RCT of Nintedanib in Fibrotic Sarcoidosis
ConditionSarcoidosis, Pulmonary
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
AgeNot listed
SponsorPost Graduate Institute of Medical Education and Research, Chandigarh
About this trial
Sarcoidosis is generally managed with outdoor immune modulatory drugs, most commonly oral steroids and at times drugs like methotrexate or azathioprine as a steroid sparing agent.
Around 15-20% of sarcoidosis patient develop fibrosis of the lung parenchyma. The effect of antifibrotics in such patients needs more studies. Nintedanib has been used with good results in patients with fibrosing interstitial lung disease like IPF, SSC- ILD, and other progressive fibrosing ILD. By using nintedanib in fibrotic sarcoidosis it may be possible to limit the functional disability in these patients by slowing the rate of fibrosis and loss of lung function. The use of nintedanib if results in decrease in fibrosis and consequent decline in loss of lung function then it may be a safe and viable option for such patients.
The hypothesis of this study is that in patients with fibrotic sarcoidosis on standard of care anti-inflammatory therapy, nintedanib may help in reducing the rate of decline in lung function and progressive fibrosis. The aim is to evaluate the efficacy and safety of nintedanib in subjects with fibrotic sarcoidosis
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age more than 18 years
Diagnosed with pulmonary sarcoidosis (clinico-radiologic presentation consistent with pulmonary sarcoidosis (with or without extrapulmonary involvement) along with presence of non-necrotising granulomatous inflammation in any of the involved organ/tissue and exclusion of a known cause for the granulomatous inflammation OR in the absence of demonstration of granulomatous inflammation in tissues, a diagnosis of fibrotic pulmonary sarcoidosis on a multidisciplinary discussion (enrolment of subjects meeting the latter criteria will be capped at 20% of the planned sample size)
Presence of signs of fibrosis on a computed tomography scan such as coarse reticulation, irregular lines, traction bronchiectasis, fibrotic masses, or honeycombing involving ≥20% of the lung fields on visual examination
Having symptoms of breathlessness grade 1 or more on the modified Medical Research Council (mMRC) scale or persistent cough for more than 3 months
Disqualifiers
Known cardiopulmonary or other comorbid illness that can explain the subject's illness except group 3 pulmonary hypertension due to fibrotic pulmonary sarcoidosis
Hypersensitivity or contraindication to nintedanib (including high dose antiplatelets or anticoagulants, and bleeding diatheses)
Received an antifibrotic drug such as pirfenidone or nintedanib for ≥8 weeks in the past one year
Baseline deranged liver function (alanine aminotransferase and aspartate aminotransferase or bilirubin more than 1·5 times the upper normal limit [except in the case of Gilbert's syndrome])
Trial design
Design model
Parallel
Treatments tested in this trial
Nintedanib
DrugThe subjects will receive oral nintedanib. It will be prescribed to be taken after meals with 12 hrs gap between doses. The drug will be started at a dose of 100 mg twice daily. After 2 weeks, the dose will be titrated up to 150 mg twice daily, which will be continued till the end of 52 weeks. The standard-of-care immunosuppressive treatment will be continued along with the study drug (nintedanib). In case of intolerance to the 300 mg/day dose of nintedanib, the dose will be reduced to 100 mg twice daily. In case of severe adverse effects, the drug will be stopped and reintroduced after a period of up to 1-4 weeks. A dose of 100 mg twice daily will be started and continued. One attempt to titrate the dose up to 150 mg twice daily will be permitted.
Standard of care
DrugThe subjects will receive the standard-of-care immunosuppressive treatment alone that may include glucocorticoids and other steroid-sparing agents that the subject would already be receiving.
Treatment groups
120 Participants
are divided into 2 treatment groupsGroup A: NIntedanibActive comparator 1 intervention
Group B: Standard of careActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
The difference in the mean change in forced vital capacity (FVC) between the study groups
The FVC will be measured at baseline and 12 months using spirometry performed by an expert technician
Time frame
12 monthsSecondary outcomes
1
The difference in the mean change in forced expiratory volume in one sec (FEV1) between the study groups
The FEV1 will be measured at baseline and 12 months using spirometry performed by an expert technician
Time frame
12 months2
The difference in the mean change in the 6-minute walk distance (6MWD) between the study groups at the end of 12 months
The 6MWD will be measured at baseline and 12 months using a 6MWT performed by an expert technician
Time frame
12 months3
The difference in the mean change in the diffusing capacity of lung for carbon mono oxide (DLCO) between the study groups
The DLCO will be measured at baseline and 12 months and performed by an expert technician
Time frame
12 months4
Treatment-related adverse effects
Number of treatment-related adverse effects in each arm. The grading of adverse events according to the Common Terminology Criteria for Adverse Events version 5.0. These will include diarrhea, gastrointestinal disturbances, liver function test abnormalities, nausea, vomiting, and any other adverse effects reported by the study subject.
Time frame
12 monthsSponsors and contacts
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Source ClinicalTrials.gov