Clinical trial NCT03265405: Efficacy and Safety of Two Glucocorticoid Regimens in the Treatment of Sarcoidosis
Official title: Efficacy and Safety of Two Glucocorticoid Regimens in the Treatment of Sarcoidosis: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Sarcoidosis
Keywords: pulmonary sarcoidosis
corticosteroids
glucocorticoids
relapse
interstitial lung disease
diffuse parenchymal lung disease
immunosuppression
mediastinal lymphadenopathy
Lead sponsor: PGIMER
Sponsor class: UNKNOWN
First posted: 2017-08-29
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Relapse or treatment failure
timeFrame: 18 months
Secondary outcomes:
measure: Mean time to relapse/treatment failure
timeFrame: 18 months
measure: Response
timeFrame: 18 months
measure: Lung function early
timeFrame: 6 months
measure: Cumulative dose of prednisolone
timeFrame: 18 months
measure: Adverse effects
timeFrame: 18 months
measure: Change in the sarcoidosis-related quality-of-life assessed by the score on the Sarcoidosis Health Questionnaire at treatment completion
timeFrame: 6 months
measure: Change in the sarcoidosis-related quality-of-life assessed by the score on the Sarcoidosis Health Questionnaire at completion of follow-up
timeFrame: 18 months
measure: Change in fatigue severity assessed by the score on the Fatigue Assessment Scale at treatment completion
timeFrame: 6 months
measure: Change in fatigue severity assessed by the score on the Fatigue Assessment Scale at completion of follow-up
timeFrame: 18 months
measure: Lung function late
timeFrame: 18 months
Other outcomes:
Locations:
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical Education and Research
Study officials:
References: