Simvastatin in the acute respiratory distress syndrome
Daniel F McAuley, John G Laffey, Cecilia M O'Kane, Gavin D Perkins, Brian Mullan, T John Trinder, Paul Johnston, Philip A Hopkins, Andrew J Johnston, Cliona McDowell, Christine McNally, HARP-2 Investigators, Irish Critical Care Trials Group, Andrew J Johnston, Archana Paikray, Cat Yates, Petra Polgarova, Esther Price, Amy McInerney, Katarzyna Zamoscik, Ged Dempsey, Colette Seasman, Lynn Gilfeather, Noel Hemmings, Sinead O'Kane, Paul Johnston, Lukas Pokorny, Chris Nutt, Orla O'Neill, Prashast Prashast, Chris Smalley, Reni Jacob, James O'Rourke, Syed Farjad Sultan, Carole Schilling, Gavin D Perkins, Teresa Melody, Keith Couper, Ron Daniels, Fang Gao, Julian Hull, Timothy Gould, Matthew Thomas, Katie Sweet, Dorothy Breen, Emer Neau, Willis J Peel, Catherine Jardine, Paul Jefferson, Stephen E Wright, Kayla Harris, Matthew Thomas, Sarah Hierons, John Laffey, Michael Scully, Veronica McInerney, Rola Jafaar, Luigi Camporota, Katie Lei, Sundeep Kaul, Molly Chivburi, Andrew Gratix, Rachael Bennett, Victoria Martinson, Lisa Sleight, Neil Smith, Philip A Hopkins, Daniel Hadfield, Sarah Casboult, Fiona Wade-Smith, Julie Dawson, Clare Mellis, Clair Harris, Georgina Parsons, Sinead Helyar, Andrew R Bodenham, Stuart Elliott, Zoe Beardow, Sian Birch, Brian Marsh, Teresa Martin, Akesh Dhrampal, Melissa Rosbergen, Stephen Webb, Fiona Bottrill, Henrik Reschreiter, Helena Barcraft-Barnes, Julie Camsooksai, Andrew Johnston, Aisling Clarkson, Conor Bentley, Lauren Cooper, Yongyan Qui, Natalie Mitchell, Ronald Carrera, Arlo Whitehouse, Christopher M Danbury, Nicola Jacques, Abby Brown, David Rogerson, Craig Morris, Timothy Walsh, Mike Gillies, Grant Price, Kallirroi Kefala, Neil Young, David Hope, Corrienne McCulloch, Jean Antonelli, Pam Ramsay, Kirsty Everingham, Louise Boardman, Heidi Dawson, Fiona Pollock, Joanne Thompson, Ingeborg D Welters, Lee Poole, Peter Hampshire, Alison Hall, Karen Williams, Anna Walker, Laura Youds, Samantha Hendry, Victoria Waugh, Julie Patrick-Heselton, David Shaw, Irfan Chaudry, Jacqueline Baldwin, Stephen Drage, Laura Ortiz-Ruiz de Gordoa, Daniel McAuley, Brian Mullan, Leona Bannon, Vanessa Quinn, Lia McNamee, Griania White, Margaret McFarland, Brian Wells, Maurizio Cecconi, Johannes Mellinghoff, Donal Ryan, Alistair Nichol, Banwari Agarwal, Paula Meale, Sarah James, Kulwant Dhadwal, Daniel Martin, Agnieszka Walecka, Stephen Ward, John Trinder, Samantha Hagan, Janice Montgomery, Catherine Leonard, Elizabeth Lemon, Tom Trinick, Murthy Buddhavarapu, Geraldine Ward, Christopher Bassford, Alan Davidson, Kate McGuigan, Anissa Benchiheub, Naomi Hickey, Alexander Binning, Steven Henderson, J A Wood, Andrew J Burtenshaw, Dawn Kelly, Terry Martin, Jessica Thrush, Julie Wollaston, Stephen Graystone, Gavin Nicol, Gareth Sellors, Duncan Young, Rupert Pearse, Kathy Rowan, Barry Williams, Daniel McAuley, John Laffey, Lynn Murphy, Geoff Bellingan, David Harrison, Anthony Gordon, Daniel F McAuley, John G Laffey, Cecilia M O'Kane, Gavin D Perkins, Brian Mullan, T John Trinder, Paul Johnston, Philip A Hopkins, Andrew J Johnston, Cliona McDowell, Christine McNally, HARP-2 Investigators, Irish Critical Care Trials Group, Andrew J Johnston, Archana Paikray, Cat Yates, Petra Polgarova, Esther Price, Amy McInerney, Katarzyna Zamoscik, Ged Dempsey, Colette Seasman, Lynn Gilfeather, Noel Hemmings, Sinead O'Kane, Paul Johnston, Lukas Pokorny, Chris Nutt, Orla O'Neill, Prashast Prashast, Chris Smalley, Reni Jacob, James O'Rourke, Syed Farjad Sultan, Carole Schilling, Gavin D Perkins, Teresa Melody, Keith Couper, Ron Daniels, Fang Gao, Julian Hull, Timothy Gould, Matthew Thomas, Katie Sweet, Dorothy Breen, Emer Neau, Willis J Peel, Catherine Jardine, Paul Jefferson, Stephen E Wright, Kayla Harris, Matthew Thomas, Sarah Hierons, John Laffey, Michael Scully, Veronica McInerney, Rola Jafaar, Luigi Camporota, Katie Lei, Sundeep Kaul, Molly Chivburi, Andrew Gratix, Rachael Bennett, Victoria Martinson, Lisa Sleight, Neil Smith, Philip A Hopkins, Daniel Hadfield, Sarah Casboult, Fiona Wade-Smith, Julie Dawson, Clare Mellis, Clair Harris, Georgina Parsons, Sinead Helyar, Andrew R Bodenham, Stuart Elliott, Zoe Beardow, Sian Birch, Brian Marsh, Teresa Martin, Akesh Dhrampal, Melissa Rosbergen, Stephen Webb, Fiona Bottrill, Henrik Reschreiter, Helena Barcraft-Barnes, Julie Camsooksai, Andrew Johnston, Aisling Clarkson, Conor Bentley, Lauren Cooper, Yongyan Qui, Natalie Mitchell, Ronald Carrera, Arlo Whitehouse, Christopher M Danbury, Nicola Jacques, Abby Brown, David Rogerson, Craig Morris, Timothy Walsh, Mike Gillies, Grant Price, Kallirroi Kefala, Neil Young, David Hope, Corrienne McCulloch, Jean Antonelli, Pam Ramsay, Kirsty Everingham, Louise Boardman, Heidi Dawson, Fiona Pollock, Joanne Thompson, Ingeborg D Welters, Lee Poole, Peter Hampshire, Alison Hall, Karen Williams, Anna Walker, Laura Youds, Samantha Hendry, Victoria Waugh, Julie Patrick-Heselton, David Shaw, Irfan Chaudry, Jacqueline Baldwin, Stephen Drage, Laura Ortiz-Ruiz de Gordoa, Daniel McAuley, Brian Mullan, Leona Bannon, Vanessa Quinn, Lia McNamee, Griania White, Margaret McFarland, Brian Wells, Maurizio Cecconi, Johannes Mellinghoff, Donal Ryan, Alistair Nichol, Banwari Agarwal, Paula Meale, Sarah James, Kulwant Dhadwal, Daniel Martin, Agnieszka Walecka, Stephen Ward, John Trinder, Samantha Hagan, Janice Montgomery, Catherine Leonard, Elizabeth Lemon, Tom Trinick, Murthy Buddhavarapu, Geraldine Ward, Christopher Bassford, Alan Davidson, Kate McGuigan, Anissa Benchiheub, Naomi Hickey, Alexander Binning, Steven Henderson, J A Wood, Andrew J Burtenshaw, Dawn Kelly, Terry Martin, Jessica Thrush, Julie Wollaston, Stephen Graystone, Gavin Nicol, Gareth Sellors, Duncan Young, Rupert Pearse, Kathy Rowan, Barry Williams, Daniel McAuley, John Laffey, Lynn Murphy, Geoff Bellingan, David Harrison, Anthony Gordon
Abstract
Background: Studies in animals and in vitro and phase 2 studies in humans suggest that statins may be beneficial in the treatment of the acute respiratory distress syndrome (ARDS). This study tested the hypothesis that treatment with simvastatin would improve clinical outcomes in patients with ARDS.
Methods: In this multicenter, double-blind clinical trial, we randomly assigned (in a 1:1 ratio) patients with an onset of ARDS within the previous 48 hours to receive enteral simvastatin at a dose of 80 mg or placebo once daily for a maximum of 28 days. The primary outcome was the number of ventilator-free days to day 28. Secondary outcomes included the number of days free of nonpulmonary organ failure to day 28, mortality at 28 days, and safety.
Results: The study recruited 540 patients, with 259 patients assigned to simvastatin and 281 to placebo. The groups were well matched with respect to demographic and baseline physiological variables. There was no significant difference between the study groups in the mean (±SD) number of ventilator-free days (12.6±9.9 with simvastatin and 11.5±10.4 with placebo, P=0.21) or days free of nonpulmonary organ failure (19.4±11.1 and 17.8±11.7, respectively; P=0.11) or in mortality at 28 days (22.0% and 26.8%, respectively; P=0.23). There was no significant difference between the two groups in the incidence of serious adverse events related to the study drug.
Conclusions: Simvastatin therapy, although safe and associated with minimal adverse effects, did not improve clinical outcomes in patients with ARDS. (Funded by the U.K. National Institute for Health Research Efficacy and Mechanism Evaluation Programme and others; HARP-2 Current Controlled Trials number, ISRCTN88244364.).
Source: PubMed