Stolz 2009

Methods	Randomised clinical trial, multicentre with 7 European and US intensive care units
Participants	Inclusion criteria: VAP when intubated for > 48 h Exclusion criteria: patients were excluded it they 1) were pregnant; 2) were enrolled in another trial; 3) had received immunosuppressants or long‐term corticosteroid therapy (> 0.5 mg/kg per day for > 1 month); 4) were severely immunosuppressed, including acquired immunodeficiency syndrome; and 5) had a coexisting extrapulmonary infection diagnosed between day 1 and 3 requiring antibiotic therapy for > 3 days Included in this analysis: 101 (101) (100%)
Interventions	Guiding antibiotic decisions in VAP patients with repeated measurements Algorithm used in this study: a procalcitonin level of < 0.25 µg/L suggested the absence of VAP and discontinuation of ABs was strongly encouraged. A procalcitonin level between 0.25 µg/L and 0.5 µg/L or a decrease by ≥ 80% as compared to day 0 indicated that bacterial infection was unlikely and reduction or discontinuation of ABs was encouraged. A procalcitonin level ≥ 0.5 µg/L or decrease by < 80% as compared to day 0 was considered to indicate unresolved bacterial infection and reduction or discontinuation of AB was discouraged. A procalcitonin level of > 1 µg/L strongly suggested unresolved bacterial infection and AB discontinuation was strongly discouraged
Outcomes	Antibiotic‐free days alive Any antibiotic exposure after inclusion, i.e. total antibiotic exposure days and total antibiotic‐agent days, regardless of indication The number of mechanical ventilation‐free days The number of ICU‐free days alive The evolution of the signs and symptoms potentially linked to pulmonary infection Sa, O2, Pa, O2/Fi, O2 The evolution of the SOFA, ODIN and CPIS scores Length of hospital stay The VAP‐related clinical deterioration rate and overall mortality at 28 days
Notes	Funding: funding was granted by the Clinic of Pulmonary Medicine, University Hospital Basel. Funding obtained from Brahms AG (Hennigsdorf, Germany) Follow‐up: fixed follow‐up period of 28 days Registration: ISRCTN61015974
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Independent statistician created randomisation list
Allocation concealment (selection bias)	Low risk	Quote: "Randomisation was through arbitrary allocation to one of the two treatment assignments based on sealed, opaque envelopes. Block size was 20 envelopes. Treating physicians were not aware of envelope contents before randomisation"
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Open‐label trial where physicians knew in which group patients were and where procalcitonin levels were only communicated in the intervention arm
Blinding of outcome assessment (detection bias) All outcomes	High risk	Unblinded study member
Incomplete outcome data (attrition bias) All outcomes	Low risk	Follow‐up for mortality: 101/101 (100%)
Selective reporting (reporting bias)	Low risk	Outcomes correspond to study protocol
Other bias	Unclear risk	Adherence to procalcitonin protocol not reported/assessed

AB: antibiotic ARIs: acute respiratory infections CAP: community‐acquired pneumonia COPD: chronic obstructive pulmonary disease CPIS: Clinical Pulmonary Infection Score d: day ED: emergency department ECOPD: exacerbation of chronic obstructive pulmonary disease h: hour ICU: intensive care unit ID: identification LRTI: lower respiratory tract infection NA: not available ODIN: Organ Dysfunction and/or Infection score O_2: oxygen PaO₂/Fi: relationship between arterial oxygen tension (Pa,O2) and inspiratory oxygen fraction (FI,O2)  Pa: arterial RTI: respiratory tract infection SIRS: systemic inflammatory response syndrome SOFA: Sequential Organ Failure Assessment score VAP: ventilator‐associated pneumonia