Taper Or Abrupt Steroid Stop: TOASSTtrial

Autoimmune Clinical Trial

— TOASST  

Official title:

Glucocorticoid Withdrawal and Glucocorticoid-induced Adrenal Insufficiency: a Randomized Controlled Multicenter Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03153527
• Other study ID #: 2016-00487; ex14Rutishauser
• Status: Recruiting
• Phase: Phase 4
• Start date: May 31, 2017
• Est. completion date: December 2024

Study information

• Verified date: November 2023
• Source: University Hospital, Basel, Switzerland
• Contact: Jonas Rutishauser, Prof MD
• Phone: +41-56-486 25 16
• Email: j.rutishauser[@]unibas.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 573
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Autoimmune
• Inflammatory Disorder

Intervention

Drug:
• Prednisone
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.

Other:
• Placebo Arm
The experimental intervention consists of stopping glucocorticoid treatment abruptly and administering matching placebo over 4 weeks.

Locations

Country	Name	City	State
Germany	University Hospital Frankfurt	Frankfurt
Germany	University Hospital Würzburg	Würzburg
Switzerland	Departement of Internal Medicine, Kantonsspital Aarau	Aarau
Switzerland	Kantonsspital Baden	Baden
Switzerland	Endocrinology/Diabetology/Metabolism; University Hospital Basel	Basel
Switzerland	Department of Rheumatology, Immunology, and Allergology, Inselspital	Bern
Switzerland	Division of Gastroenterology, Spital Bülach AG	Bülach
Switzerland	Kantonsspital Frauenfeld	Frauenfeld
Switzerland	Geneva University Hospitals	Geneva
Switzerland	Center for Primary Health Care,University of Basel, Kantonsspital Baselland	Liestal
Switzerland	Internal Medicine, Kantonsspital Baselland/Liestal	Liestal
Switzerland	Department of Internal Medicine, Kantonsspital Münsterlingen	Münsterlingen
Switzerland	Stoffwechselzentrum, Kantonsspital Olten	Olten
Switzerland	Department of Internal Medicine, Kantonsspital St. Gallen	St. Gallen
Switzerland	Dept. of Endocrinology, Diabetology and Clinical Nutrition, University Hospital	Zürich

Sponsors (4)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	HEMMI Stiftung Switzerland, Kantonsspital Baselland Bruderholz, Swiss National Science Foundation

Countries where clinical trial is conducted

Germany,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	up to 6 months
Secondary	Time to specific incidence	Time to first occurrence of individual components of the primary outcome;	up to 6 months
Secondary	Cumulative overall systemic glucocorticoid dose	Cumulative overall systemic glucocorticoid dose	up to 6 months
Secondary	Cumulative systemic glucocorticoid dose administered to treat or prevent adrenal failure	Cumulative systemic glucocorticoid dose administered to treat or prevent adrenal failure	up to 6 months
Secondary	Cumulative systemic glucocorticoid dose administered to treat relapse	Cumulative systemic glucocorticoid dose administered to treat relapse of disease, specified for each disease	up to 6 months
Secondary	General health status	General health status as self-assessed by the participant on a visual analog scale (VAS) from 0 to 100	assessed at days 1, 7, 28, 35, 90,180
Secondary	Score of symptoms and signs of hypocortisolism	Score of symptoms and signs of hypocortisolism: weakness, hypothermia, nausea, vomiting, abdominal pain, fatigue, dizziness, Blood pressure, serum Na and serum glucose concentrations.	up to 6 months
Secondary	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	up to 6 months
Secondary	In patients hospitalized at study entry: length of hospital stay	In patients hospitalized at study entry: length of hospital stay	up to 6 months