CytoSorb® Usage During Valve Replacement Surgery for Infective Endocarditis Helps Stabilize Patients and May Improve Survival

10/19/2017

MONMOUTH JUNCTION, N.J., Oct. 19, 2017 — CytoSorbents Corporation (NASDAQ: CTSO), a critical care immunotherapy leader using CytoSorb® blood purification to treat deadly inflammation in critically-ill and cardiac surgery patients around the world, highlights the largest endocarditis valve replacement study using CytoSorb published to date entitled, "Hemoadsorption treatment of patients with acute infective endocarditis during surgery with cardiopulmonary bypass – a case series".

Dr. Phillip Chan, MD, PhD, Chief Executive Officer of CytoSorbents explains, "Intravenous drug abuse, dental procedures, and other infections can result in bacteria entering the bloodstream and infecting a heart valve, resulting in endocarditis. The number of cases of infective endocarditis has been rising steadily to nearly 50,000 per year in the U.S. alone, due to a near doubling of IV heroin abuse from 2006 to 2013. The trend continues to grow, driven by the widespread opioid addiction epidemic in the United States. Endocarditis is a dreaded complication that typically requires long-term antibiotics at a minimum, with approximately 25-50% of all patients eventually requiring open heart surgery to remove the infection and replace the heart valve. Certain bacterial infections and the toxins they secrete can destroy the heart valve in a matter of days and cause sepsis, leading to hemodynamic instability and an urgent need for valve replacement surgery. These patients can be very difficult to manage, with unstable blood pressure both during and after the surgery, often requiring vasopressors, extracorporeal membrane oxygenation, ventricular assist devices, or other mechanical support. The risk of complications and death, as well as costs, is also high, particularly in emergency surgeries."

In this retrospective, observational case series, Träger and colleagues document clinical outcomes in 39 consecutive patients with proven infective endocarditis undergoing valve replacement surgery in combination with intra-operative CytoSorb hemoadsorption. 59% of these cases were deemed medical emergencies, with the remainder considered "urgent". The investigators categorized patients using the predictive mortality assessment tool, EuroSCORE II (European System for Cardiac Operative Risk Evaluation II), which uses a broad set of pre-operative criteria to stratify patients on their risk of in-hospital mortality following major cardiac surgery. The higher the score, the greater the risk of death. The median EuroSCORE II was 12.8 (interquartile range 5.4-40.7) and the mean EuroSCORE II was 26.0. For those with a very high predicted mortality (EuroSCORE II = 20-40), the in-hospital mortality was 17% (1/6) and for all patients with a EuroSCORE II ≤ 40, the mortality was 7% (3/29).

These results compare favorably with mortality data from a 2016 retrospective endocarditis case series that did not use CytoSorb, entitled "EuroSCORE II underestimates mortality after cardiac surgery for infective endocarditis". In this study, Patrat-Delon and colleagues reported on the correlation of EuroSCORE II with in-hospital mortality in 149 patients with documented infective endocarditis undergoing valve replacement. In general, these patients had less severe illness where 34% were considered medical emergencies, 42% urgent, and 24% elective. In this population, the median EuroSCORE II was 9.8 (IQR 3.9-23.2) and a mean EuroSCORE II of 15.8. For patients with a EuroSCORE II = 20-40, the in-hospital mortality was 42.9% (12/28), and for all patients with a EuroSCORE II ≤ 40, the mortality was 18.0% (24/133).

Träger et al. further observed, "Treatment with the CytoSorb device was safe and well-tolerated with no device-related adverse events during or after the treatment sessions…The clinical and laboratory parameters measured along this case series revealed (i) a consistent balanced control of the inflammatory response post-operatively, shown by a marked reduction of IL-6 and IL-8 plasma levels (ii) the rapid adjustment of metabolic processes indicated by a normalization of lactate and base excess back to preoperative baseline levels within 3 days and (iii) hemodynamic stability before, during, and after the operation accompanied by a rapid decrease in need for vasopressors."

Dr. Chan commented, "Although there are clearly limitations in comparing two different retrospective, observational studies conducted at different hospitals, the magnitude of the potential protective effect of intraoperative use of CytoSorb in infective endocarditis and valve replacement surgery is intriguing. This is particularly true when accompanied by the observed improvement in perioperative hemodynamic stability, the reduction of high levels of post-operative cytokines, and the known ability of CytoSorb to directly reduce other pro-inflammatory mediators and bacterial toxins that are common in endocarditis, that could explain this improvement in mortality. Interestingly, as we observed in our REFRESH I study, valve replacement surgery is also associated with complement activation and the highest peak levels of toxic plasma free hemoglobin that are likely causing additional harm in these patients. This case series adds further credence that CytoSorb is providing positive benefit in these patients with infective endocarditis, which could be excellent news for surgeons and hospitals dealing with the costly and resource intensive medical consequences of the growing opiate epidemic."

About CytoSorbents Corporation (NASDAQ: CTSO)

CytoSorbents Corporation is a leader in critical care immunotherapy, specializing in blood purification. Its flagship product, CytoSorb® is approved in the European Union with distribution in 44 countries around the world, as a safe and effective extracorporeal cytokine adsorber, designed to reduce the "cytokine storm" or "cytokine release syndrome" that could otherwise cause massive inflammation, organ failure and death in common critical illnesses such as sepsis, burn injury, trauma, lung injury and pancreatitis, as well as in cancer immunotherapy. These are conditions where the risk of death is extremely high, yet no effective treatments exist. CytoSorb® is also being used during and after cardiac surgery to remove inflammatory mediators, such as cytokines and free hemoglobin, which can lead to post-operative complications, including multiple organ failure. CytoSorbents has completed its REFRESH (REduction in FREe Hemoglobin) 1 trial – a multi-center, randomized controlled study that has demonstrated the safety and efficacy of free hemoglobin reduction with intra-operative CytoSorb® use in a heart-lung machine during complex cardiac surgery. In 2017, the Company plans to initiate a pivotal REFRESH 2 trial intended to support U.S. FDA approval. CytoSorb® has been used safely in more than 27,000 human treatments to date.

CytoSorbents' purification technologies are based on biocompatible, highly porous polymer beads that can actively remove toxic substances from blood and other bodily fluids by pore capture and surface adsorption. Its technologies have received non-dilutive grant, contract, and other funding of approximately $20 million from DARPA, the U.S. Army, the U.S. Department of Health and Human Services, the National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), U.S. Special Operations Command (SOCOM), and others. The Company has numerous products under development based upon this unique blood purification technology, protected by 32 issued U.S. patents and multiple applications pending, including CytoSorb-XL™, HemoDefend™, VetResQ™, K+ontrol™, ContrastSorb, DrugSorb, and others.