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

Study Overview
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Brief Summary
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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.

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

Conditions
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Hospital-acquired Pneumonia, Ventilator Associated Pneumonia

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the quality and efficiency of a research platform for HAP/VAP in ICUs by measuring the timeliness of enrolling eligible patients. | Assess the proportion of screened, eligible patients at risk of developing HAP or VAP by being enrolled within 48 hours of ICU admission. | Through study completion, an average of 2 years | 
| To determine the quality and efficiency of a research platform for HAP/VAP in ICUs by capturing bacterial HAP/VAP episodes. | Analyse the proportion of enrolled patients who develop HAP/VAP during the initial ICU admission and who are registered in the eCRF (electronic Case Report Form) within 24 hours after onset. Onset is defined as the time of X-ray showing an infiltrate confirming HAP/VAP for patients meeting HAP/VAP FDA criteria. | Through study completion, an average of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the incidence of HAP/VAP at the ICU. | -Incidence of HAP and VAP per 1,000 patient-days | From the date of enrolment through to the date of ICU discharge, an average of 11 days | 
| To determine the implementation of infection prevention and control measures in routine ICU care for prevention of HAP/VAP. | -Implementation of ICU-level HAP/VAP infection prevention measures | From the date of enrolment through to the date of ICU discharge, an average of 11 days | 
| To determine microbiological etiology of HAP/VAP at the ICU (1). | -Microbiological cure between 7 and 10 days after HAP/VAP onset (%). (Proportion of patients with positive HAP/VAP diagnosis with the resolution of the symptoms between day 7-10 after the onset) | Between days 7 and 10 after HAP/VAP onset | 
| To determine microbiological etiology of HAP/VAP at the ICU (2). | -Distribution of bacterial pathogens (%). (Proportion of identified bacterial pathogens associated with HAP/VAP episode). | +/- 48 hours of HAP/VAP onset | 
| To determine microbiological etiology of HAP/VAP at the ICU (3) | -Resistance profiles of bacterial pathogens (% resistant) (proportion of resistant bacterial pathogen associated with HAP/VAP episode). | +/- 48 hours of HAP/VAP onset | 
| To determine management of HAP/VAP at the ICU (1) | -IMV (Invasive Mechanical Ventilation)-free-days up to 28 days after VAP onset (days). | From the date of enrolment through to the date of ICU discharge, on average of 6 days | 
| To determine management of HAP/VAP at the ICU (2) | -Antibiotic consumption before and after HAP/VAP (type of antibiotic administered per patient). | From the date of enrolment through to the date of ICU discharge, on average of 11 days | 
| To determine management of HAP/VAP at the ICU (3). | -Survival up to 90 days post HAP/VAP onset rate (%) (Proportion of patient's confirmed alive vs. dead in %) | 90 days after HAP/VAP onset | 
| To determine outcome of HAP/VAP at the ICU (1). | -ICU survival rate (%). (Proportion of patients discharged from ICU alive vs. patients with in-ICU death) | From the date of HAP/VAP onset through to the date of ICU discharge, on average of 11 days | 
| To determine outcome of HAP/VAP at the ICU (2). | -Hospital survival rate (%). (Proportion of patients discharged from hospital alive vs. patients with in-hospital death) | From the date of HAP/VAP onset through to the date of hospital discharge, on average of 12 days | 
| To determine outcome of HAP/VAP at the ICU (3). | -Length of ICU stay before and after HAP/VAP (number of days spent in ICU before and after HAP/VAP onset) | From the date of enrolment through to the date of ICU discharge, on average of 11 days | 
| To determine outcome of HAP/VAP at the ICU (4). | -Length of hospital stay before and after HAP/VAP (number of days spent in hospital before and after HAP/VAP onset). | From the date of enrolment through to the date of hospital discharge, on average of 12 days |