1188. Controlled Trial of High-Dose Intravenous  Methylprednisolone for Hantavirus Cardiopulmonary Syndrome (HCPS) in Chile
Session: Poster Abstract Session: New Approaches to Anti-Viral Therapy
Saturday, October 22, 2011
Room: Poster Hall B1
Handouts
  • MP treatment IDSA 6_10_11.pdf (487.4 kB)
  • Background: 

    Andes virus (ANDV) is the etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in Chile, where there have been 680 cases and 238 deaths (35%) through 2010.  Competing hypotheses for the pathogenesis of respiratory failure and shock have led to evaluation of antiviral and immunomodulatory therapy.  Here we report a placebo-controlled trial of intravenous methylprednisolone (MP) for patients with suspected HCPS in the cardiopulmonary stage.    

    Methods: 

    Patients were randomized to receive placebo or MP 8 mg/kg (<500 mg) over 1 hour, the same dose over 23 hours, and 16 mg/kg (< 1000 mg) over 24 hours on days 2 and 3.  Infection was confirmed by serum IgM assay or detection of ANDV RNA in blood. The primary endpoint was progression to death, PaO2/FiO2 ratio <55, cardiac index <2.2, or ventricular tachycardia or fibrillation within 28 days of entry. Safety endpoints included the number of serious adverse events possibly related to treatment and serial quantification of cell-associated viral RNA.

    Results: 

    66 subjects were enrolled at 8 study centers between 2003-10, and acute ANDV infection was confirmed in 60 (91%).  Mortality was 33.3% (20/60) in those with HCPS, including 12/30 placebo- and 8/30 MP-treated patients (p=0.412); 14 (46.7%) of 30 placebo recipients progressed to the primary endpoint versus 8 (26.7%) of 30 MP recipients (p=0.180).  SOFA scores were higher in placebo recipients at entry.  After adjustment for differences at entry, SOFA scores were similar on days 1 and 2, lower in the MP group on days 3 and 4 and similar on days 5-7. Serious adverse events, primarily thrombocytopenia and shock, were more common in placebo- (47%) than in MP-treated patients (22%, p=0.003).  One placebo-treated patient died from a ventilator-associated pneumonia. MP treatment did not increase viral load.

    Conclusion: 

    Treatment of HCPS with high-dose MP appears safe. However, treatment did not provide significant clinical benefit to patients, and our results do not support the use of  methylprednisolone for HCPS.  While we reached our target enrollment, the study was not powered to detect a difference in mortality or secondary endpoints. Higher SOFA scores in the placebo group at entry, likely from the small sample size, complicate efficacy and safety analyses.


    Subject Category: V. Virology including clinical and basic studies of viral infections, including hepatitis

    Pablo Vial, MD1, Francisca Valdivieso, MD2, Marcela Ferres, MD, MPH3, Raul Riquelme, MD4, M Luisa Rioseco, MD4, Mario Calvo, MD5, Constanza Castillo, MD6, Ricardo Diaz, MD7, Luis Scholz, MD8, Analia Cuiza, RN2, Edith Belmar, RN2, Carla Hernandez, RN2, Sang-Joon Lee, PhD9 and Gregory Mertz, MD9, (1)Pediatrics, University Del Desarrolo, Santiago, Chile, (2)Universidad del Desarrollo, Santiago, Chile, (3)Pediatrics, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile, (4)Hospital Regional de Puerto Montt, Puerto Montt, Chile, (5)Universidad Austral de Chile, Valdivia, Chile, (6)Universidad de la Frontera, Temuco, Chile, (7)Hospital de Los Angeles, Los Angeles, Chile, (8)Hospital Base de Osorno, Osorno, Chile, (9)Internal Medicine, University of New Mexico, Albuquerque, NM

    Disclosures:

    P. Vial, None

    F. Valdivieso, None

    M. Ferres, None

    R. Riquelme, None

    M. L. Rioseco, None

    M. Calvo, None

    C. Castillo, None

    R. Diaz, None

    L. Scholz, None

    A. Cuiza, None

    E. Belmar, None

    C. Hernandez, None

    S. J. Lee, None

    G. Mertz, None

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