cortisol and metabolites. | At baseline, (3 months) and 6 months |
| Biological integrated cortisol status assessment - Salivary cortisol/cortisone | Salivary cortisol/cortisone | At baseline, (3 months) and 6 months |
| Biological integrated cortisol status assessment - Circulating biomarkers of glucocorticoid effects and adverse effects | Circulating biomarkers of glucocorticoid effects and adverse effects. | At baseline, (3 months) and 6 months |
| Biological integrated cortisol status assessment - P-cortisol after 24 hours prednisolone pause. | P-cortisol after 24 hours prednisolone pause. | At baseline, (3 months) and 6 months |
| ecological momentary assessments (EMA) of the Multidimensional Fatigue Inventory (MFI-20) General Fatigue scale, adjusted for EMA | EMA in situations without stress, key-secondary putcome: EMA reporting will be conducted electronically on a smartphone | 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 | Forty patients (all on 5 mg prednisolone/day) will undergo two extra ACTH tests after 0 and 2 days of prednisolone pause, meaning last prednisolone dose taken on the day of the test or 2 days before the test, respectively. The exact number of hours of prednisolone pause is registered for each visit. For these patients, samples for ACTH measurements are drawn at each ACTH test, before ACTH injection. | 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 | Prednisolone cross reactivity in the Roche Elecsys cortisol II immunoassay at different timepoints (hours) since last prednisolone dose is determined in fourty consecutive patients by measuring plasma prednisolone concentrations with LC-MS and cortisol concentrations with both LC-MS and Roche Elecsys cortisol II immunoassay. Blood samples will be collected at 2 and 4 hours plus 1 and 2 days after the last prednisolone dose. | Blood samples are drawn at the screening, baseline and at the two extra ACTH test visits (0 and 2 days prednisolone pause) |
| Department of Medical Endocrinology, Copenhagen University Hospital, Rigshospitalet | Recruiting | Copenhagen | 2100 | Denmark |
|
| Department of Endocrinology, Odense University Hospital | Recruiting | Odense | Denmark |
|
| D012216 | Rheumatic Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D020293 | Vasculitis, Central Nervous System |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D001167 | Arteritis |
| D014657 | Vasculitis |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D015062 | 11-Hydroxycorticosteroids |
| D006889 | Hydroxycorticosteroids |
| D000305 | Adrenal Cortex Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D015065 | 17-Hydroxycorticosteroids |