The Randomized Controlled STRAWINSKI Trial: Procalcitonin-Guided Antibiotic Therapy after Stroke

Abstract

BackgroundPneumonia is among the most common acute complications after stroke and is associated with poor long-term outcome. Biomarkers may help identifying stroke patients at high risk for developing stroke-associated pneumonia (SAP) and to guide early treatment.AimsThis trial investigated whether procalcitonin (PCT) ultrasensitive (PCTus)-guided antibiotic treatment of SAP can improve functional outcome after stroke.MethodsIn this international, multicenter, randomized, controlled clinical trial with blinded assessment of outcomes, patients with severe ischemic stroke in the middle cerebral artery territory were randomly assigned within 40 h after symptom onset to PCTus-based antibiotic therapy guidance in addition to stroke unit care or standard stroke unit care alone. The primary endpoint was functional outcome at 3 months, defined according to the modified Rankin Scale (mRS) and dichotomized as acceptable (≤4) or unacceptable (≥5). Secondary endpoints included usage of antibiotics, infection rates, days of fever, and mortality. The trial was registered with (Identifier NCT01264549).ResultsIn the intention-to-treat-analysis based on 227 patients (112 in PCT and 115 in control group), 197 patients completed the 3-month follow-up. Adherence to PCT guidance was 65%. PCT-guided therapy did not improve functional outcome as measured by mRS (odds ratio 0.79; 95% confidence interval 0.45–1.35, p = 0.47). Pneumonia rate and mortality were similar in both groups. Days with fever tended to be lower (p = 0.055), whereas total number of days treated with antibiotics were higher (p = 0.004) in PCT compared to control group. A post hoc analysis including all PCT values in the intention-to-treat population demonstrated a significant increase on the first day of infection in patients with pneumonia and sepsis compared to patients with urinary tract infections or without infections (p < 0.0001).ConclusionPCTus-guided antibiotic therapy did not improve functional outcome at 3 months after severe ischemic stroke. PCT is a promising biomarker for early detection of pneumonia and sepsis in acute stroke patients.

Inflammatory and stress markers predicting pneumonia, outcome, and etiology in patients with stroke

“…We hereby report data on SAP and mortality prediction with CTproET and MRproANP after stroke, showing significant associations for both outcomes with both biomarkers. PCT has been associated with post-stroke infections before, 6,7 although this connection could not always be reproduced. 16 Our data confirm admission PCT values to be associated with SAP and outcome.…”

“…We deem a possible bias by this negligible, given that treatment guidance in the STRAWINSKI trial was shown not to be strongly driven by PCT, nor was there proof of efficient SAP prevention. 7 Furthermore, we only looked at the biomarker course during the first 4 days after the event, possibly explaining differences to previous reports on the same biomarkers. Although it would have been of great interest to compare these blood-borne biomarkers with imaging findings, we only had imaging data on 94 patients, details of which have been published previously.…”

“…Protocol details and primary outcome data of both studies have been previously published. 7,14,15 Briefly, both studies recruited acute ischemic stroke patients to investigate the prediction (PREDICT) and eventually procalcitonin (PCT)-guided immediate early treatment (STRA-WINSKI) of SAP. Selection criteria for PREDICT were less selective (inclusion of any ischemic stroke with a minimum NIH Stroke Scale [NIHSS] score of 1 and within 36 hours after event), leading to a larger but less severely affected cohort, whereas STRAWINSKI included patients with a minimum NIHSS score of 9 and consequently more frequent SAP.…”

“…Admission blood samples were drawn as soon as possible, but at least within 36 or 40 hours within the ischemic event in PREDICT and STRAWINSKI, respectively. 7,15,18 Biometrics Standard descriptive sum statistics were performed to describe demographics and stroke characteristics and biomarker results. We split the cohort into patients having SAP including sepsis, urinary tract infection only (UTI), and no infection (NI).…”

“…5 We hypothesized that a set of inflammatory and stress biomarkers predict SAP and functional outcome after stroke: Procalcitonin has been associated with post-stroke infections before. 6,7 Midregion pro-adrenomedullin has been previously associated with stroke-associated infections 8 and functional outcome after stroke. 9,10 Copeptin, a hypothalamic stress hormone, has been associated with higher risk of all-cause mortality, poor functional outcome after ischemic stroke, and stroke-associated infections.…”