Journal Article

Glucocorticoid withdrawal and glucocorticoid-induced adrenal insufficiency: Study protocol of the randomized controlled «TOASST” (Taper Or Abrupt Steroid STop) multicenter trial

Gosselin, Pauline, Cattaneo, Marco, Schneider, Helga, Reny, Jean-Luc, Aeberli, Daniel, Blum, Claudine A., Henzen, Christoph, Mueller, Beat, Leuppi, Jörg D., Chifu, Irina, Komminoth, Mathis, Meyer, Gesine, Donath, Marc Y., Kistler, Andreas D., Rudofsky, Gottfried, Sluka, Constantin, Brändle, Michael, Schuetz, Philipp, Breville, Gautier, Fassnacht, Martin, Bojunga, Jörg, Beuschlein, Felix, Böhm, Stephan, Rutishauser, Jonas, Hepprich, Matthias, Villiger, Peter M., Thurnheer, Robert

2023

Overview

Despite the widespread use of glucocorticoids in inflammatory and autoimmune disorders, there is uncertainty about the safe cessation of long-term systemic treatment, as data from prospective trials are largely missing. Due to potential disease relapse or glucocorticoid-induced hypocortisolism, the drug is often tapered to sub-physiological doses rather than stopped when the underlying disease is clinically stable, increasing the cumulative drug exposure. Conversely, the duration of exposure to glucocorticoids should be minimized to lower the risk of side effects. We designed a multicenter, randomized, triple-blinded, placebo-controlled trial to test the clinical noninferiority of abrupt glucocorticoid stop compared to tapering after ≥28 treatment days with ≥420 mg cumulative and ≥7.5 mg mean daily prednisone-equivalent dose. 573 adult patients treated systemically for various disorders will be included after their underlying disease has been stabilized. Prednisone in tapering doses or matching placebo is administered over 4 weeks. A 250 mg ACTH-test, the result of which will be revealed a posteriori, is performed at study inclusion; all patients are instructed on glucocorticoid stress cover dosing. Follow-up is for 6 months. The composite primary outcome measure is time to hospitalization, death, initiation of unplanned systemic glucocorticoid therapy, or adrenal crisis. Secondary outcomes include the individual components of the primary outcome, cumulative glucocorticoid doses, signs and symptoms of hypocortisolism, and the performance of the ACTH test in predicting the clinical outcome. Cox proportional hazard, linear, and logistic regression models will be used for statistical analysis. This trial aims to demonstrate the clinical noninferiority and safety of abrupt treatment cessation after ≥28 days of systemic glucocorticoid therapy in patients with stabilized underlying disease. ClinicalTrials.gov Identifier: NCT03153527; EUDRA-CT: 2020-005601-48 https://clinicaltrials.gov/ct2/show/NCT03153527?term=NCT03153527&draw=2&rank=1.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: ACTH / Adrenal Insufficiency - chemically induced / Adrenocorticotropic Hormone / Adult / Autoimmune diseases / Birth control / Blood pressure / Care and treatment / Clinical trials / Corticosteroids / Diagnosis / Disease / Dosage / Dosage and administration / Drug dosages / Drug withdrawal / Drug withdrawal symptoms / Ethics / Glucocorticoids / Glucocorticoids - adverse effects / Glucocorticoids - therapeutic use / Health aspects / Health services / Humans / Hypothermia / Measurement / Medicine and Health Sciences / Methods / Multicenter Studies as Topic / Neoplasm Recurrence, Local - drug therapy / Patient education / Patients / People and Places / Placebos / Prednisone / Prednisone - adverse effects / Prednisone - therapeutic use / Prospective Studies / Randomized Controlled Trials as Topic / Regression analysis / Regression models / Risk factors / Side effects / Signs and symptoms / Statistical analysis / Steroids / Study Protocol / Tapering / Vital signs / Withholding Treatment