The Preventive Antibiotics in Stroke Study (PASS): a pragmatic randomised open-label masked endpoint clinical trial

Westendorp, Willeke F.; Vermeij, Jan-Dirk; Zock, Elles; Hooijenga, Imke; Kruyt, Nyika D.; Bosboom, Hans J L W; Kwa, Vincent I H; Weisfelt, Martijn; Remmers, Michel J M; Houten, R. ten; Schreuder, Antonia H. C. M. L.; Vermeer, Sarah E.; Dijk, Ewout J. van; Dippel, Diederik W.J.; Dijkgraaf, Marcel G. W.; Spanjaard, Lodewijk; Vermeulen, M.; Poll, Tom van der; Prins, Jan M.; Vermeij, Frédérique H; Roos, Yvo B.W.E.M.; Kleyweg, R. P.; Kerkhoff, Henk; Brouwer, Matthijs C.; Zwinderman, Aeilko H.; Beek, Diederik van de; Nederkoorn, Paul J.

doi:10.1016/s0140-6736(14)62456-9

Cited by 274 publications

(319 citation statements)

References 22 publications

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“…This sympathetically mediated immunodepression likely contributes to an increase in the risk of poststroke infection [6]. Poststroke infection, primarily pneumonia, is independently associated with increased morbidity and mortality [7,8].…”

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confidence: 99%

Stroke, Inflammation and the Immune Response: Dawn of a New Era

Becker

Buckwalter

2016

Neurotherapeutics

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confidence: 99%

Stroke, Inflammation and the Immune Response: Dawn of a New Era

Becker

Buckwalter

2016

Neurotherapeutics

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“…In contrast to this assumption, many studies included patients with very mild stroke. In the largest study, the PASS trial [3], a NIHSS score of 1 was sufficient to be included in the study, for example. As a consequence, the overall median NIHSS in this study was only 5, indicating that the majority of study participants suffered from mild stroke.…”

Section: Discussionmentioning

confidence: 99%

“…Following theoretical considerations, it may not be wise to use fluoroquinolones with glutaminergic effects such as ciprofloxacine or levofloxacine as first-line drugs in patients with acute stroke. Some antibiotics, in particular minocycline [55,56], and also β-lactam antibiotics such as ceftriaxone, used in the PASS trial [3], may exert neuroprotective properties [66,67]. Although the rate of complications from antibiotic drug therapy was almost negligible in most studies, the choice of antibiotic drug influences unwanted side effects from treatment.…”

Section: Discussionmentioning

confidence: 99%

“…The BPreventive Antibiotics in Stroke Study^(PASS) was a well-designed, large multicenter study conducted in 30 stroke units in the Netherlands [3]. Over a 4-year period, 2550 patients were assigned to prophylactic Ceftriaxone or treatment as usual.…”

Section: Clinical Studies On Preventive Antibiotic Therapy After Strokementioning

confidence: 99%

“…After several clinical studies performed during the last 10 years have produced negative or inconclusive results, however, the enthusiasm for prophylactic antibiotic therapy in acute stroke has now plummeted considerably. After the negative results of 2 large clinical trials-the STROKE-INF [2] and PASS [3] trials published in 2015-an editorial commentator mused that the concept of preventive antibiotic therapy after stroke may have utterly BPASSed away^ [4].…”

Section: Introductionmentioning

confidence: 99%

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Prophylactic Antibiotic Therapy for Preventing Poststroke Infection

Schwarz

2016

Neurotherapeutics

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Infections, in particular pneumonia, are common complications in patients with acute stroke and are associated with a less favorable neurologic and functional outcome. Patients with severe stroke and dysphagia are at highest risk of infection. Experimental and clinical data suggest stroke-induced immunodeficiency as a major factor contributing to the high incidence of infection after stroke. Preclinical studies support the potential benefit of preventive antibiotic therapy in acute stroke for lowering the incidence of infection and improving clinical outcome. Several smaller clinical trials on preventive antibiotic therapy in patients with stroke conducted during the last 10 years yielded inconclusive results. Recently, 2 large, open-label, controlled trials failed to demonstrate an improved clinical outcome after preventive antibiotic therapy in patients with acute stroke treated in specialized stroke units. In the BPreventive Antibiotics in Stroke Study^, antibiotic therapy lowered the rate of infection but did not influence outcome. In the STROKE-INF study, performed in patients with dysphagia after stroke, antibiotic therapy did not lower the incidence of pneumonia and had no prognostic significance. At present, preventive antibiotic therapy cannot be recommended as a therapeutic option for acute stroke.

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Effect of Routine Low-Dose Oxygen Supplementation on Death and Disability in Adults With Acute Stroke

Roffe

Nevatte

Sim

et al. 2017

JAMA

160

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IMPORTANCE Hypoxia is common in the first few days after acute stroke, is frequently intermittent, and is often undetected. Oxygen supplementation could prevent hypoxia and secondary neurological deterioration and thus has the potential to improve recovery. OBJECTIVE To assess whether routine prophylactic low-dose oxygen therapy was more effective than control oxygen administration in reducing death and disability at 90 days, and if so, whether oxygen given at night only, when hypoxia is most frequent, and oxygen administration is least likely to interfere with rehabilitation, was more effective than continuous supplementation. DESIGN, SETTING, AND PARTICIPANTSIn this single-blind randomized clinical trial, 8003 adults with acute stroke were enrolled from 136 participating centers in the United Kingdom within 24 hours of hospital admission if they had no clear indications for or contraindications to oxygen treatment (first patient enrolled April 24, 2008; last follow-up January 27, 2015).INTERVENTIONS Participants were randomized 1:1:1 to continuous oxygen for 72 hours (n = 2668), nocturnal oxygen (21:00 to 07:00 hours) for 3 nights (n = 2667), or control (oxygen only if clinically indicated; n = 2668). Oxygen was given via nasal tubes at 3 L/min if baseline oxygen saturation was 93% or less and at 2 L/min if oxygen saturation was greater than 93%. MAIN OUTCOMES AND MEASURESThe primary outcome was reported using the modified Rankin Scale score (disability range, 0 [no symptoms] to 6 [death]; minimum clinically important difference, 1 point), assessed at 90 days by postal questionnaire (participant aware, assessor blinded). The modified Rankin Scale score was analyzed by ordinal logistic regression, which yields a common odds ratio (OR) for a change from one disability level to the next better (lower) level; OR greater than 1.00 indicates improvement.RESULTS A total of 8003 patients (4398 (55%) men; mean [SD] age, 72 [13] years; median National Institutes of Health Stroke Scale score, 5; mean baseline oxygen saturation, 96.6%) were enrolled. The primary outcome was available for 7677 (96%) participants. The unadjusted OR for a better outcome (calculated via ordinal logistic regression) was 0.97 (95% CI, 0.89 to 1.05; P = .47) for oxygen vs control, and the OR was 1.03 (95% CI, 0.93 to 1.13; P = .61) for continuous vs nocturnal oxygen. No subgroup could be identified that benefited from oxygen. At least 1 serious adverse event occurred in 348 (13.0%) participants in the continuous oxygen group, 294 (11.0%) in the nocturnal group, and 322 (12.1%) in the control group. No significant harms were identified.CONCLUSIONS AND RELEVANCE Among nonhypoxic patients with acute stroke, the prophylactic use of low-dose oxygen supplementation did not reduce death or disability at 3 months. These findings do not support low-dose oxygen in this setting.

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The Preventive Antibiotics in Stroke Study (PASS): a pragmatic randomised open-label masked endpoint clinical trial

Cited by 274 publications

References 22 publications

Stroke, Inflammation and the Immune Response: Dawn of a New Era

Stroke, Inflammation and the Immune Response: Dawn of a New Era

Prophylactic Antibiotic Therapy for Preventing Poststroke Infection

Effect of Routine Low-Dose Oxygen Supplementation on Death and Disability in Adults With Acute Stroke

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