PRINCETON, N.J., Oct. 12, 2022 /PRNewswire/ — CytoSorbents Corporation (NASDAQ: CTSO), a leader in the treatment of life-threatening conditions in the intensive care unit and cardiac surgery using blood purification via its proprietary polymer adsorption technology, announced the presentation of exciting new data on the use of CytoSorb® in various cardiac surgery indications at the 36th European Association for Cardio-Thoracic Surgery (EACTS) Annual Meeting last week in Milan, Italy.
During the main scientific session, Professor Matthias Thielmann – Dept. of Thoracic and Cardiovascular Surgery, West-German Heart & Vascular Center, University Duisburg-Essen, Germany presented the “Effect of intraoperative hemoadsorption therapy in acute infective endocarditis with confirmed Staph. aureus bacteremia.“
The incidence of infective endocarditis, or infection of a heart valve, is increasing globally. Staphylococcal aureus endocarditis (SAE) accounts for roughly a quarter to a third of all cases and is a dreaded complication associated with intravenous drug abuse and use of dirty needles, hospital-acquired infections, prosthetic heart valves, and community acquired endocarditis. Importantly, SAE is the most aggressive form of valvular infection and can lead to a myriad of complications including rapid destruction of the valve, heart failure, cytokine storm, florid septic shock, septic embolization, and the highest mortality risk among all types of infective endocarditis, even with surgical replacement of the heart valve. CytoSorb is used in this patient population during open heart surgery to control cytokine storm, reduce inflammation and Staphylococcal toxins, and reverse shock.
- Study population: 130 consecutive patients with confirmed SAE who underwent heart valve surgery at 2 leading German Heart Centers between 01/2015 – 03/2022. Mean age (60.8 vs. 60.7, p=ns) and baseline risk according to EuroScore II (12.0 vs. 11.9, p=ns) were nearly identical in the two groups. Approximately 25% of patients had a repeat cardiac operation while almost 20% were IV drug users.
- Study objectives: To compare clinical outcomes between patients who underwent standard of care valve replacement surgery (Control group; n=55) and patients who underwent standard of care valve replacement surgery plus intraoperative hemoadsorption (HA) with CytoSorb (n=75).
- Primary outcome: Postoperative vasopressor requirements assessed by the Vasoactive-Inotropic Score (a well-established and accepted measure of vasopressor support required to manage hemodynamic instability) was significantly reduced in the CytoSorb group at 6, 12, 24, 48 and 72 hours (p<0.02 for all), consistent with improved hemodynamic stability after surgery
- Secondary outcomes: Sepsis-related mortality was significantly reduced in the CytoSorb group (8.0% vs. 21.8%, p=0.02), as was overall 30-day (17.3% vs. 32.7%, p=0.03) and 90-day mortality (21.3% vs. 40%, p=0.03). This marked effect on mortality translated into a Number Needed to Treat (NNT) of just 5 patients to save a life.
The authors summarized the results as: “1) Mortality following cardiac surgery in infective endocarditis, particularly caused by S. aureus, is still high; 2) Intraoperative cytokine adsorption leads to improved postoperative hemodynamics, 3) Improved survival in patients treated by intraoperative adjunctive hemoadsorption” and concluded that: “Hemoadsorption with CytoSorb seems to be a safe and effective adjunctive therapy in Staphylococcus aureus infective endocarditis during cardiac surgery.“
Dr. Daniel Wendt, Vice President – Medical Affairs Cardiovascular at CytoSorbents, stated, “The selection of this study for presentation in the main scientific program highlights the importance of these findings. As these results clearly demonstrate, CytoSorb can address some of the biggest management challenges in these very high risk endocarditis patients.”
CytoSorbents also hosted a lunch symposium entitled, “Hemoadsorption with CytoSorb in high-risk cardiac surgery indications – new data” that drew approximately 150 attendees and was chaired by Professors Christophe Baufreton (Angers, France) and Piotr Suwalski (Warsaw, Poland). Key presentations included:
“Clinical benefits in patients undergoing heart transplantation – results of a single center RCT.” Dr. Endre Németh (Budapest, Hungary) presented the results of the first ever randomized, controlled trial (RCT) using CytoSorb intraoperatively during cardiac transplantation.
- Study population: 55 patients were randomized 1:1 to either standard of care (SOC) or SOC plus CytoSorb. Baseline characteristics were well-balanced between the two groups, including mean recipient age of 56 years in both arms and donor heart age of approximately 10 years less. Approximately half of the patients suffered from idiopathic cardiomyopathy and approximately one third from ischemic cardiomyopathy. Both cardiopulmonary bypass duration (SOC 129 [104-169] vs. SOC + CytoSorb 133 [116-165] minutes, p=ns) and total ischemic time (SOC 173±41 vs. SOC + CytoSorb 152±45 minutes, p=ns) were similar.
- Primary outcome: Need for vasopressors to support blood pressure as measured by the Vasoactive Inotropic Score (VIS) was significantly reduced by CytoSorb (p=0.046), driven by reductions in both noradrenaline and vasopressin requirements. Importantly, this resulted in significantly lower rates of vasoplegia or vasodilatory shock (SOC 48% vs. SOC + CytoSorb 20%; 58% relative risk reduction (RRR), p=0.028) and shorter overall duration of vasopressor support (p=0.046).
- Secondary outcomes: All clinical secondary endpoints evaluated in the trial were either similar between the two groups or statistically superior with SOC + CytoSorb including less time on mechanical ventilation (SOC 65 [23-287] vs. 25 [19-68.8] hours, p=0.025), lower rates of postoperative acute kidney injury (SOC 76% vs. SOC + CytoSorb 36.7%; RRR 52%, p=0.004) and fewer days in the ICU (SOC 12 [8.5-18] vs. 8.5 [8-10.3] days, p=0.022). Importantly, there were no differences in all rejection markers evaluated at 30 days, while there were 2 deaths in the SOC group and no deaths in the CytoSorb group.
Based on these RCT data, the authors concluded that proactive intraoperative CytoSorb use in patients undergoing heart transplantation resulted in important improvements in clinical and economic outcomes, including: 1) Significantly improved postoperative hemodynamic stability with reduced severity and duration of vasoplegia, 2) Significantly lower rates of postoperative acute kidney injury, 3) Significantly shorter time on postop mechanical ventilation, and 4) Significant reduction in ICU stay.
“Removal of antithrombotic drugs to reduce bleeding complications and costs in high urgency operations.” Professor Michael Schmoeckel (Hamburg, Germany) presented previously published data demonstrating significant bleeding reductions with the intraoperative use of CytoSorb for antithrombotic drug removal in 55 patients undergoing urgent coronary artery bypass grafting (CABG) and 21 patients undergoing urgent type A aortic dissection repair who were either on ticagrelor or rivaroxaban at the Asklepios St. Georg Klinik in Hamburg, Germany
- Key Outcomes: Among CABG patients, the use of CytoSorb was associated with significant reductions in 24-hour chest tube drainage (relative risk reduction [RRR] 60%; p=0.004), platelet (RRR 67%; p=0.048) and red blood cell transfusions (RRR 67; p=0.012) and need for re-operation (RRR 100%; p=0.0003). Total operative time was also significantly reduced (RRR 15%; p=0.004) and patients who underwent antithrombotic removal with CytoSorb spent 2 fewer days in the ICU (RRR: 50%; p=0.014) and 5 fewer days overall in the hospital (RRR 31%; p=0.024). Similar types and magnitude of benefits were also observed in patients undergoing antithrombotic removal during aortic dissection surgery, but due to the smaller sample size, statistical significance was only achieved for reduction in 24-hour chest tube drainage (RRR 47%, p<0.001) and platelet transfusions (RRR 31%, p=0.049).
- Cost Benefit: A boot strap analysis on the 55 CABG patients, investigating the budget impact of CytoSorb use for antithrombotic removal, demonstrated CytoSorb to be a dominant therapy resulting in both clinical benefit and also substantial cost-savings. Specifically, each use of CytoSorb was associated with median budget savings of approximately € 4,200 (including the cost of the device), driven primarily by less operative time and shorter ICU stays.
“CytoSorb in infective endocarditis patients – what can we learn from recent data?” Professor Matthias Thielmann (Essen, Germany) followed his presentation in the main scientific session of the conference by providing a summary of recently published data from different studies at the West German Heart & Vascular Center, highlighting the use of CytoSorb in cardiac surgery applications to mitigate the harmful effects of surgery.
- Publication on “Intraoperative hemoadsorption in patients with native mitral valve infective endocarditis” in 58 consecutive patients (CytoSorb, n=30; Control, n=28) showed that CytoSorb led to a significant reduction in the need for vasopressors, a reduced incidence of postoperative sepsis (Control 39.2% vs CytoSorb 16.7%, p=0.05), and a significant reduction in sepsis-related mortality (Control 18% vs CytoSorb 0%, p=0.02) in this well-defined population.
- Publication on “Extracorporeal cytokine adsorption: Significant reduction of catecholamine requirement in patients with AKI and septic shock after cardiac surgery” detailed a case series of 98 high-risk cardiac surgery patients who developed postoperative acute kidney injury and sepsis, and were treated by postoperative continuous renal replacement therapy (CRRT) plus 15 hours of adjunctive hemoadsorption with CytoSorb. In this trial, that involved the Department of Nephrology at the University of Essen in a team-based, patient-centric approach, patients demonstrated a rapid and significant decrease of lactate levels and vasopressor support.
- Publication on “Intraoperative hemoadsorption in high-risk patients with infective endocarditis” evaluated a series of 70 high-risk patients undergoing cardiac surgery for infective endocarditis. In a propensity-score matched comparison (35 vs. 35 patients), the SOFA-score normalized significantly faster over a 7-day period in the CytoSorb treated group, among other benefits.
Professor Thielmann then commented on the results of the REMOVE endocarditis trial and compared them to the latest data from the University of Nuremberg and Essen and concluded that patient selection in infective endocarditis is crucial, especially since high-risk patients, such as those with SAE, are likely to benefit most from adjunctive hemoadsorption techniques. Professor Thielmann concluded by stating that CytoSorb is the only new concept in the surgical treatment of infective endocarditis in many years, and has been used routinely for this indication at his institution.
Dr. Wendt added, “I was delighted to attend the annual EACTS meeting in person this year and was impressed by my discussions with so many highly-motivated and experienced cardiac surgeons and intensivists from all over the world who are using CytoSorb during and after cardiothoracic surgery. From Hamburg to Madrid, Budapest to Rome, and Warsaw to Paris, clinical adoption of CytoSorb is rapidly increasing as cardiac surgeons recognize the significant benefits of using hemoadsorption in their most challenging cases. With more data coming from multiple investigator-initiated trials, as well as our own company-sponsored studies, we anticipate that this momentum will only grow stronger in the future. As a busy academic cardiac surgeon, I had the opportunity to use CytoSorb in my most challenging cases for many years and witnessed first-hand its value in my practice. In my current role, my top priority is to make our key enabling technology the new standard in cardiac surgery around the world.”
Dr. Efthymios Deliargyris, Chief Medical Officer of CytoSorbents concluded, “The new data presented at this year’s EACTS conference validate our conviction that our proprietary hemoadsorption therapy is a “game-changing” intervention in cardiac surgery. The clinical benefits ranging from reversing shock and stabilizing patients postoperatively, to shorter ICU stays for heart transplant patients, to significantly less bleeding in patients on antithrombotic drugs undergoing high risk surgery, to reductions in mortality in the sickest endocarditis patients, speak to the power of our technology. These data support a robust clinical and economic value proposition that directly translates to significantly better outcomes and cost savings to heart centers around the world. We remain laser-focused on our clinical efforts to continue generating high quality evidence in cardiac surgery and are committed to making our technology available to U.S. centers with the execution of our currently ongoing pivotal STAR-T and STAR-D trials under FDA Breakthrough Device Designation.”
CytoSorbents Corporation is a leader in the treatment of life-threatening conditions in the intensive care unit and in cardiac surgery through blood purification. Its lead product, CytoSorb®, is approved in the European Union and distributed in 75 countries worldwide. It is an extracorporeal cytokine adsorber that reduces “cytokine storm” or “cytokine release syndrome” in common critical illnesses that can lead to massive inflammation, organ failure and patient death. In these diseases, the risk of death can be extremely high, and there are few, if any, effective treatments. CytoSorb is also used during and after cardiothoracic surgery to remove inflammatory mediators that can lead to postoperative complications, including multiple organ failure. As of June 30, 2022, more than 179,000 CytoSorb devices have been used cumulatively. CytoSorb was originally launched in the European Union under CE mark as the first cytokine adsorber. Additional CE mark extensions were granted for bilirubin and myoglobin removal in clinical conditions such as liver disease and trauma, respectively, and for ticagrelor and rivaroxaban removal in cardiothoracic surgery procedures. CytoSorb has also received FDA Emergency Use Authorization in the United States for use in adult critically ill COVID-19 patients with impending or confirmed respiratory failure. The DrugSorb™-ATR antithrombotic removal system, based on the same polymer technology as CytoSorb, also received two FDA Breakthrough Device Designations, one for the removal of ticagrelor and another for the removal of the direct oral anticoagulants (DOAC) apixaban and rivaroxaban in a cardiopulmonary bypass circuit during urgent cardiothoracic procedures. The company has initiated two FDA-approved pivotal studies to support FDA marketing approval of DrugSorb-ATR in the United States. The first is the randomized, controlled STAR-T (Safe and Timely Antithrombotic Removal-Ticagrelor) study of 120 patients at 30 centers to evaluate whether intraoperative use of DrugSorb-ATR can reduce the perioperative risk of bleeding in patients receiving ticagrelor and undergoing cardiothoracic surgery. The second study is the STAR‑D (Safe and Timely Antithrombotic Removal-Direct Oral Anticoagulants) randomized, controlled trial of 120 patients at 30 centers evaluating the intraoperative use of DrugSorb-ATR to reduce perioperative bleeding risk in patients undergoing cardiothoracic surgery and taking direct oral anticoagulants, including apixaban and rivaroxaban.
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 $48 million from DARPA, the U.S. Department of Health and Human Services (HHS), the National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), the U.S. Army, the U.S. Air Force, U.S. Special Operations Command (SOCOM), Air Force Material Command (USAF/AFMC), and others. The Company has numerous marketed products and products under development based upon this unique blood purification technology protected by many issued U.S. and international patents and registered trademarks, and multiple patent applications pending, including ECOS-300CY®, CytoSorb-XL™, HemoDefend-RBC™, HemoDefend-BGA™, VetResQ®, K+ontrol™, DrugSorb™, DrugSorb™-ATR, ContrastSorb, and others. For more information, please visit the Company’s websites at www.cytosorbents.com and www.cytosorb.com or follow us on Facebook and Twitter.
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