Taper Or Abrupt Steroid Stop: TOASSTtrial (TOASST)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Autoimmune; Inflammatory Disorder
• Intervention / Treatment: Other: Placebo Arm; Drug: Prednisone

Detailed Description

In total, 530 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
• Enrollment (Estimated): 530
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jonas Rutishauser, Prof MD; Phone Number: +41-56-486 25 14; Email: j.rutishauser@unibas.ch

Study Locations

• Germany
  • Frankfurt, Germany
    • Recruiting
    • University Hospital Frankfurt
    • Contact: Jörg Bojunga, Prof. Dr. med.
    • Principal Investigator: Jörg Bojunga, Prof. Dr. med.
    • Sub-Investigator: Gesine Meyer, PD Dr. med.
  • Würzburg, Germany, 97080
    • Recruiting
    • University Hospital Wurzburg
    • Contact: Irina Chifu, Dr. med.
    • Contact: Martin Fassnacht, Prof Dr. med.; Phone Number: +49-931-201-39201; Email: Fassnacht_M@ukw.de
    • Sub-Investigator: Martin Fassnacht, Prof Dr. med.
    • Principal Investigator: Irina Chifu, Dr. med.
• Switzerland
  • Aarau, Switzerland, 5001
    • Recruiting
    • Departement of Internal Medicine, Kantonsspital Aarau
    • Contact: Philip Schuetz, Prof Dr med; Phone Number: +41 62 838 95 24; Email: schuetzph@gmail.com
  • Baden, Switzerland, 5404
    • Recruiting
    • Kantonsspital Baden
    • Contact: Jonas Rutishauser, Prof. Dr. MD; Phone Number: +41-56-486 25 14; Email: j.rutishauser@unibas.ch
  • Basel, Switzerland, 4031
    • Terminated
    • Endocrinology/Diabetology/Metabolism; University Hospital Basel
  • Basel, Switzerland, 4058
    • Recruiting
    • St. Claraspital Basel
    • Contact: Matthias Hepprich; Phone Number: +41 61 685 89 40; Email: matthias.hepprich@claraspital.ch
    • Principal Investigator: Matthias Hepprich
  • Bern, Switzerland, 3010
    • Terminated
    • Department of Rheumatology, Immunology, and Allergology, Inselspital
  • Bülach, Switzerland, 8180
    • Terminated
    • Division of Gastroenterology, Spital Bülach AG
  • Frauenfeld, Switzerland, 8501
    • Recruiting
    • Kantonsspital Frauenfeld
    • Contact: Andreas Kistler, PD Dr. med.; Phone Number: +41 52 723 76 43; Email: andreas.kistler@stgag.ch
    • Principal Investigator: Andreas Kistler, PD Dr. med.
  • Geneva, Switzerland, 1205
    • Recruiting
    • Geneva University Hospitals
    • Contact: Jean-Luc Reny, Prof. Dr. med.; Phone Number: +41 22 372 90 52
    • Principal Investigator: Jean-Luc Reny, Prof. Dr. med.
  • Liestal, Switzerland, 4410
    • Recruiting
    • Internal Medicine, Kantonsspital Baselland/Liestal
    • Contact: Jörg Leuppi, Prof Dr med; Phone Number: +41-61-925 21 80; Email: joerg.leuppi@ksbl.ch
  • Liestal, Switzerland, 4410
    • Terminated
    • Center for Primary Health Care,University of Basel, Kantonsspital Baselland
  • Münsterlingen, Switzerland, 8596
    • Recruiting
    • Department of Internal Medicine, Kantonsspital Münsterlingen
    • Contact: Robert Thurnheer; Phone Number: +41 71 686 21 75; Email: robert.thurnheer@stgag.ch
    • Principal Investigator: Robert Thurnheer, Prof. Dr. med
  • Olten, Switzerland, 4600
    • Terminated
    • Stoffwechselzentrum, Kantonsspital Olten
  • Sankt Gallen, Switzerland, 9007
    • Recruiting
    • Department of Internal Medicine, Kantonsspital St. Gallen
    • Contact: Michael Brändle, Prof Dr med; Phone Number: +41-71-494 61 21; Email: michael.braendle@kssg.ch
  • Zurich, Switzerland, 8091
    • Terminated
    • Dept. of Endocrinology, Diabetology and Clinical Nutrition, University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo arm (intervention arm); Stop glucocorticoid treatment; administer placebo matching the verum preparation in weekly intervals.	Other: Placebo Arm; The experimental intervention consists of stopping glucocorticoid treatment abruptly and administering matching placebo over 4 weeks.
Active Comparator: Verum group (control/standard arm); If patient is on > 7.5 mg prednisone-equivalent daily: administer 7.5 mg q.d. for 7 days, then 5 mg q.d. for 7 days, then 2.5 mg q.d. for 7 days, then 2.5 mg q.d. every second day, then stop. If patient on 7.5 mg q.d.: maintain for 7 days, then taper as above.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to specific incidence	Time to first occurrence of individual components of the primary outcome;	up to 6 months
Cumulative overall systemic glucocorticoid dose	Cumulative overall systemic glucocorticoid dose	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	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	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	assessed at days 1, 7, 28, 35, 90,180
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
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
In patients hospitalized at study entry: length of hospital stay	In patients hospitalized at study entry: length of hospital stay	up to 6 months

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: Swiss National Science Foundation; Kantonsspital Baselland Bruderholz; HEMMI Stiftung Switzerland; Gebauer Stiftung Zurich
• Investigators: Principal Investigator: Jonas Rutishauser, Prof MD, Departement Medizin, Kantonsspital Baden

Publications and helpful links

General Publications

• Komminoth M, Donath MY, Hepprich M, Schuetz P, Blum CA, Mueller B, Reny JL, Gosselin P, Breville G, Brandle M, Henzen C, Leuppi JD, Kistler AD, Thurnheer R, Beuschlein F, Rudofsky G, Aeberli D, Villiger PM, Bohm S, Chifu I, Fassnacht M, Meyer G, Bojunga J, Cattaneo M, Sluka C, Schneider H, Rutishauser J; <<TOASST>> study group. Glucocorticoid withdrawal and glucocorticoid-induced adrenal insufficiency: Study protocol of the randomized controlled <<TOASST" (Taper Or Abrupt Steroid STop) multicenter trial. PLoS One. 2023 Apr 5;18(4):e0281585. doi: 10.1371/journal.pone.0281585. eCollection 2023.

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2017
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: May 5, 2017
• First Submitted That Met QC Criteria: May 11, 2017
• First Posted (Actual): May 15, 2017

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienediols; Prednisone
• Other Study ID Numbers: 2016-00487; ex14Rutishauser; 2024-517334-18-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No sharing planned

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No