Efficacy and Safety of Two Glucocorticoid Regimens in the Treatment of Sarcoidosis

Sarcoidosis Clinical Trial

— SARCORT  

Official title:

Efficacy and Safety of Two Glucocorticoid Regimens in the Treatment of Sarcoidosis: a Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03265405
• Other study ID #: INT/IEC/2017/299
• Status: Completed
• Phase: Phase 4
• Start date: April 1, 2017
• Est. completion date: October 31, 2022

Study information

• Verified date: January 2023
• Source: Postgraduate Institute of Medical Education and Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

For pulmonary sarcoidosis, the initial dose recommended by the joint statement of the American Thoracic Society (ATS), European Respiratory Society (ERS), and The World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) is 20-40 mg per day.5 The exact dose and duration of treatment for sarcoidosis are unknown.4 We hypothesize that a higher dose of 40 mg per day as compared to a 20 mg/day dose of prednisone will be more effective in preventing post-treatment relapse by effective initial suppression of the granulomatous inflammation and reduction of the disease load. In this study, we compare the efficacy and safety of medium dose (40 mg/day prednisone) and low dose (20 mg/day prednisone) glucocorticoids in the treatment of acute sarcoidosis.

Description:

Glucocorticoids are the cornerstone of treatment of sarcoidosis and are used as the first-line agents in patients requiring immunosuppressive therapy.4 The optimal dose and duration of glucocorticoids is an unresolved issue. For pulmonary sarcoidosis, the initial dose recommended by the joint statement of the ATS/ERS/WASOG is 20-40 mg per day.5 The duration of treatment recommended is at least one year. However, mild disease of recent onset may respond to a shorter duration of treatment. Further, as most of the toxic effects of glucocorticoids are cumulative, the dose and duration of steroids need to be kept to a minimum to balance the benefit and risks of treatment. Two large studies performed about two decades ago used an initial dose of 30 mg and 20 mg respectively for treating acute sarcoidosis. While the British Thoracic Society employed steroid treatment (initial dose 30 mg/day) for one year, in the Finnish study, oral glucocorticoids (initial dose 20 mg/day) were administered for three months and were followed by inhaled budesonide.3,6 In a recent Delphi study of experts, 37% and 20% of the experts used an initial prednisone equivalent dose of 40 mg per day and 20 mg per day regardless of weight, respectively.7 About 23% used doses of 20 mg, 30 mg, or 40 mg per day depending on weight. However, consensus was reached that a dose higher than 40 mg per day is not required. Apart from the initial response to glucocorticoids in symptoms and lung function, the rate of relapse after cessation of treatment is an important outcome in the management of sarcoidosis. The exact dose and duration of treatment for sarcoidosis are unknown.4 We hypothesize that a higher dose of 40 mg per day as compared to a 20 mg/day dose of prednisone will be more effective in preventing post-treatment relapse by effective initial suppression of the granulomatous inflammation and reduction of the disease load. In this study, we compare the efficacy and safety of medium dose (40 mg/day prednisone) and low dose (20 mg/day prednisone) glucocorticoids in the treatment of acute sarcoidosis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: October 31, 2022
• Est. primary completion date: October 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Computed tomography of the chest consistent with a diagnosis of sarcoidosis of the lung/mediastinal lymph nodes

2. Diagnosis of sarcoidosis made on cytological or histological samples

3. Having significant symptoms requiring immunosuppressive treatment and/or having reduced lung function (defined as forced vital capacity or forced expiratory volume in one second (FEV1) less than 80% predicted) or an extrathoracic manifestation of the disease requiring treatment with low-medium dose glucocorticoids

4. Onset of symptoms within two years of study entry

Exclusion Criteria:

1. Pregnant or lactating women

2. Subjects having any manifestation requiring high dose steroid treatment (this includes symptomatic neurosarcoidosis, life threatening cardiac sarcoidosis, vision threatening posterior uveitis or other forms of vision threatening ocular sarcoidosis)

3. Having absolute contraindication for prednisone in a dose of 40 mg/day (this includes untreated glaucoma, uncontrolled diabetes mellitus, untreated infections, untreated severe psychiatric disorders)

4. Unwilling to participate in the study

5. Having received glucocorticoids (prednisolone equivalent >15 mg/day) for more than three weeks in the preceding two years

Related Conditions & MeSH terms

• Sarcoidosis

Intervention

Drug:
• Low dose prednisolone
An initial dose of 20 mg/day will be administered for 8 weeks, followed by 15 mg/day for 8 weeks, 10 mg/day for 4 weeks, and 5 mg/day for 4 weeks, after which the drug will be tapered over 2 weeks and discontinued.
• Medium dose prednisolone
An initial dose of 40 mg/day will be administered for 4 weeks, followed by 30 mg/day for 4 weeks, 20 mg/day for 4 weeks, 15 mg/day for 4 weeks, 10 mg/day for 4 weeks, and 5 mg/day for 4 weeks, after which the drug will be tapered over 2 weeks and discontinued.

Locations

Country	Name	City	State
India	Postgraduate Institute of Medical Education and Research	Chandigarh

Sponsors (1)

Lead Sponsor	Collaborator
Postgraduate Institute of Medical Education and Research

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relapse or treatment failure	The proportion of subjects with a relapse or treatment failure in the two study groups (initial dose 40 mg/day versus 20 mg/day of prednisone) at the end of 18 months	18 months
Secondary	Mean time to relapse/treatment failure	The difference between the mean time to relapse/treatment failure in the study groups	18 months
Secondary	Response	The proportion of subjects with worsening, stabilization, improvement or resolution of the disease in the study groups at the end of 18 months	18 months
Secondary	Lung function early	The difference in the mean change in forced vital capacity between the study groups at the end of 6 months	6 months
Secondary	Cumulative dose of prednisolone	The difference in the mean cumulative dose of prednisolone between the study groups at the end of 18 months	18 months
Secondary	Adverse effects	The adverse effects of treatment (acne, weight gain, hyperglycemia, hypertension, adrenal insufficiency, osteoporosis and any other adverse effects related to prednisolone) between the study groups at the end of 18 months	18 months
Secondary	Change in the sarcoidosis-related quality-of-life assessed by the score on the Sarcoidosis Health Questionnaire at treatment completion	The Sarcoidosis Health Questionnaire is a health-related quality-of-life questionnaire for patients with sarcoidosis. Higher scores reflect better quality-of-life	6 months
Secondary	Change in the sarcoidosis-related quality-of-life assessed by the score on the Sarcoidosis Health Questionnaire at completion of follow-up	The Sarcoidosis Health Questionnaire is a health-related quality-of-life questionnaire for patients with sarcoidosis. Higher scores reflect better quality-of-life	18 months
Secondary	Change in fatigue severity assessed by the score on the Fatigue Assessment Scale at treatment completion	The Fatigue Assessment Scale is a validated instrument for assessing sarcoidosis-related fatigue. Higher scores reflect more severe fatigue	6 months
Secondary	Change in fatigue severity assessed by the score on the Fatigue Assessment Scale at completion of follow-up	The Fatigue Assessment Scale is a validated instrument for assessing sarcoidosis-related fatigue. Higher scores reflect more severe fatigue	18 months
Secondary	Lung function late	The difference in the mean change in forced vital capacity between the study groups at the end of18 months	18 months