공시 • Mar 24
Spectral Medical and Vantive Announce Publication of Complete Results from Spectral’S Tigris Trial in the Lancet Respiratory Medicine
Spectral Medical Inc. and Vantive announced the publication of the complete results from the Tigris trial in The Lancet Respiratory Medicine. The randomized-controlled trial evaluated the use of Polymyxin B Hemoadsorption (PMX) in adults with endotoxic septic shock, providing a more complete picture of patient outcomes, including survival and safety over time. Each year, approximately 5-7 million cases of endotoxic septic shock, a particularly deadly form of sepsis, occur worldwide. The published Tigris trial results confirm the positive primary and key secondary endpoints previously reported in August 2025 and provide additional analyses on longer term survival, safety, and treatment effect. After adjusting for baseline severity, the Tigris trial demonstrated an absolute risk reduction for mortality of 10.3% at 28 days corresponding to a number needed to treat (NNT) to prevent one death of 9.7 and 15.5% at 90-days corresponding to a NNT of 6.5. The Tigris trial was a U.S.-based, multicenter, Phase 3 study evaluating PMX in adults with endotoxic septic shock (ESS), defined by an Endotoxin Activity Assay (EAA) level between 0.60 and 0.90. EAA is an FDA cleared, semiquantitative diagnostic test for measurement of endotoxin activity, allowing for rapid measurements to obtain results in approximately 30 minutes. Eligible patients also had to meet additional criteria for ESS including multiple organ dysfunction; a Multiple Organ Dysfunction Score (MODS) >9 or a Sequential Organ Failure Assessment (SOFA) score of >11. A total of 157 patients were randomized in a 2:1 ratio to receive either PMX plus standard care (n=106) or standard care alone (n=51). The prespecified primary analysis used a Bayesian statistical model, which evaluates results in the context of prior data—in this case a subgroup of the prior EUPHRATES trial. The Tigris trial’s design and analysis plan were aligned with published FDA’s Guidance for the Use of Bayesian Statistics in Medical Device Clinical Trials. The Tigris trial publication appears in The Lancet Respiratory Medicine. The publication includes extensive supplementary analyses, including Kaplan-Meier survival curves, subgroup analyses, and Bayesian sensitivity analyses, providing a comprehensive evaluation of treatment effect across multiple statistical assumptions. The publication confirms the previously reported positive findings for the primary and key secondary endpoints announced in August 2025, while providing additional analyses on survival, safety, secondary and sensitivity analyses. Intention to treat cohort showed a probability of benefit of 95.3% at 28 days. Adjusted odds ratio 0.67 [0.39-1.08]. Adjusted probability of benefit from PMX at 28 days exceeds the prespecified 95% target and thus meets the prespecified primary endpoint. Adjusted absolute risk reduction for mortality was 10.3% [-1.7, 22.3] corresponding to a number needed to treat (NNT) to save one life at 28 days of 9.7. The key secondary endpoint, mortality at 90 days, showed a 99.4% probability of benefit for patients treated with PMX. Adjusted odds ratio 0.54 [0.32-0.87]. Adjusted absolute risk reduction in mortality was 15.5% [3.6, 27.1] corresponding to a number needed to treat (NNT) to save one life at 90 days of 6.5. 90-day results were robust to all sensitivity analyses and show > 98% probability for benefit at 90 days even for Tigris alone (non-informative prior). Survival over 90 days was significantly greater for patients treated with PMX with a posterior hazard ratio: 0.68 [0.47, 0.95]; probability of benefit 98.8%. At day 28, nearly half of surviving patients remained hospitalized (46%) and 16% remained in the ICU, reflecting the ongoing clinical instability typical of septic shock patients. By day 90, however, nearly all surviving patients (98%) had been discharged from hospital. Kaplan-Meier survival curves demonstrated continued separation beyond day 28, indicating that the survival benefit observed with PMX was sustained over time. Adverse events over the treatment period did not differ between PMX and standard of care. A serious adverse event (SAE) occurred in 30 subjects (30%) randomized to PMX and in 11 (22%) randomized to SOC, a difference which is not statistically significant. Two subjects (2%) experienced a SAE that was classified as possibly, probably or definitely related to the intervention (PMX, catheter or anticoagulation). Neither was permanent and both subjects were discharged from the hospital. This safety profile for PMX is consistent with other forms of extracorporeal blood purification therapies commonly used in the ICU, including ICU dialysis. The Tigris manuscript will be presented during the Late-Breaking Studies Affecting Patient Outcomes session at the Society of Critical Care Medicine (SCCM) Critical Care Congress. The presentation will take place in Skyline Ballroom, of the McCormick Place convention center in Chicago IL at 10:20AM local time. Publication of the Tigris results represents an important milestone in advancing the clinical evidence supporting endotoxin-targeted therapy in septic shock. Spectral Medical intends to submit the final Premarket Approval (PMA) module (Module 3) for PMX to the FDA around the end of April to mid-May 2026. If approved by the FDA, Vantive plans to commercialize both EAA and PMX, beginning in the United States, to support Targeted Rapid Endotoxin Adsorption (TREA) Therapy. PMX is not approved for use in the United States. EAA Rx Only: For safe and proper use of devices mentioned herein, please refer to User Manual. The full manuscript is now available online in The Lancet Respiratory Medicine.
