Clinical trial NCT05626387: An RCT of Mycophenolate Mofetil (MMF) in Fibrotic Hypersensitivity Pneumonitis
Official title: Mycophenolate Mofetil and Prednisolone Versus Prednisolone Alone in Fibrotic Hypersensitivity Pneumonitis: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Hypersensitivity Pneumonitis
Keywords: HP
interstitial lung disease
ILD
diffuse parenchymal lung disease
Lead sponsor: PGIMER
Sponsor class: UNKNOWN
First posted: 2022-11-23
Enrollment: 144
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: To our knowledge, there is no randomized controlled trial assessing the efficacy of mycophenolate mofetil (MMF) in the treatment of HP. We aim to perform a randomized study to assess the efficacy and safety of a regimen consisting of MMF and prednisolone against a regimen consisting of prednisolone alone for treating fibrotic HP. We hypothesize that the treatment of patients with fibrotic HP with MMF and prednisolone will be more effective and safer than treatment with prednisolone alone.

Detailed description: Hypersensitivity pneumonitis (HP) is a complex immunologically-mediated interstitial lung disease (ILD) resulting from sensitization to an inhaled antigen. It may be categorized into acute (acute/subacute) or chronic forms based on the duration of disease or evidence of chronicity on radiological or pathological findings. Lately, the American Thoracic Society (ATS) Guidelines 2020 has endorsed a new classification of HP into non-fibrotic and fibrotic types based on the absence or presence of signs of fibrosis on chest computed tomography (CT) or histology. According to a survey study, about three-fourths of respiratory physicians believe that fibrotic HP should be treated with glucocorticoids as the treatment of first choice, which also reflects the practice in most centers worldwide. However, there is some evidence that glucocorticoids may not be effective in the long-term treatment of fibrotic HP. Also, glucocorticoids are associated with several adverse effects especially when used over a long duration. Therefore, most experts recommend that glucocorticoids should be tapered to the lowest possible dose after a trial of about three months in chronic/fibrotic HP.

Hypersensitivity pneumonitis is characterized by an exaggerated T cell-mediated immune inflammatory response (T-lymphocytic alveolitis) due to increased migration, local proliferation, and decreased programmed cell death of lymphocytes. Mycophenolate mofetil (MMF) is an immunosuppressive drug that acts by inhibiting the proliferation of T-lymphocytes and suppressing the recruitment of lymphocytes and monocytes into the sites of inflammation. Therefore, MMF is likely to be effective in the treatment of HP. There are only a few retrospective studies on the efficacy of MMF in the treatment of HP. To our knowledge, there is no randomized controlled trial assessing the efficacy of MMF in the treatment of HP.

We aim to perform a randomized study to assess the efficacy and safety of a regimen consisting of MMF and prednisolone against a regimen consisting of prednisolone alone for treating fibrotic HP. We hypothesize that the treatment of patients with fibrotic HP with MMF and prednisolone will be more effective and safer than treatment with prednisolone alone.

Eligibility criteria: Inclusion Criteria:

i. A diagnosis of fibrotic hypersensitivity pneumonitis according to the criteria proposed in the American Thoracic Society Guideline 2020 ii. Screening FVC at least 40% of the predicted value iii. Able to provide a written, informed consent for participation in the trial

Exclusion Criteria:

i. Baseline FVC \<40% predicted ii. Leucopenia (white blood cell count \<4·0 × 10\^9 per L), significant thrombocytopenia (platelet count \<100 × 10\^9 per L), or clinically significant anemia (hemoglobin \<10 g/dL) iii. Baseline liver transaminases (alanine aminotransferase and aspartate aminotransferase) or bilirubin more than 1·5 times the upper normal limit (except in the case of Gilbert's syndrome) iv. Serum creatinine higher than 2.0 mg/dL v. Uncontrolled congestive heart failure vi. Receipt of prednisolone (more than or equal to 10 mg/day, or equivalent), in the 4 weeks before randomization vii. Prior use of prednisolone (more than or equal to 10 mg/day, or equivalent), MMF, azathioprine, cyclophosphamide, cyclosporine or any other non-glucocorticoid immunosuppressant drug, or antifibrotic agents for more than 12 weeks in the previous year viii. Active infection (lung or elsewhere) whose management would be compromised by MMF or prednisolone ix. Other serious concomitant medical illness (eg, cancer), chronic debilitating illness (other than chronic HP), or drug abuse x. Pregnancy (documented by urine pregnancy test) or breastfeeding xi. Unwilling to participate in the study

Primary outcomes:
measure: Lung function (FVC) decline
timeFrame: 52 weeks
Secondary outcomes:
measure: FEV1 decline
timeFrame: 52 weeks
measure: Severity of breathlessness
timeFrame: 52 weeks
measure: Six-minute walk distance
timeFrame: 52 weeks
measure: Disease specific health status
timeFrame: 52 weeks
measure: Diffusion capacity
timeFrame: 52 weeks
measure: Proportion of subjects who develop progressive pulmonary fibrosis (PPF)
timeFrame: 52 weeks
measure: Proportion of subjects who develop acute exacerbation(s)
timeFrame: 52 weeks
measure: Treatment-emergent adverse effects
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical Education and Research
Study officials:
affiliation: Postgraduate Institute of Medical Education and Research, Chandigarh, India
name: Sahajal Dhooria, MD, DM
role: PRINCIPAL_INVESTIGATOR
References: