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High-Dose Intravenous Methylprednisolone for Hantavirus Cardiopulmonary Syndrome in Chile: A Double-Blind, Randomized Controlled Clinical Trial

2013; Oxford University Press; Volume: 57; Issue: 7 Linguagem: Inglês

10.1093/cid/cit394

1537-6591

Pablo Vial, Francisca Valdivieso, Marcela Ferrés, Raúl Riquelme, María Luisa Rioseco, Mario Calvo, Constanza Castillo, Ricardo Sobhie Diaz, Luis Scholz, Analía Cuiza, Edith Belmar, Carla Hernandez, Jessica Martínez, Sang-Joon Lee, Grégory Mertz, Juan Abarca, Vinko Tomicić, M. Eugenia Aracena, Ana Maria Rehbein, Soledad Velásquez, Victoria Lavin, Felipe Garrido, Pere Godoy, Constanza Martinez, Juan Carlos Chamorro, Jorge Contreras, Jury Hernandez, Marcelo Pino, Paola Villegas, Viviana Marcela Arias Zapata, Marisol León, Ivonne Vega, Irisol Otarola, Carlos Ortega, Elizabeth Daube, Doris Huecha, Alda Neira, I.Davila Ruiz, Margarita Nunez, Luz Monsalve, Henriette Chabouty, L. Zamorano Riquelme, Samia Palma, Raúl Bustos, R.Infante Miranda, Jovita Mardones, Nora Hernández, Yasna Betancur, L. Elso Sanhueza, Jaime Inostroza, S Donoso, Maritza Navarrete, Lily Acuña, Paulina Manriquez, Fabiola Castillo, Paola Unzueta, Teresa Aguilera, Carola Osorio, Veronica Yobanolo, J Mardones, Sandra Aranda, Soledad Carvajal, Moisés H. Sandoval, Soraya Daza, Felipe Vargas, Violeta Díaz, Mauricio Riquelme, Miriam Galián Muñoz, Andrea Carriel, Paola Lanino, Susana A. Hernandez, Patricia W. Schumacher, Lia Yañez, Claudia Marco, M Ehrenfeld, Iris Delgado, Susana P. Mejía, Cecilia Vial, Edward J. Bedrick,

Viral Infections and Outbreaks Research

Background. Andes virus (ANDV)–related hantavirus cardiopulmonary syndrome (HCPS) has a 35% case fatality rate in Chile and no specific treatment. In an immunomodulatory approach, we evaluated the efficacy of intravenous methylprednisolone for HCPS treatment, through a parallel-group, placebo-controlled clinical trial. Methods. Patients aged >2 years, with confirmed or suspected HCPS in cardiopulmonary stage, admitted to any of 13 study sites in Chile, were randomized by study center in blocks of 4 with a 1:1 allocation and assigned through sequentially numbered envelopes to receive placebo or methylprednisolone 16 mg/kg/day (≤1000 mg) for 3 days. All personnel remained blinded except the local pharmacist. Infection was confirmed by immunoglobulin M antibodies or ANDV RNA in blood. The composite primary endpoint was death, partial pressure of arterial oxygen/fraction of inspired oxygen ratio ≤55, cardiac index ≤2.2, or ventricular tachycardia or fibrillation within 28 days. Safety endpoints included the number of serious adverse events (SAEs) and quantification of viral RNA in blood. Analysis was by intention to treat. Results. Infection was confirmed in 60 of 66 (91%) enrollees. Fifteen of 30 placebo-treated patients and 11 of 30 methylprednisolone-treated patients progressed to the primary endpoint (P = .43). We observed no significant difference in mortality between treatment groups (P = .41). There was a trend toward more severe disease in placebo recipients at entry. More subjects in the placebo group experienced SAEs (P = .02). There were no SAEs clearly related to methylprednisolone administration, and methylprednisolone did not increase viral load. Conclusions. Although methylprednisolone appears to be safe, it did not provide significant clinical benefit to patients. Our results do not support the use of methylprednisolone for HCPS. Clinical Trials Registration. NCT00128180.