TOASST Study: Taper Or Abrupt Steroid STop?

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Kantonsspital Baden AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

6 Apr 2022 → ongoing

Decision date (initial)

2024-11-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-517334-18-00

EudraCT number

2020-005601-48

ClinicalTrials.gov

NCT03153527

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To perform the first adequately powered randomized, placebo controlled, multicenter noninferiority trial, comparing immediate termination of systemic glucocorticoid treatment with a tapering regime over four weeks. The hypothesis is tested that in patients treated with systemic glucocorticoids for various inflammatory disorders, rapid termination of treatment will not result in a worse clinical outcome than a tapering regime over four weeks.

Secondary objectives 2

1. To test whether the 250 mcg ACTH test predicts the need of unplanned glucocorticoid treatment during 6 months of follow-up.
2. To evaluate the correlation between clinical signs and symptoms of hypocortisolism and biochemical adrenocortical performance as assessed with the 250 mcg ACTH test.

Conditions and MedDRA coding

Inflammatory or autoimmune disorders

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Informed Consent as documented by signature
2. Age ≥ 18 years
3. Daily glucocorticoid dose ≥ 7.5 mg prednisone-equivalent at the time of inclusion
4. Therapy over ≥ 28 days,
5. ≥ 7.5 mg prednisone-equivalent average daily dose until time of inclusion,
6. cumulative glucocorticoid dose ≥ 420 mg prednisoneequivalent prior to inclusion
7. Tapering not or no longer mandatory to treat underlying disease

Exclusion criteria 13

1. Primary adrenal failure
2. Participation in another study with investigational drug within the 30 days preceding and during the present study,
3. Previous enrolment into the current study,
4. Enrolment of the investigator, his/her family members, employees and other dependent persons
5. Treatment with systemic depot glucocorticoids (e.g. intramuscular, epidural)
6. Incapability to administer glucocorticoid cover treatment in situations of stress
7. Inability or unwillingness to provide informed consent
8. Women who are pregnant or breast feeding,
9. Intention to become pregnant during the course of the study,
10. 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, as defined by the Clinical Trial Facilitation Group for the entire study duration, i.e. hormonal contraception with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion.
11. Known or suspected non-compliance
12. Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
13. Untreated hereditary galactose intolerance or lactase deficiency or glucose-galactose malabsorption.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 8

1. Time to first occurrence of individual components of the primary outcome
2. Cumulative overall systemic glucocorticoid dose
3. Cumulative systemic glucocorticoid dose administered to treat or prevent adrenal failure
4. Cumulative systemic glucocorticoid dose administered to treat relapse of disease, specified for each disease
5. 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: weakness, hypothermia, nausea, vomiting, abdominal pain, fatigue, dizziness, and blood pressure
7. Performance in 250 mcg ACTH (Synacthen®) test
8. In patients hospitalized at study entry: length of hospital stay

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Kantonsspital Baden AG

Sponsor organisation

Kantonsspital Baden AG

Address

Im Ergel 1

City

Baden

Postcode

5404

Country

Switzerland

Scientific contact point

Organisation

Kantonsspital Baden AG

Contact name

Prof. MD Jonas Rutishauser

Public contact point

Organisation

Kantonsspital Baden AG

Contact name

Prof. MD Jonas Rutishauser

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications