The use of extracorporeal blood purification therapies (EBPT) is becoming increasingly
widespread worldwide in everyday clinical practice, particularly in the critical care
setting. For most of these treatments, the extracorporeal removal of inflammatory
mediators (via enhanced transmembrane clearance and/or selective/un-selective adsorption
of bacterial toxins or inflammatory mediators) is already well established in the
literature. Unselective cytokine removal is the main rationale for the use of EBPT, and
it might explain the effect of these treatments on multiorgan dysfunction in critically
ill patients. Indeed, an increment in hemodynamic stability and an improvement in the
multiorgan dysfunction scoring system of treated patients are consistently observed in
most of the studies available in the literature. Nonetheless, most of the clinical trials
aimed at exploring the effect of EBPT on patients' long-term outcomes have failed to
demonstrate consistent results regarding 28 day- or hospital- mortality rates.
Interestingly, the post-hoc analysis of large databases suggests that a specific
subpopulation of patients, who are likely to benefit more than others from EBPT, could be
identified in clinical practice. As an example, press releases from the Euphrates trial
suggest that a specific range of baseline endotoxin activity assay might correlate with a
positive long-term outcome in patients treated with Toraymixin cartridges. Nowadays, a
personalized approach to extracorporeal therapy has been advocated as the only strategy
capable of maximizing the clinical effect of EBPT and their impact on patient outcomes
(i.e. precision medicine).
The identification of clinical characteristics correlated with positive outcomes during
EBPT allows the implementation of specifically designed trials, focused on a well-defined
cluster of patients.
The implementation of a large database encompassing the clinical/biochemical
characteristics of patients undergoing EBPT is thus widely hoped for to enable the
identification of a cluster of patients with specific features who most benefit from
these treatments.
Although it is well known that only a clinical trial can formally assess the effect of
EBPT on a specific clinical outcome, several drawbacks pose practical limitations to the
implementation of a clinical trial in the critical care setting for this purpose. First,
most European countries (and particularly Italy) do not allow the enrollment and
randomization of non-competent patients (as critically ill patients formally are), due to
ethical issues. Second, clinical trials are associated with very high costs. Third, the
quality of results and conclusions deriving from post-hoc analysis of randomized clinical
trials (often underpowered) may be qualitatively similar to those obtained from a very
large database of patients observed during treatments performed according to the routine
clinical practice.
As an example, COMPACT and COMPACT 2 trials, failed to demonstrate a significant effect
of Coupled plasma-filtration adsorption (CPFA) on the outcome of critically ill septic
patients, with the notable exception of specific subpopulations (e.g. those where an
adequate volume of plasma was filtered and adsorbed). This conclusion was obtained
through two highly-costly multicenter randomized clinical trials, prematurely halted due
to ethical issues, using post-hoc analysis of a subgroup of an already limited sample
size.
Nowadays, the identification of specific clusters of patients during EBPT is obtained by
means of the implementation of a large web-based registry where a network of researchers
can upload the clinical data of patients undergoing EBPT in line with the routine
clinical practice of each single center. Taking into consideration the feasibility of the
research (i.e. mainly related with the lack of critical ethical issues and the
easy-to-use interface of web-platforms), these observation-based registries are
inexpensive and effective tools able to identify specific clusters of patients within a
very large sample size with widely heterogeneous clinical characteristics.
As an example, a web-based registry has been already implemented to describe the clinical
effects of polymyxin-B based cartridges for endotoxin removal (EUPHAS 2 registry).
Another one has been similarly implemented to describe the clinical effects of
un-selective cytokine adsorption obtained with CytoSorb (CytoSorb registry).
Taking into consideration the fact that data on CPFA already exist and web-based
registries are already available for aforementioned membranes, the aim of this project is
to design and nationally promote a web-based registry designed for all remaining
commercial membranes. In particular, an easy-to-use web-based platform will be made
available for all centers that spontaneously adhere to this project.
Three main characteristics will distinguish this web-based registry when compared with
the already available Euphas 2 and CytoSorb registries. First, it will also be available
for smartphone and/or tablet applications; this characteristic will guarantee easy-to-use
access and data uploading and enhanced compliance from clinical researchers. Second, it
will not be confined to a simplistic registration of patients' data; it will instead also
provide the clinician with clinical tools that might be helpful for patient management
(e.g. automatic calculation of clinical scoring systems, ideal body weight, functions of
mechanical ventilation, antibiotic adjustment according to renal function, etc.). All
these tools will provide the clinician with real-time feedback; this web-based registry
will provide a clear example of translational medicine and translational research, where
data from clinical practice will feed a database for clinical research and,
contemporaneously, the research tool will improve clinical practice, providing useful
instruments for routine practice. Finally, this web-based registry will allow every
center to instantaneously evaluate its results, providing a real-time basic statistic for
every recorded variable (e.g. age at enrollment, main comorbidities, baseline serum
creatinine, mortality rate, rate of multidrug resistant bacteria, etc.). This function
may allow each center to continuously monitor outcomes and local practices, and will
represent a major improvement when compared to already existing platforms in Italy, such
as the Prosafe.
With this rationale, the research questions are:
is there a cluster of critically ill patients that mostly benefits from
extracorporeal blood purification therapies (EBPT) with specific membrane?
might some baseline variables be used to identify this subpopulation of "responsive"
patients? In particular, may these indicators be employed to guide indications for
EBPT , in order to personalize treatments and improve patients' long-term outcome?