Hypersensitivity Pneumonitis (HP) is an immune-mediated disease that manifests as interstitial lung disease after exposure to an inhaled antigen, often unidentified. HP can be classified as non-fibrotic or fibrotic HP. Fibrotic HP is associated with impaired quality of life (QoL) and reduced survival. The value and decline of forced vital capacity (FVC) are predictive factors of mortality in fibrotic HP. In most expert centres worldwide, corticosteroids are chosen as the first-line drug to treat fibrotic HP in clinical practice. However, this strategy has not been validated in a randomized controlled trial and it remains controversial, Moreover, corticosteroids are responsible for potentially serious adverse events. The hypothesis is that prednisolone, as a first-line treatment in fibrotic hypersensitivity pneumonitis (HP), slows down FVC decline compared to placebo. The main objective is to assess the efficacy of first-line treatment with prednisolone against placebo, on the 6-month change in FVC in percent of predicted value (% pred).The primary endpoint will be the absolute change in FVC (% pred) from baseline (inclusion visit,M0) to 6 months (M6) will be compared between the placebo arm and the prednisolone arm.
Hypersensitivity Pneumonitis (HP) is an immune-mediated disease that manifests as interstitial lung disease after exposure to an inhaled antigen, often unidentified. HP can be classified as non-fibrotic or fibrotic HP. Fibrotic HP is associated with impaired quality of life (QoL) and reduced survival. The value and decline of forced vital capacity (FVC) are predictive factors of mortality in fibrotic HP. In most expert centres worldwide, corticosteroids are chosen as the first-line drug to treat fibrotic HP in clinical practice. However, this strategy has not been validated in a randomized controlled trial and it remains controversial, Moreover, corticosteroids are responsible for potentially serious adverse events. The hypothesis is that prednisolone, as a first-line treatment in fibrotic hypersensitivity pneumonitis (HP), slows down FVC decline compared to placebo. The main objective is to assess the efficacy of first-line treatment with prednisolone against placebo, on the 6-month change in FVC in percent of predicted value (% pred).The primary endpoint will be the absolute change in FVC (% pred) from baseline (inclusion visit,M0) to 6 months (M6) will be compared between the placebo arm and the prednisolone arm. RUBY, is a national multicenter, randomized, double blind, placebo-controlled, superiority trial comparing the efficacy of prednisolone to placebo on the change in FVC (% pred) at 6 months. The investigators will randomly assign participants (1:1 ratio, stratification according to the identification of an inciting antigen) to receive oral prednisolone or placebo for a period of 6 months with a follow-up of 12 months. The primary endpoint will be assessed at Month 6. The investigators plan to include 120 participants.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
120
Active Comparator: prednisolone. Oral prednisolone will be administered and tapered over 6 months, according to the following schedule\*: 0.5 mg/kg/day (not exceeding 40mg/day) x 4 weeks, 0.25 mg/kg/day (not exceeding 20mg/day) x 4 weeks, 15 mg/day x 4 weeks, 10 mg/days x 4 weeks, 5 mg/day x 10 weeks
Dispersible placebo administered and tapered over 6 months according to the schedule detailed in the protocol
Absolute change in FVC (% pred)
Absolute change in FVC (% pred) from baseline (inclusion visit, M0) to 6 months (M6) will be compared between the placebo arm and the prednisolone arm.
Time frame: at month 6
Absolute change in FVC (% pred) according to the presence of a causal antigen at Month 6
Absolute change in FVC (% pred) from baseline (M0 or inclusion visit) to Month 6 according to the presence of a causal antigen.
Time frame: at Month 6
The change in FVC (% pred) at 12 months (M12)
Absolute and relative changes in FVC (% pred) between M0 and M12 will be compared between the placebo arm and the prednisolone arm.
Time frame: At month 12
The change in FVC (mL) at 12 months (M12)
Absolute and relative changes in FVC (mL) between M0 and M12 will be compared between the placebo arm and the prednisolone arm.
Time frame: At month 12
The changes in DLco (mmol/min/kPa) at Month 6
Time frame: At Month 6
The changes in DLco (% pred) at Month 6
Time frame: At Month 6
The changes in DLco (mmol/min/kPa) at Month 12
Time frame: At Month12
The changes in DLco (% pred) at Month 12
Time frame: At Month 12
The changes in distance walked during six-minute walt test 6MWT in meters (m) at Month 12
Changes in distance walked during 6MWT (m) from Month 0 to Month12 will be compared between the placebo arm and the prednisolone arm
Time frame: at Month12
The changes in distance walked during six-minute walt test 6MWT (% pred) at Month 12
Changes in distance walked during 6MWT (%pred) from Month 0 to Month12 will be compared between the placebo arm and the prednisolone arm
Time frame: At Month 12
The changes in distance walked during six-minute walt test 6MWT in meters (m) at Month 6
Changes in distance walked during 6MWT (m) from Month 0 to Month 6 will be compared between the placebo arm and the prednisolone arm
Time frame: At Month 6
The changes in distance walked during six-minute walt test 6MWT (%pred) at Month 6
Changes in distance walked during 6MWT (%pred) from Month 0 to Month 6 will be compared between the placebo arm and the prednisolone arm
Time frame: At Month 6
The change in health related QoL (the Saint Georges Hospital Respiratory Questionnaire (SGRQ) at Month 6
Changes in Respiratory QoL (the Saint Georges Hospital Respiratory Questionnaire (SGRQ)) from Month 0 to Month 6 will be compared between the placebo arm and the prednisolone arm
Time frame: At Month 6
The change in health related QoL (King's Brief ILD questionnaire) at Month 6
Changes in Respiratory QoL (King's Brief ILD questionnaire) from Month 0 to Month 6 will be compared between the placebo arm and the prednisolone arm
Time frame: At Month 6
The change in health related QoL (the Saint Georges Hospital Respiratory Questionnaire (SGRQ) at Month 12
Changes in Respiratory QoL (the Saint Georges Hospital Respiratory Questionnaire (SGRQ)) from Month 0 to Month 12 will be compared between the placebo arm and the prednisolone arm
Time frame: At Month 12
The change in health related QoL (King's Brief ILD questionnaire) at Month 12
Changes in Respiratory QoL (King's Brief ILD questionnaire) from Month 0 to Month 12 will be compared between the placebo arm and the prednisolone arm
Time frame: At Month 12
The proportion of patients who develop pulmonary progressive fibrosis (PPF) within 12 months
Time frame: Over 12 months
The proportion of subjects who experience acute exacerbation (AE) or require unplanned hospitalization within 12 months
Time frame: Over 12 months
Progression free survival (PFS) at 12 months
Time frame: At month 12
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