RCT of Nintedanib in Fibrotic Sarcoidosis

Last updated: October 21, 2024
Sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh
Overall Status: Active - Recruiting

Phase

4

Condition

Sarcoidosis

Treatment

Nintedanib

Standard of care

Clinical Study ID

NCT06479603
INT/IEC/2023/SPL-1214
  • All Genders

Study Summary

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

Inclusion

Inclusion Criteria:

  • Age more than 18 years

  • Diagnosed with pulmonary sarcoidosis (clinico-radiologic presentation consistentwith pulmonary sarcoidosis (with or without extrapulmonary involvement) along withpresence of non-necrotising granulomatous inflammation in any of the involvedorgan/tissue and exclusion of a known cause for the granulomatous inflammation OR inthe absence of demonstration of granulomatous inflammation in tissues, a diagnosisof fibrotic pulmonary sarcoidosis on a multidisciplinary discussion (enrolment ofsubjects meeting the latter criteria will be capped at 20% of the planned samplesize)

  • Presence of signs of fibrosis on a computed tomography scan such as coarsereticulation, irregular lines, traction bronchiectasis, fibrotic masses, orhoneycombing involving ≥20% of the lung fields on visual examination

  • Having symptoms of breathlessness grade 1 or more on the modified Medical ResearchCouncil (mMRC) scale or persistent cough for more than 3 months

  • Forced vital capacity (FVC) <80% predicted value for the age and sex of thesubject using the reference equations for our subjects OR an exertional desaturationof 4% or more on a six-minute walk test (6MWT)

  • Receiving stable immunomodulatory treatment which includes standard of care drugssuch as glucocorticoids alone or in combination with methotrexate, azathioprine, ormycophenolate mofetil for more than 3 months in a stable dose

Exclusion

Exclusion Criteria:

  • Known cardiopulmonary or other comorbid illness that can explain the subject'sillness except group 3 pulmonary hypertension due to fibrotic pulmonary sarcoidosis

  • Hypersensitivity or contraindication to nintedanib (including high doseantiplatelets or anticoagulants, and bleeding diatheses)

  • Received an antifibrotic drug such as pirfenidone or nintedanib for ≥8 weeks in thepast one year

  • Baseline deranged liver function (alanine aminotransferase and aspartateaminotransferase or bilirubin more than 1·5 times the upper normal limit [except inthe case of Gilbert's syndrome])

  • Serum creatinine higher than 2.0 mg/dL

  • Uncontrolled congestive heart failure

  • Other serious concomitant medical illness (eg, cancer), chronic debilitating illness (other than chronic HP), or drug abuse

  • Pregnancy (documented by urine pregnancy test) or breastfeeding

  • Unwilling to participate in the study

Study Design

Total Participants: 120
Treatment Group(s): 2
Primary Treatment: Nintedanib
Phase: 4
Study Start date:
June 30, 2024
Estimated Completion Date:
January 31, 2026

Study Description

Setting: This prospective randomised controlled trial will be conducted in the Chest Clinic of the Department of Pulmonary Medicine, PGIMER, Chandigarh after approval from the ethics committee.

Study design: Open label parallel group randomized controlled trial Blinding: This will be an open label trial. Neither the subject nor the investigators will be blinded to the assigned group. The individual administering the Kings Sarcoid Questionnaire (KSQ) will be blinded to the group allocation.

Study participants: Diagnosed cases of pulmonary sarcoidosis of fibrotic phenotype who are on stable immunosuppressive therapy would be enrolled after screening for inclusion and exclusion criteria. Consecutive subjects with fibrotic sarcoidosis will be screened for this study. The subjects will undergo the following investigations: complete blood counts, liver and kidney function tests, and an electrocardiogram (ECG) in addition to a thin-section chest CT (if a recent scan within 6 months of screening is unavailable) or a positron emission tomography (PET) if indicated clinically, spirometry, and a six-minute walk test (6MWT). A venous blood sample (total of 10 mL) will be collected in plain and EDTA vials and stored for cytokine analysis and other testing.

Connect with a study center

  • Postgraduate Institute of Medical Education and Research

    Chandigarh,
    India

    Active - Recruiting

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