Clinical trial NCT03153527: Taper Or Abrupt Steroid Stop: TOASSTtrial
Official title: Glucocorticoid Withdrawal and Glucocorticoid-induced Adrenal Insufficiency: a Randomized Controlled Multicenter Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Inflammatory Disorder
Autoimmune
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Kantonsspital Baselland Bruderholz
name: Swiss National Science Foundation
name: HEMMI Stiftung Switzerland
First posted: 2017-05-15
Enrollment: 573
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Standard treatment arm: Prednisone, a synthetic glucocorticoid with intermediate duration of action (biological half-life 18-35 hrs). The detailed characteristics of the compound, marketed under several brand names, can be found at www.swissmedicinfo.ch: Prednison Streuli (Swissmedic registration number: 29349); Prednison Axapharm (Swissmedic registration number: 58761); Prednison Galepharm (Swissmedic registration number: 50821).

Interventional treatment arm: matching placebo.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Eligibility criteria: Inclusion Criteria:

* Informed Consent as documented by signature (Appendix Informed Consent Form)
* Age ≥ 18 years
* Daily glucocorticoid dose ≥ 7.5 mg prednisone-equivalent at the time of inclusion
* Therapy over ≥ 28 days, ≥ 7.5 mg average daily dose, with a cumulative glucocorticoid dose ≥ 420 mg prednisone-equivalent prior to inclusion
* Tapering not or no longer mandatory to treat underlying disease

Exclusion Criteria:

* Primary adrenal failure
* Treatment with systemic depot glucocorticoids (e.g. intramuscular, epidural)
* Incapability to administer glucocorticoid cover treatment in situations of stress
* Inability or unwillingness to provide informed consent
* Women who are pregnant or breast feeding,
* Intention to become pregnant during the course of the study,
* Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases.
* Known or suspected non-compliance
* Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
* Participation in another study with investigational drug within the 30 days preceding and during the present study,
* Previous enrolment into the current study,
* Enrolment of the investigator, his/her family members, employees and other dependent persons

Primary outcomes:
measure: Time to any incidence
timeFrame: up to 6 months
Secondary outcomes:
measure: Time to specific incidence
timeFrame: up to 6 months
measure: Cumulative overall systemic glucocorticoid dose
timeFrame: up to 6 months
measure: Cumulative systemic glucocorticoid dose administered to treat or prevent adrenal failure
timeFrame: up to 6 months
measure: Cumulative systemic glucocorticoid dose administered to treat relapse
timeFrame: up to 6 months
measure: General health status
timeFrame: assessed at days 1, 7, 28, 35, 90,180
measure: Score of symptoms and signs of hypocortisolism
timeFrame: up to 6 months
measure: Performance in 250 mcg Synacthen® test
timeFrame: up to 6 months
measure: In patients hospitalized at study entry: length of hospital stay
timeFrame: up to 6 months
Other outcomes:
Locations:
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt
city: Würzburg
country: Germany
facility: University Hospital Würzburg
city: Aarau
country: Switzerland
facility: Departement of Internal Medicine, Kantonsspital Aarau
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Basel
country: Switzerland
facility: Endocrinology/Diabetology/Metabolism; University Hospital Basel
city: Bern
country: Switzerland
facility: Department of Rheumatology, Immunology, and Allergology, Inselspital
city: Bülach
country: Switzerland
facility: Division of Gastroenterology, Spital Bülach AG
city: Frauenfeld
country: Switzerland
facility: Kantonsspital Frauenfeld
city: Geneva
country: Switzerland
facility: Geneva University Hospitals
city: Liestal
country: Switzerland
facility: Center for Primary Health Care,University of Basel, Kantonsspital Baselland
city: Liestal
country: Switzerland
facility: Internal Medicine, Kantonsspital Baselland/Liestal
city: Münsterlingen
country: Switzerland
facility: Department of Internal Medicine, Kantonsspital Münsterlingen
city: Olten
country: Switzerland
facility: Stoffwechselzentrum, Kantonsspital Olten
city: St. Gallen
country: Switzerland
facility: Department of Internal Medicine, Kantonsspital St. Gallen
city: Zürich
country: Switzerland
facility: Dept. of Endocrinology, Diabetology and Clinical Nutrition, University Hospital
Study officials:
affiliation: Departement Medizin, Kantonsspital Baden
name: Jonas Rutishauser, Prof MD
role: PRINCIPAL_INVESTIGATOR
References: