Clinical trial NCT00472667: PROcalcitonin Reduce Antibiotic Treatments in Acute-Ill Patients (PRORATA)
Official title: Impact of Procalcitonin to Reduce Antibiotics Use in ICU Adults Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Bacterial Infections
Keywords: Bacterial infections
Procalcitonin
Intensive care unit
Antibiotic therapy
Suspicion of bacterial infection or proven
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2007-05-14
Enrollment: 630
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: DIAGNOSTIC

Brief summary: The study is a prospective, randomized, controlled intervention trial conducted in 9 centers, comparing a conventional strategy versus a PCT-guided strategy to start or to discontinue antibiotics, in patients with suspected community or hospital- acquired infection.

Detailed description: Clinical and laboratory signs are neither specific nor sensitive for diagnosis of sepsis in critically-ill patients. Because delaying antimicrobial therapy may be deleterious, broad-spectrum antibiotics are widely used in ICU -patients, even when they are not needed. In addition, only few well-designed studies concerning the duration of antibiotic treatment have been so far published. Consequently, many patients received antibiotics during the ICU stay. Many studies have shown that exposure to antibiotics, the so called "selection pressure" is an independent risk factor for acquisition of resistance in individual patients. Therefore, reducing antibiotic use is probably necessary to control antibiotic resistance. Many clinical studies have shown that procalcitonin (PCT) is able to distinguish the inflammatory response to infection from other types of inflammation and to distinguish bacterial from viral infections. Recent studies have shown that PCT guidance substantially and safely reduced antibiotic overuse in patients with lower respiratory tract infections. We aimed to evaluate the role of PCT in reducing the use of antibiotics in ICU adult patients. The study is a prospective, randomized, controlled intervention trial conducted in 9 centers, comparing a conventional strategy versus a PCT-guided strategy to start or to discontinue antibiotics, in patients with suspected community or hospital- acquired infection.

Eligibility criteria: Inclusion Criteria:

* Patient hospitalised in the ICU
* Bacterial infection suspected
* At ICU admission the patient do not receive antibiotics or receive antibiotics for less than 24hours and an interval between admission and inclusion \< 12 hours
* During ICU stay, provided that the interval between the start of suspected infection and inclusion is \< 12hours
* Written inform consent from the patient or relatives. The consent may be obtained after the enrollment if the patient is not able to give consent and if there is no relatives

Exclusion Criteria:

* Age \< 18 years
* Pregnancy
* Patient expected to remain hospitalised in the ICU for less than 3 days
* Neutropenia
* Infection or presumed infection requiring prolonged antibiotic therapy (endocarditis,osteo-articular infection, mediastinitis, deep abscess, tuberculosis, pneumocystis pneumonia, toxoplasmosis).
* Simplified Acute Physiology Score II at ICU admission (calculated during the first 12h)
* Attending physician declining to use full life support.

Primary outcomes:
measure: Exposition to antibiotics, defined by antibiotic-free days
timeFrame: assessed 28 days after inclusion
measure: Mortality
timeFrame: at Day 28 and Day 60
Secondary outcomes:
measure: Consumption of antibiotics expressed as the Defined Daily Dose/1000 ICU-days
timeFrame: between D1 and D28
measure: The length of ICU and hospital stay
timeFrame: during the stay at the hospital
measure: The evolution of SOFA score parameters
timeFrame: between D1 and D28
measure: The number of mechanical ventilation-free days
timeFrame: at D28
measure: The acquisition cost of antibiotics
timeFrame: between D1 and D28
measure: The percentage of emerging multiresistant bacteria between D1 and D28, as assessed by microbiologic examination of all clinical samples.
timeFrame: between D1 and D28
measure: The percentages of relapses of infection
timeFrame: between D1 and D28
Other outcomes:
Locations:
city: Paris
country: France
facility: Chu Bichat Claude Bernard
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Lila BOUADMA, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C, Schortgen F, Lasocki S, Veber B, Dehoux M, Bernard M, Pasquet B, Regnier B, Brun-Buisson C, Chastre J, Wolff M; PRORATA trial group. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet. 2010 Feb 6;375(9713):463-74. doi: 10.1016/S0140-6736(09)61879-1. Epub 2010 Jan 25.