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

Abstract

Background: Pneumonia 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.

Aims: This trial investigated whether procalcitonin (PCT) ultrasensitive (PCTus)-guided antibiotic treatment of SAP can improve functional outcome after stroke.

Methods: In 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 http://ClinicalTrials.gov (Identifier NCT01264549).

Results: In 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).

Conclusion: PCTus-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.

Keywords: antibiotic prophylaxis; biomarker-guided treatment; infections; outcome; pneumonia; procalcitonin; stroke.

Figures

Figure 1

Trial profile.

Figure 2

Distribution of modified Rankin Scale (mRS) scores 3 months after stroke onset. Percentage of respective scores in the guidance [procalcitonin (PCT)] group and control group (STD) in the intention-to-treat analysis. Scores on the scale range from 0 to 6, with 0 indicating no symptoms and 6 indicating death.

Figure 3

Three-month survival in the intention-to-treat population. PCT, PCT group; STD, control group. In the PCT group, 81 of 106 patients survived 90 days after stroke onset, whereas in the STD group, 89 of 108 patients survived.

Figure 4

Days with fever and antibiotic treatment within the first 7 days after stroke onset. Proportion of patients with 0, 1, 2, 3, 4, 5, 6, or 7 days of (A) fever defined by body temperature ≥37.5°C and (B) antibiotic treatment in the guidance [procalcitonin (PCT)] group and control group (STD) of the intention-to-treat (ITT) population.

Figure 5

Procalcitonin (PCT) in different types of poststroke infections. (A) PCT values of the first day of urinary tract infection (UTI) only or stroke-associated pneumonia (SAP) were compared to all PCT values obtained within the first 7 days after stroke onset from patients before infection was diagnosed or without any infection. The red line indicates the cut-off for the PCT concentration of 0.05 ng/ml. (B) PCT values of the first 7 days were compared between patients diagnosed for UTI only, SAP, and for patients without any diagnosed infection. Analyses are based on the intention-to-treat group.