The prerequisite for participation in the study is a treatment duration of at least 4 weeks. If your treating physician wishes to discontinue prednisone therapy and you are still taking at least a daily dose of 7.5 mg (a corresponding dose of another preparation is also possible), you can be included. First, the body's own cortisol production is measured using the so-called "Synacthen test". The cortisol concentration in the blood is measured by taking a blood sample before and after administration of a stimulating hormone. The result remains under lock and key until the end of the study, even for the study physicians. They are then randomly assigned to one of two treatment groups: one group receives prednisone, which is continuously tapered off over 4 weeks, the other a placebo without active ingredient, which results in an abrupt discontinuation of the prednisone. Neither you nor the study doctor or another doctor knows which group you have been assigned to. After 1, 5, 12 and 26 weeks, you will be contacted by telephone and systematically asked about the course of your illness, your well-being and whether you need to take prednisone again. If you live near Basel, Lucerne or Aarau, we will also ask you to come to the hospital at these times for a physical examination and blood sample (including a "synacthen test"). Once the study is complete, we will analyze. whether the course of the disease and the need for unscheduled prednisone treatment differs between the two groups.
Aim of the study
No new drugs are being tested as part of the study. The study is intended to answer the question of whether, even after a longer period of treatment with a synthetic cortisol preparation (over at least 4 weeks with a total of at least 420 milligrams), the medication can be stopped without tapering off, without this resulting in an unfavorable course. This is the first study ever to directly compare immediate discontinuation with a tapering regimen. If the study hypothesis is confirmed, the unnecessary prolongation of prednisone treatments can be dispensed with in future, which would be desirable in view of the unfavorable side effect profile. If it turns out that stopping abruptly does have disadvantages compared to tapering, there would also be a scientifically sound basis for the latter procedure for the first time.
Who can take part?
Patients can take part in the study if they have been treated with a synthetic cortisol preparation (usually prednisone or prednisolone) for at least 4 weeks due to an inflammatory disease and if the treating physician wishes to discontinue this treatment. Examples of such diseases are: various forms of rheumatism (e.g. rheumatoid arthritis, giant cell arteritis, polymyalgia), inflammatory bowel diseases (e.g. Crohn's disease or ulcerative colitis), diseases of the haematopoietic system (e.g. autoimmune haemolytic anaemia), pneumonia (e.g. cryptogenic organizing pneumonia), or tumour diseases (e.g. lymphomas).
Procedure
Cortisol is an endogenous hormone produced in the adrenal glands that controls important metabolic functions and serves to maintain adequate blood pressure and blood sugar levels in stressful situations. Prednisone and other synthetically produced cortisol-like drugs are administered in tablet form or as injections to reduce inflammation in a variety of diseases. Examples are rheumatic diseases, inflammatory bowel diseases, certain diseases of the hematopoietic system, diseases of the nervous system, or tumor diseases. Prednisone has many adverse drug effects, such as weight gain, weakening of bone and connective tissue, increased blood pressure, or increased blood sugar levels and even diabetes. A frequently observed side effect of prednisone is the suppression of the body's own production of cortisol. This effect lasts beyond the end of prednisone therapy. However, it is impossible to predict in individual cases whether such suppression of adrenal function will occur or not and how long it will last. For this reason, a laboratory test is often carried out in clinical medicine before the planned termination of prednisone therapy, which answers the question. In this so-called Synacthen test, a second hormone, Synacthen, is injected, which stimulates the adrenal glands to produce and release cortisol into the bloodstream, and the cortisol level in the blood is measured 30 and 60 minutes after the injection. If the measured cortisol levels are low, prednisone is not discontinued abruptly, but the dose is reduced in small steps before it is finally stopped completely after a few weeks. Although this procedure is medically plausible, it has not yet been scientifically proven. It has not been investigated at what dose, in what steps and over what duration prednisone medication should be discontinued. It is not even clear whether it is even necessary to balance them out, even if low cortisol levels are measured in the Synacthen test. In our own study of over 200 patients who were treated with prednisone, we did not observe any unfavorable consequences even if the result of the Synacthen test was inadequate and despite abrupt discontinuation of therapy, and specific questioning about symptoms of cortisol deficiency showed no difference to people with a normal test result. It can therefore be assumed that in many cases where prednisone is discontinued, treatment is unnecessarily prolonged for weeks, which is known to increase the risk of side effects. The present study is therefore intended to test the hypothesis that even after a longer treatment period with prednisone (at least 4 weeks with a total of at least 420 milligrams), the drug can be stopped abruptly without resulting in a worse outcome. The observation period is 6 months after study inclusion. In order to obtain sufficient information, 573 patients are required for the study, half of whom will have their prednisone treatment tapered off over four weeks and half of whom will have it stopped abruptly. Participants in the latter group received sham preparations with the same appearance (placebo) instead of prednisone. Group allocation is decided by chance, and neither the participants nor the investigator know which group they belong to (double-blind principle). To assess progression, the time elapsed until the first occurrence of one or more of the following events will be compared in both groups: Hospitalization, signs of cortisol deficiency, death, or unplanned re-treatment with prednisone or another cortisol-like drug (for example, due to a relapse of the disease originally treated with prednisone). It will also be investigated whether the synacthen test is suitable for predicting the occurrence of these events. As a precaution, prednisone tablets are given to all participants; these are to be taken in situations with an increased need for cortisol, for example in the case of feverish illnesses (so-called stress prophylaxis).
This is the first study ever to directly compare the discontinuation of prednisone with a tapering regimen. If the study hypothesis is confirmed, the unnecessary prolongation of prednisone treatments can be dispensed with in future, which would be desirable in view of the unfavorable side effect profile. If it turns out that stopping abruptly does have disadvantages compared to tapering, there would also be a scientifically sound basis for the latter procedure for the first time.
Compensation
If you take part in this study, it is free of charge for you. We will reimburse you for expenses such as travel expenses that are only due to your participation in the study.
Original study name
Glucocorticoid withdrawal and glucocorticoid-induced adrenal insufficiency: a randomized controlled multicenter trial ("Taper Or Abrupt Steroid STop")
BASEC number
2016-00487
Sponsors
Swiss National Science Foundation