TY - JOUR
T1 - The Preventive Antibiotics in Stroke Study (PASS): a pragmatic randomised open-label masked endpoint clinical trial
AU - Westendorp, Willeke F.
AU - Vermeij, Jan-Dirk
AU - Zock, Elles
AU - Hooijenga, Imke J.
AU - Kruyt, Nyika D.
AU - Bosboom, Hans J. L. W.
AU - Kwa, Vincent I. H.
AU - Weisfelt, Martijn
AU - Remmers, Michel J. M.
AU - ten Houten, Robert
AU - Schreuder, A. H. C. M. Tobien
AU - Vermeer, Sarah E.
AU - van Dijk, Ewout J.
AU - Dippel, Diederik W. J.
AU - Dijkgraaf, Marcel G. W.
AU - Spanjaard, Lodewijk
AU - Vermeulen, Marinus
AU - van der Poll, Tom
AU - Prins, Jan M.
AU - Vermeij, Frederique H.
AU - Roos, Yvo B. W. E. M.
AU - Kleyweg, Ruud P.
AU - Kerkhoff, Henk
AU - Brouwer, Matthijs C.
AU - Zwinderman, Aeilko H.
AU - van de Beek, Diederik
AU - Nederkoorn, Paul J.
AU - AUTHOR GROUP
AU - Vermeij, J.-D.
AU - Kerkhoff, H.
AU - Bosboom, J. L. W.
AU - Kwa, V. I. H.
AU - Weisfelt, M.
AU - Remmers, M. J. M.
AU - van Dijk, E. J.
AU - Vermeij, F.
AU - Schreuder, A.
AU - Vermeer, S. E.
AU - ten Houten, R.
AU - Dippel, D. W. J.
AU - Kappelle, L. J.
AU - van der Worp, H. B.
AU - Merkies, I. S. J.
AU - de Bruijn, S. F. T. M.
AU - de Laat, K. F.
AU - Haag, Den
AU - Jellema, K.
AU - Keizer, K.
AU - de Rijk, M. C.
AU - Vermeij, A. J.
AU - de Gans, K.
PY - 2015
Y1 - 2015
N2 - In adults with acute stroke, infections occur commonly and are associated with an unfavourable functional outcome. In the Preventive Antibiotics in Stroke Study (PASS) we aimed to establish whether or not preventive antimicrobial therapy with a third-generation cephalosporin, ceftriaxone, improves functional outcome in patients with acute stroke. In this multicentre, randomised, open-label trial with masked endpoint assessment, patients with acute stroke were randomly assigned to intravenous ceftriaxone at a dose of 2 g, given every 24 h intravenously for 4 days, in addition to stroke unit care, or standard stroke unit care without preventive antimicrobial therapy; assignments were made within 24 h after symptom onset. The primary endpoint was functional outcome at 3 months, defined according to the modified Rankin Scale and analysed by intention to treat. The primary analysis was by ordinal regression of the primary outcome. Secondary outcomes included death, infection rates, antimicrobial use, and length of hospital stay. Participants and caregivers were aware of treatment allocation but assessors of outcome were masked to group assignment. This trial is registered with controlled-trials.com, number ISRCTN66140176. Between July 6, 2010, and March 23, 2014, a total of 2550 patients from 30 sites in the Netherlands, including academic and non-academic medical centres, were randomly assigned to the two treatment groups: 1275 patients to ceftriaxone and 1275 patients to standard treatment (control group). 12 patients (seven in the ceftriaxone group and five in the control group) withdrew consent immediately after randomisation, leaving 2538 patients available for the intention-to-treat-analysis (1268 in the ceftriaxone group and 1270 in the control group). 2514 (99%) of 2538 patients (1257 in each group) completed 3-month follow-up. Preventive ceftriaxone did not affect the distribution of functional outcome scores on the modified Rankin Scale at 3 months (adjusted common odds ratio 0·95 [95% CI 0·82-1·09], p=0·46). Preventive ceftriaxone did not result in an increased occurrence of adverse events. Overgrowth infection with Clostridium difficile occurred in two patients ( <1%) in the ceftriaxone group and none in the control group. Preventive ceftriaxone does not improve functional outcome at 3 months in adults with acute stroke. The results of our trial do not support the use of preventive antibiotics in adults with acute stroke. Netherlands Organization for Health Research and Development, Netherlands Heart Foundation, and the European Research Council
AB - In adults with acute stroke, infections occur commonly and are associated with an unfavourable functional outcome. In the Preventive Antibiotics in Stroke Study (PASS) we aimed to establish whether or not preventive antimicrobial therapy with a third-generation cephalosporin, ceftriaxone, improves functional outcome in patients with acute stroke. In this multicentre, randomised, open-label trial with masked endpoint assessment, patients with acute stroke were randomly assigned to intravenous ceftriaxone at a dose of 2 g, given every 24 h intravenously for 4 days, in addition to stroke unit care, or standard stroke unit care without preventive antimicrobial therapy; assignments were made within 24 h after symptom onset. The primary endpoint was functional outcome at 3 months, defined according to the modified Rankin Scale and analysed by intention to treat. The primary analysis was by ordinal regression of the primary outcome. Secondary outcomes included death, infection rates, antimicrobial use, and length of hospital stay. Participants and caregivers were aware of treatment allocation but assessors of outcome were masked to group assignment. This trial is registered with controlled-trials.com, number ISRCTN66140176. Between July 6, 2010, and March 23, 2014, a total of 2550 patients from 30 sites in the Netherlands, including academic and non-academic medical centres, were randomly assigned to the two treatment groups: 1275 patients to ceftriaxone and 1275 patients to standard treatment (control group). 12 patients (seven in the ceftriaxone group and five in the control group) withdrew consent immediately after randomisation, leaving 2538 patients available for the intention-to-treat-analysis (1268 in the ceftriaxone group and 1270 in the control group). 2514 (99%) of 2538 patients (1257 in each group) completed 3-month follow-up. Preventive ceftriaxone did not affect the distribution of functional outcome scores on the modified Rankin Scale at 3 months (adjusted common odds ratio 0·95 [95% CI 0·82-1·09], p=0·46). Preventive ceftriaxone did not result in an increased occurrence of adverse events. Overgrowth infection with Clostridium difficile occurred in two patients ( <1%) in the ceftriaxone group and none in the control group. Preventive ceftriaxone does not improve functional outcome at 3 months in adults with acute stroke. The results of our trial do not support the use of preventive antibiotics in adults with acute stroke. Netherlands Organization for Health Research and Development, Netherlands Heart Foundation, and the European Research Council
U2 - https://doi.org/10.1016/S0140-6736(14)62456-9
DO - https://doi.org/10.1016/S0140-6736(14)62456-9
M3 - Article
C2 - 25612858
SN - 0140-6736
VL - 385
SP - 1519
EP - 1526
JO - Lancet
JF - Lancet
IS - 9977
ER -