HOspital NEtwork STudy - Preparation for a Randomized Evaluation of Anti-Pneumonia Strategies

HONEST-PREPS: Hospital Network Study - Preparation for a Randomized Evaluation of Anti-Pneumonia Strategies

Hospital Acquired and Ventilator Associated Pneumonia (HAP/VAP) pose a significant burden to patients admitted to the Intensive Care Unit (ICU). Reported incidence ranges from 10-16% in all ICU patients (including HAP and VAP) and around 20-30% in ventilated patients (VAP). Patients with HAP/VAP have a high mortality rate. The estimated attributable mortality of VAP is 6-13%.

Randomized Controlled Trials (RCTs) are the gold standard for evaluating medical interventions, but are difficult to perform in this population. Several preventive and therapeutic treatment options are being developed that will require evaluation in phase-III trials. These trials are challenging due to the relatively low incidence of the outcome (e.g. HAP/VAP) or of the domain under study (e.g. specific antibiotic resistant infections) and the requirement of informed consent in critically ill patients. There is a need for a well-organized and well-trained international RCT network that enables efficient execution of a series of RCTs in this population.

The aim of the current study is to set up an infrastructure to prospectively enroll patients at risk of HAP/VAP in ICUs in several European countries. Site personnel will be trained to obtain a GCP (Good Clinical Practice) certification (if not already done), to timely identify and enroll patients at risk of HAP/VAP, to timely identify occurrence of HAP/VAP, collect informed consent forms, collect source data, enter data into a clinical database, and use a dedicated system to reply to queries. Site sample collection, processing, identifying the causative organism, and antibiotic susceptibility testing will be validated and adapted if required where possible. Where site infrastructure and regulations allow, the possibility of automated data collection of included participants will be explored to ensure sustainability of the future platform. Furthermore, collected data will be used to inform future diagnostic, preventive and therapeutic trials. E.g. they may support assumptions in sample size calculations and expected number of enrolled participants, they may help in prioritizing interventions, or they may be used in simulations of adaptive trials to optimize decision rules.

Inclusion Criteria:

• Age >= 18 years

• At risk of acquiring bacterial HAP or VAP during ICU stay, defined as meeting all of the following criteria:

  • expected or documented hospital length of stay of more than 48 hours
  • admitted to the ICU

Exclusion Criteria:

• Death is deemed to be imminent or inevitable during this hospital admission AND one or more of the patient, substitute decision maker or attending physician are not committed to full active treatment