1. High-Dose Intravenous Methylprednisolone for Hantavirus Cardiopulmonary Syndrome in Chile: A Double-Blind, Randomized Controlled Clinical Trial
- Author
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Pablo A. Vial, Francisca Valdivieso, Marcela Ferres, Raul Riquelme, M. Luisa Rioseco, Mario Calvo, Constanza Castillo, Ricardo Díaz, Luis Scholz, Analia Cuiza, Edith Belmar, Carla Hernandez, Jessica Martinez, Sang-Joon Lee, Gregory J. Mertz, Juan Abarca, Vinko Tomicic, M. Eugenia Aracena, Ana Maria Rehbein, Soledad Velásquez, Victoria Lavin, Felipe Garrido, Paula Godoy, Constanza Martinez, Juan Carlos Chamorro, Jorge Contreras, Jury Hernandez, Marcelo Pino, Paola Villegas, Viviana Zapata, Marisol León, Ivonne Vega, Irisol Otarola, Carlos Ortega, Elizabeth Daube, Doris Huecha, Alda Neira, Ines Ruiz, M. Antonieta Nuñez, Luz Monsalve, Henriette Chabouty, Lorena Riquelme, Samia Palma, Raul Bustos, Ruben Miranda, Jovita Mardones, Nora Hernandez, Yasna Betancur, Ligia Sanhueza, Jaime Inostroza, Solange Donoso, Maritza Navarrete, Lily Acuña, Paulina Manriquez, Fabiola Castillo, Paola Unzueta, Teresa Aguilera, Carola Osorio, Veronica Yobanolo, Jorge Mardones, Sandra Aranda, Soledad Carvajal, Moisés Sandoval, Soraya Daza, Felipe Vargas, Violeta Diaz, Mauricio Riquelme, Miriam Muñoz, Andrea Carriel, Paola Lanino, Susana Hernandez, Patricia Schumacher, Lia Yañez, Claudia Marco, Mildred Ehrenfeld, Iris Delgado, Susana Rios, Cecilia Vial, and Edward Bedrick
- Subjects
Microbiology (medical) ,Adult ,Male ,medicine.medical_specialty ,Orthohantavirus ,Adolescent ,animal diseases ,viruses ,Anti-Inflammatory Agents ,Kaplan-Meier Estimate ,Hantavirus Pulmonary Syndrome ,Placebo ,Methylprednisolone ,Double-Blind Method ,Internal medicine ,Fraction of inspired oxygen ,medicine ,Clinical endpoint ,Humans ,Chile ,Articles and Commentaries ,Intention-to-treat analysis ,business.industry ,Surrogate endpoint ,virus diseases ,Middle Aged ,Surgery ,Clinical trial ,Infectious Diseases ,Treatment Outcome ,RNA, Viral ,Administration, Intravenous ,Female ,business ,Viral load ,medicine.drug - Abstract
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 benefi tt o patients. Our results do not support the use of methylprednisolone for HCPS. Clinical Trials Registration. NCT00128180.
- Published
- 2013