Pirfenidone in post-COVID-19 pulmonary fibrosis (FIBRO-COVID): a phase 2 randomised clinical trial

被引:1
作者
Bermudo-Peloche, Guadalupe [1 ,2 ,3 ]
Del Rio, Belen [4 ]
Vicens-Zygmunt, Vanesa [1 ,2 ,3 ]
Bordas-Martinez, Jaume [1 ,2 ]
Hernandez, Marta [1 ,3 ]
Valenzuela, Claudia [2 ,5 ]
Laporta, Rosalia [2 ,6 ]
Bobillo, Juan Rigual [7 ]
Portillo, Karina [2 ,8 ]
Millan-Billi, Paloma [8 ]
Balcells, Eva [2 ,9 ]
Badenes-Bonet, Diana [9 ]
Bolivar, Santi [4 ]
Rodriguez-Portal, Jose-Antonio [2 ,10 ]
Ramirez, Cecilia Lopez [10 ]
Tomas, Laura [11 ]
Roitegi, Koral Fernandez de [11 ]
Sellares, Jacobo [2 ,12 ]
Castillo, Diego [2 ,13 ]
Gonzalez, Jessica [2 ,14 ]
Barril, Silvia [14 ]
Gutierrez-Rodriguez, Yasmina [1 ,3 ]
Caballero, Paloma [15 ]
Alarcon, Javier [16 ]
Penafiel, Judith [17 ]
Sanz-Santos, Jose [18 ]
Blavia, Rosana [19 ]
Caupena, Cristina [20 ]
Segovia, Pilar [21 ]
Santos-Perez, Salud [1 ,2 ,3 ]
Ferrer-Artola, Anna [3 ,22 ]
Badia, Maria B. [3 ,22 ]
Hereu, Pilar [3 ,23 ]
Fuentes, Mireya [1 ,2 ,3 ]
Montes-Worboys, Ana [1 ,2 ,3 ]
Franquet, Tomas [24 ]
Luburich, Patricio [2 ,3 ,4 ]
Molina-Molina, Maria [1 ,2 ,3 ]
机构
[1] Bellvitge Univ Hosp, Resp Dept, Interstitial Lung Dis Unit, Lhospitalet De Llobregat, Barcelona, Spain
[2] Natl Network Res Resp Dis CIBERES, Barcelona, Spain
[3] Bellvitge Biomed Res Inst IDIBELL, Barcelona, Spain
[4] Univ Barcelona, Bellvitge Univ Hosp, Radiol Dept, Interstitial Lung Dis Unit, Lhospitalet De Llobregat, Barcelona, Spain
[5] Hosp La Princesa, Resp Dept, Interstitial Lung Dis Unit, Madrid, Spain
[6] Hosp Puerta Hierro, Resp Dept, Majadahonda, Spain
[7] Univ Alcala IRYCIS, Hosp Ramon Y Cajal, Resp Dept, Madrid, Spain
[8] Hosp Germans Trias i Pujol, Resp Dept, Badalona, Spain
[9] Univ Pompeu Fabra UPF, Hosp del Mar, Resp Dept, Dept Med & Life Sci, Barcelona, Spain
[10] Hosp Virgen del Rocio, Resp Dept, Interstitial Lung Dis Unit, Seville, Spain
[11] Hosp Txagorritxu, Resp Dept, Vitoria, Spain
[12] Hosp Clin Barcelona, Resp Dept, Interstitial Lung Dis Unit, Barcelona, Spain
[13] Hosp St Pau i Santa Creu, Resp Dept, Barcelona, Spain
[14] Univ Hosp Arnau de Vilanova & Santa Maria, Translat Res Resp Med, IRBLleida, Lleida, Spain
[15] Hosp La Princesa, Radiol Dept, Interstitial Lung Dis Unit, Madrid, Spain
[16] Hosp Ramon & Cajal, Dept Radiol, Interstitial Lung Dis Unit, Madrid, Spain
[17] IDIBELL, Dept Biostat, Lhospitalet De Llobregat, Barcelona, Spain
[18] Hosp Mutua Terrassa, Resp Dept, Terrassa, Spain
[19] Hosp Moises Broggi, Resp Dept, St Joan Despi, Spain
[20] Hosp Gen Parc Sanit St Joan de Deu, Resp Dept, St Boi De Llobregat, Spain
[21] Hosp Figueres, Resp Dept, Figueres, Spain
[22] Univ Hosp Bellvitge, Dept Pharm, Grp Invest Farmacoterapia Farmacogenet & Tecnol Fa, IDIBELL,Programa Sistema Digest Diagnost Farmacoge, Barcelona, Spain
[23] Univ Barcelona, Bellvitge Univ Hosp, Clin Pharmacol Dept, Clin Res & Clin Trial Unit,IDIBELL, Barcelona, Spain
[24] Hosp St Pau & Santa Creu, Dept Radiol, Barcelona, Spain
关键词
D O I
10.1183/13993003.02249-2024
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Background Patients with severe COVID-19 may develop lung fibrosis. Pirfenidone is an anti-fibrotic drug approved for idiopathic pulmonary fibrosis. The efficacy and safety of pirfenidone in patients with fibrotic interstitial lung changes after recovery from severe COVID-19 pneumonia were evaluated. Methods This was a phase 2, double-blind, placebo-controlled, Spanish multicentre clinical trial. Patients were randomised to receive pirfenidone or placebo (2:1) for 24 weeks. The primary end-point was the proportion of patients that improved, considered when percentage change in forced vital capacity (FVC) was >= 10% and/or any reduction in the fibrotic score on chest high-resolution computed tomography (HRCT). Secondary end-points included health-related quality of life (HRQoL), exercise capacity and drug safety profile. Results From 119 eligible patients, 113 were randomised and 103 were analysed ( pirfenidone n=69 and placebo n=34). Most patients were male (73.5%) and were receiving low-dose prednisone; mean age was 63.7 years and mean body mass index was 29 kg<middle dot>m-2. The percentage of patients that improved was similar in the pirfenidone and placebo groups (79.7% versus 82.3%, respectively). The mean predicted FVC increased by 12.74 +/- 20.6% with pirfenidone and 4.35 +/- 22.3% with placebo (p=0.071), and the HRCT (%) fibrotic score decreased by 5.44 +/- 3.69% with pirfenidone and 2.57 +/- 2.59% with placebo (p=0.52). Clinically meaningful improvement in HRQoL was not statistically different (55.2% in the pirfenidone group and 39.4% in the placebo group). Exercise capacity, adverse events and hospitalisations were similar between groups. No deaths were reported. Conclusions The overall improvements in lung function and HRCT fibrotic score after 6 months with pirfenidone were not significantly different than with placebo.
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