This study is an Investigator-initiated, placebo-controlled, multicenter noninferiority trial, comparing rapid termination of systemic glucocorticoid treatment with a tapering regime over 4 weeks.
In total, 573 patients will be enrolled. Patients will be randomly assigned in a 1:1 ratio to either prednisone in decreasing doses over 4 weeks or placebo. Patients, treating physicians, and study personnel will be blinded to treatment allocation to either prednisone or matching placebo. At inclusion, we will perform a 250 micrograms Synacthen® stimulation test. The results of the test will be blinded to treating physicians and investigators, and its value to predict clinical outcome will only be assessed after completion of the trial. As a safety measure, all patients will be instructed about stress coverage as well as signs and symptoms of hypocortisolism and will be provided with emergency medication. Patients will be randomized to the standard (tapering) or the experimental (matching placebo) arm. Follow-up will be for six months. In order to improve adherence to the study and ensure feasibility, follow-up visits in most study centers will be by telephone only. Visits will be performed early after stopping glucocorticoids in both arms (i.e. at days 7 and 35) to ensure safety; the other two visits will be on days 90 and 180. Amendment approved in 1-2018: former exclusion criterion 'status post organ transplantation' was revised and deleted
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
573
The control intervention (standard treatment) consists of prednisone treatment in decreasing doses, starting with 7.5 mg q.d. and reducing the dose every 7 days, such that prednisone treatment is stopped after a total of 4 weeks.
The experimental intervention consists of stopping glucocorticoid treatment abruptly and administering matching placebo over 4 weeks.
University Hospital Frankfurt
Frankfurt, Germany
RECRUITINGUniversity Hospital Würzburg
Time to any incidence
Time to first occurrence of hospitalization, death, initiation of unplanned systemic glucocorticoid therapy, or adrenal crisis (defined as glucocorticoid-responsive hypotension or shock with or without accompanying symptoms and signs such as weakness, apathy, nausea, vomiting, abdominal pain, hypothermia, hyponatremia \[serum sodium \< 135 millimole (mM)\], hyperkalemia \[serum potassium \> 5 mM\], hypoglycemia \[plasma glucose \< 3.5 mM\]); whichever occurs first.
Time frame: up to 6 months
Time to specific incidence
Time to first occurrence of individual components of the primary outcome;
Time frame: up to 6 months
Cumulative overall systemic glucocorticoid dose
Cumulative overall systemic glucocorticoid dose
Time frame: up to 6 months
Cumulative systemic glucocorticoid dose administered to treat or prevent adrenal failure
Cumulative systemic glucocorticoid dose administered to treat or prevent adrenal failure
Time frame: up to 6 months
Cumulative systemic glucocorticoid dose administered to treat relapse
Cumulative systemic glucocorticoid dose administered to treat relapse of disease, specified for each disease
Time frame: up to 6 months
General health status
General health status as self-assessed by the participant on a visual analog scale (VAS) from 0 to 100
Time frame: assessed at days 1, 7, 28, 35, 90,180
Score of symptoms and signs of hypocortisolism
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Würzburg, Germany
Departement of Internal Medicine, Kantonsspital Aarau
Aarau, Switzerland
RECRUITINGKantonsspital Baden
Baden, Switzerland
RECRUITINGEndocrinology/Diabetology/Metabolism; University Hospital Basel
Basel, Switzerland
RECRUITINGDepartment of Rheumatology, Immunology, and Allergology, Inselspital
Bern, Switzerland
RECRUITINGDivision of Gastroenterology, Spital Bülach AG
Bülach, Switzerland
RECRUITINGKantonsspital Frauenfeld
Frauenfeld, Switzerland
RECRUITINGGeneva University Hospitals
Geneva, Switzerland
RECRUITINGCenter for Primary Health Care,University of Basel, Kantonsspital Baselland
Liestal, Switzerland
RECRUITING...and 5 more locations
Score of symptoms and signs of hypocortisolism: weakness, hypothermia, nausea, vomiting, abdominal pain, fatigue, dizziness, Blood pressure, serum Na and serum glucose concentrations.
Time frame: up to 6 months
Performance in 250 mcg Synacthen® test
Performance in 250 mcg Synacthen® test: test assessed day 1 in all participants, plus days 7 and 35 in those followed in centers Bruderholz, Luzern, Aarau
Time frame: up to 6 months
In patients hospitalized at study entry: length of hospital stay
In patients hospitalized at study entry: length of hospital stay
Time frame: up to 6 months