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Taper Or Abrupt Steroid Stop: TOASSTtrial (TOASST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03153527
Recruitment Status : Recruiting
First Posted : May 15, 2017
Last Update Posted : May 4, 2021
Sponsor:
Collaborators:
Kantonsspital Baselland Bruderholz
Swiss National Science Foundation
HEMMI Stiftung Switzerland
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

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.

Condition or disease Intervention/treatment Phase
Inflammatory Disorder Autoimmune Drug: Prednisone Other: Placebo Arm Phase 4

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 573 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Blinding of trial participants, treating physicians, study doctors, study nurses, outcome assessors and data analysts will be ensured by using identical-looking placebo, packaged in identical vials as the prednisone verum. Vials will be labeled with "Prednisone or Placebo" in an identical fashion.
Primary Purpose: Treatment
Official Title: Glucocorticoid Withdrawal and Glucocorticoid-induced Adrenal Insufficiency: a Randomized Controlled Multicenter Trial
Actual Study Start Date : May 31, 2017
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Steroids
Drug Information available for: Prednisone

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.




Primary Outcome Measures :
  1. Time to any incidence [ Time Frame: up to 6 months ]
    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.


Secondary Outcome Measures :
  1. Time to specific incidence [ Time Frame: up to 6 months ]
    Time to first occurrence of individual components of the primary outcome;

  2. Cumulative overall systemic glucocorticoid dose [ Time Frame: up to 6 months ]
    Cumulative overall systemic glucocorticoid dose

  3. Cumulative systemic glucocorticoid dose administered to treat or prevent adrenal failure [ Time Frame: up to 6 months ]
    Cumulative systemic glucocorticoid dose administered to treat or prevent adrenal failure

  4. Cumulative systemic glucocorticoid dose administered to treat relapse [ Time Frame: up to 6 months ]
    Cumulative systemic glucocorticoid dose administered to treat relapse of disease, specified for each disease

  5. General health status [ Time Frame: assessed at days 1, 7, 28, 35, 90,180 ]
    General health status as self-assessed by the participant on a visual analog scale (VAS) from 0 to 100

  6. Score of symptoms and signs of hypocortisolism [ Time Frame: up to 6 months ]
    Score of symptoms and signs of hypocortisolism: weakness, hypothermia, nausea, vomiting, abdominal pain, fatigue, dizziness, Blood pressure, serum Na and serum glucose concentrations.

  7. Performance in 250 mcg Synacthen® test [ Time Frame: up to 6 months ]
    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

  8. In patients hospitalized at study entry: length of hospital stay [ Time Frame: up to 6 months ]
    In patients hospitalized at study entry: length of hospital stay



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03153527


Contacts
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Contact: Jonas Rutishauser, Prof MD +41-56-486 25 16 j.rutishauser@unibas.ch

Locations
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Germany
University Hospital Würzburg Recruiting
Würzburg, Germany, 97080
Contact: Martin Fassnacht, Prof Dr. med.    +49-931-201-39201    Fassnacht_M@ukw.de   
Principal Investigator: Martin Fassnacht, Prof Dr. med.         
Switzerland
Departement of Internal Medicine, Kantonsspital Aarau Recruiting
Aarau, Switzerland, 5001
Contact: Philip Schuetz, Prof Dr med    +41 62 838 95 24    schuetzph@gmail.com   
Kantonsspital Baden Recruiting
Baden, Switzerland, 5404
Contact: Jonas Rutishauser, Prof. Dr. MD    +41-56-486 25 16    j.rutishauser@unibas.ch   
Endocrinology/Diabetology/Metabolism; University Hospital Basel Recruiting
Basel, Switzerland, 4031
Contact: Marc Donath, Prof Dr Med    +41 61 265 50 78    marc.donath@usb.ch   
Department of Rheumatology, Immunology, and Allergology, Inselspital Recruiting
Bern, Switzerland, 3010
Contact: Daniel Aeberli, Prof Dr med    +41-31- 632 07 32    daniel.aeberli@insel.ch   
Division of Gastroenterology, Spital Bülach AG Recruiting
Bülach, Switzerland, 8180
Contact: Stephan Böhm, PD Dr. med.    +41 44 863 2966    stephan.boehm@spitalbuelach.ch   
Principal Investigator: Stephan Böhm, PD Dr. med.         
Kantonsspital Frauenfeld Recruiting
Frauenfeld, Switzerland, 8501
Contact: Andreas Kistler, PD Dr. med.    +41 52 723 76 43    andreas.kistler@stgag.ch   
Principal Investigator: Andreas Kistler, PD Dr. med.         
Geneva University Hospitals Recruiting
Geneva, Switzerland, 1205
Contact: Jean-Luc Reny, Prof. Dr. med.    +41 22 372 90 52      
Principal Investigator: Jean-Luc Reny, Prof. Dr. med.         
Center for Primary Health Care,University of Basel, Kantonsspital Baselland Recruiting
Liestal, Switzerland, 4410
Contact: Andreas Zeller, Prof Dr med         
Contact    +41-61-925 20 75    andreas.zeller@unibas.ch   
Internal Medicine, Kantonsspital Baselland/Liestal Recruiting
Liestal, Switzerland, 4410
Contact: Jörg Leuppi, Prof Dr med    +41-61-925 21 80    joerg.leuppi@ksbl.ch   
Department of Internal Medicine, Kantonsspital Münsterlingen Recruiting
Münsterlingen, Switzerland, 8596
Contact: Robert Thurnheer    +41 71 686 21 75    robert.thurnheer@stgag.ch   
Principal Investigator: Robert Thurnheer, Prof. Dr. med         
Stoffwechselzentrum, Kantonsspital Olten Recruiting
Olten, Switzerland, 4600
Contact: Gottfried Rudofsky, Prof. Dr. med    +41-62-311 44 94    gottfried.rudofsky@spital.so.ch   
Department of Internal Medicine, Kantonsspital St. Gallen Recruiting
St. Gallen, Switzerland, 9007
Contact: Michael Brändle, Prof Dr med    +41-71-494 61 21    michael.braendle@kssg.ch   
Dept. of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Recruiting
Zürich, Switzerland, 8091
Contact: Felix Beuschlein, Prof Dr med    : +41-44-255 36 25    felix.beuschlein@usz.ch   
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Kantonsspital Baselland Bruderholz
Swiss National Science Foundation
HEMMI Stiftung Switzerland
Investigators
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Principal Investigator: Jonas Rutishauser, Prof MD Departement Medizin, Kantonsspital Baden
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Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT03153527    
Other Study ID Numbers: 2016-00487; ex14Rutishauser
First Posted: May 15, 2017    Key Record Dates
Last Update Posted: May 4, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No sharing planned

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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
Additional relevant MeSH terms:
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Prednisone
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents