Clinical trial NCT04580680: Extracorporeal Blood Purification Therapy in Critically Ill Patients (GlobalARRT)
Official title: Extracorporeal Blood Purification Therapy in Critically Ill Patients: an Interactive,Web-based,Multicenter,Observational Prospective Registry
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Critical Illness
Acute Kidney Injury
Sepsis
Systemic Inflammatory Response Syndrome
Lead sponsor: Careggi Hospital
Sponsor class: OTHER
Collaborators: name: University of Florence
First posted: 2020-10-08
Enrollment: 1000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All medical institutions that provide EBP treatments to critically ill patients are eligible for participation.

Brief summary: Worldwide, the use of Extracorporeal Blood Purification (EBP) in everyday clinical practice is becoming increasingly common, particularly in critical care settings. The efficacy of most of these treatments on removal of inflammatory mediators is the main rationale behind the use of EBP in critically ill patients with multiorgan dysfunction. Nonetheless, there are still some doubts as to the clinical efficacy of bacterial toxins and cytokines removal and many clinical trials aiming at exploring the effect of EBP on long-term outcomes of septic patients have failed to demonstrate consistent results regarding 28 day- or hospital-mortality rates. The primary aim of this observational prospective web-based registry is to define the possible clusters of critically ill patients - treated with extracorporeal blood purification therapies worldwide - who are homogeneous regarding both clinical and treatment characteristics and seem to benefit the most from EBP.

Detailed description: Since May 2019, our research group has developed, implemented, and nationally spread the "ARRT registry" with the aim to describe the subpopulations of critically ill patients that benefit the most from EBP therapy with oXiris (6). The project is currently ongoing, involving more than 50 centers in Italy, with data from more than 65 patients treated with oXiris. Differently from other registries, the ARRT registry runs on a web-based platform easily accessible from internet-based technologies, including smartphones, that offers a user-friendly approach, facilitates data uploading, and enhances research collaboration. Furthermore, it adopts a proactive approach, in the sense that it includes several automatic calculators and decision support tools that might help clinicians to personalize treatments directly at the bedside (e.g. automatic calculation of clinical scoring systems, ideal body weight, mechanical ventilation setting, antibiotic adjustment according to renal function, etc.). All these tools can provide the clinician with real-time feedbacks. This web-based registry provides a clear example of translational medicine and translational research where data from clinical practice feed a database for clinical research and, contemporaneously, the database research tools improve clinical practice. Finally, this web-based registry allows each participating center to instantaneously evaluate its own data and obtain real-time basic statistics for each recorded variable (e.g. age at enrollment, main comorbidities, baseline serum creatinine, mortality rate, rate of multidrug-resistant bacteria, etc.), thus allowing for continuous monitoring of outcomes and local practices.

Overall, these features may prove particularly useful during treatment of critically ill septic patients with multiorgan dysfunction. Recently, the COVID-19 pandemic has been characterized by high prevalence of patients with severe multiorgan dysfunction, high mortality rate, lack of ICU resources, and the need for ICU discharge in a rapid, but safe, manner. The association between acute kidney injury and COVID-19 infection is well established. Organ crosstalk and systemic inflammation are the most accredited causes of Acute Kidney Injury (AKI) in these patients. Several EBP therapies have been proposed to attenuate systemic inflammation and/or support renal function in COVID-19 patients. Nevertheless, no data is currently available on application and feasibility of EBP therapies in COVID-19 patients or on their outcomes. Notably, the ARRT registry was able to effectively capture clinical data on systemic inflammation, organ dysfunction, and outcomes in patients treated with oXiris during the COVID-19 pandemic in Italy. In this regard, the implementation of a similar registry at the global level might prove effective for supporting clinicians involved in the treatment of patients with COVID-19 infection and multiorgan dysfunction worldwide.

Eligibility criteria: Inclusion Criteria: patients who meet all the following inclusion criteria may be included in this study:

1. Admission to ICU
2. Indications for at least one of the following extracorporeal blood purification treatments:

   1. Continuous Renal Replacement Therapy (CRRT) / Intermittent Hemodialysis (IHD) / Hybrid therapies for renal support/replacement;
   2. Immunomodulation therapy in critically ill patients using hemodiafilters with larger pore sizes characterized by enhanced transmembrane clearance of larger molecules (such as cytokines), hemodiafilters with enhanced unselective absorption of cytokines and/or endotoxins, cartridges with enhanced absorption of cytokines and/or endotoxins, techniques aimed at improving extracorporeal removal of cytokines and/or endotoxins.

It should be underlined that the lack of established guidelines on the use of membranes for extracorporeal blood purification (and on RRTs in general) leads to variability in clinical practice and treatments are initiated in accordance with the judgement of the responsible physician. Under these circumstances, it is preferable to keep inclusion criteria as wide as possible so as to obtain a real picture of clinical practice worldwide.

Exclusion Criteria: besides contraindications to the use of the EBP adopted (as from the manual of instructions), there are no exclusion criteria.

Primary outcomes:
measure: Define the possible clusters of critically ill patients
timeFrame: 10 days after Extracorporeal Blood Purification Therapy (EBPT) initiation
Secondary outcomes:
measure: To assess the correlation between cluster membership and positive short-term outcome.
timeFrame: 48 hours after EBPT initiation
measure: To assess the correlation between cluster membership and positive long-term outcome.
timeFrame: 10 days after EBPT initiation
measure: To assess the correlation between positive short-term outcome and changes from baseline.
timeFrame: 24 hours after EBPT initiation
measure: To describe the clinical circumstances under which clinicians opt for specific techniques of extracorporeal blood purification therapy worldwide.
timeFrame: 10 days after EBPT initiation
measure: To describe the clinical circumstances under which clinicians opt for specific techniques of extracorporeal blood purification therapy worldwide in terms of absolute and relative frequencies of clinical variables.
timeFrame: 10 days after EBPT initiation
measure: To describe EBP utilization rates in intensive care units worldwide.
timeFrame: 10 days after EBPT initiation
measure: To describe EBP utilization rates in intensive care units worldwide in terms of absolute frequency
timeFrame: 10 days after EBPT initiation
measure: To describe EBP in terms of relative frequencies for treatment type in intensive care units worldwide.
timeFrame: 10 days after EBPT initiation
measure: To describe EBP in terms of technical characteristics in intensive care units worldwide.
timeFrame: 10 days after EBPT initiation
measure: To describe EBP in terms of average flow rates in intensive care units worldwide.
timeFrame: 10 days after EBPT initiation
Other outcomes:
Locations:
city: Florence
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi
Study officials:
affiliation: University of Florence, Florence, Italy
name: Gianluca Villa, md
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cruz DN, Antonelli M, Fumagalli R, Foltran F, Brienza N, Donati A, Malcangi V, Petrini F, Volta G, Bobbio Pallavicini FM, Rottoli F, Giunta F, Ronco C. Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA. 2009 Jun 17;301(23):2445-52. doi: 10.1001/jama.2009.856.
citation: Klein DJ, Foster D, Schorr CA, Kazempour K, Walker PM, Dellinger RP. The EUPHRATES trial (Evaluating the Use of Polymyxin B Hemoperfusion in a Randomized controlled trial of Adults Treated for Endotoxemia and Septic shock): study protocol for a randomized controlled trial. Trials. 2014 Jun 11;15:218. doi: 10.1186/1745-6215-15-218.
citation: Payen DM, Guilhot J, Launey Y, Lukaszewicz AC, Kaaki M, Veber B, Pottecher J, Joannes-Boyau O, Martin-Lefevre L, Jabaudon M, Mimoz O, Coudroy R, Ferrandiere M, Kipnis E, Vela C, Chevallier S, Mallat J, Robert R; ABDOMIX Group. Early use of polymyxin B hemoperfusion in patients with septic shock due to peritonitis: a multicenter randomized control trial. Intensive Care Med. 2015 Jun;41(6):975-84. doi: 10.1007/s00134-015-3751-z. Epub 2015 Apr 11.
citation: Cutuli SL, Artigas A, Fumagalli R, Monti G, Ranieri VM, Ronco C, Antonelli M; EUPHAS 2 Collaborative Group. Polymyxin-B hemoperfusion in septic patients: analysis of a multicenter registry. Ann Intensive Care. 2016 Dec;6(1):77. doi: 10.1186/s13613-016-0178-9. Epub 2016 Aug 8.
citation: Friesecke S, Trager K, Schittek GA, Molnar Z, Bach F, Kogelmann K, Bogdanski R, Weyland A, Nierhaus A, Nestler F, Olboeter D, Tomescu D, Jacob D, Haake H, Grigoryev E, Nitsch M, Baumann A, Quintel M, Schott M, Kielstein JT, Meier-Hellmann A, Born F, Schumacher U, Singer M, Kellum J, Brunkhorst FM. International registry on the use of the CytoSorb(R) adsorber in ICU patients : Study protocol and preliminary results. Med Klin Intensivmed Notfmed. 2019 Nov;114(8):699-707. doi: 10.1007/s00063-017-0342-5. Epub 2017 Sep 4.
citation: Villa G, De Rosa S, Samoni S, Neri M, Cosimo C, Romagnoli S, Gavagni M, Ronco C, De Gaudio AR. oXirisNet Registry: A Prospective, National Registry on the oXiris Membrane. Blood Purif. 2019 Apr 11;47 Suppl 3:1-8. doi: 10.1159/000499356. Online ahead of print.