Critical Illness: PRORATA (Procalcitonin to Reduce Antibiotic Treatments in Acutely ill patients )

Question 1

PRORATA Clinical Q

Answer 1

In critically ill ICU patients with suspected bacterial infections, what is the benefit of a procalcitonin-guided strategy on mortality and antibiotic-free days?

Question 2

PRORATA Bottom Line

Answer 2

Among critically ill patients with suspected bacterial infections, a procalcitonin-guided antibiotic strategy to treat suspected bacterial infections led to fewer days of antibiotic exposure without a >10% increase in mortality at 28 or 60 days.

Question 3

PRORATA Primary Outcome

Answer 3

Mortality at days 28 and 60 (non-inferiority analysis), and number of days without antibiotics by day 28 (superiority analysis)

Question 4

PRORATA Inclusion criteria

Answer 4

-Age ≥18 years -Suspected bacterial infection before study inclusion or sepsis during ICU stay ***If suspected bacterial infection before study inclusion, must have received no antibiotics or antibiotics for <24h

Question 5

PRORATA Interventions

Answer 5

• Randomized to procalcitonin vs. control arms
  
  • Investigators blinded to assignments before, but not after, randomization, as per open-label design
  • Procalcitonin arm: antibiotics were started or stopped based on predefined cut-off ranges of procalcitonin concentrations Starting of antibiotics discouraged if <0.5µg/L and strongly discouraged if <0.25µg/L; procalcitonin remeasured 6-12h later
  • Starting of antibiotics encouraged if ≥0.5µg/L and strongly encouraged if ≥1µg/L
  • Stopping of antibiotics encouraged if ≥80% decrease from peak concentration or absolute concentration <0.5µg/L and strongly encouraged if absolute concentration <0.25µg/L
  • Continuing of antibiotics encouraged if <80% decrease from peak concentration or absolute concentration ≥0.5µg/L and strongly encouraged if increased concentration and concentration ≥0.5µ/L
  • Control group received antibiotics according to present guidelines Physicians free to decide optimum duration of therapy based on clinical assessment Drug selection and final decision to start or stop antibiotics were ultimately at the discretion of physician in both arms.

Question 6

PRORATA Criticisms

Answer 6

• Although multicenter and randomized, design was open-label and only 8 ICUs participated.
• Surgical ICU patients represented only 10% of study population.
• Many physicians in the procalcitonin group did not follow the recommended algorithm for antibiotic discontinuation. 53% of patients randomized to procalcitonin arm did not follow the algorithm-guided treatment
• A slightly higher number of patients in the procalcitonin arm died between days 29 and 60. The analysis used a 10% margin of non-inferiority threshold for mortality. If a 5% margin of non-inferiority for mortality had been used instead, the procalcitonin arm would have had inferior mortality at 60 days.
• No formal cost-effectiveness analysis done.