PMX Hemoperfusion for Septic Shock
(TIGRIS Trial)
Recruiting in Palo Alto (17 mi)
+19 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Spectral Diagnostics (US) Inc.
Must be taking: Vasopressors, Antibiotics
Disqualifiers: End-stage renal disease, Severe heart failure, Recent AMI, others
No Placebo Group
Approved in 4 jurisdictions
Trial Summary
What is the purpose of this trial?This trial tests whether adding a blood-filtering device called the PMX cartridge to regular treatment helps patients with severe infections and organ failure. The device aims to remove harmful toxins from their blood.
Do I have to stop taking my current medications for the trial?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.
What data supports the effectiveness of the drug Polymyxin B for treating infections?
Research shows that Polymyxin B is effective against various bacteria, including methicillin-resistant Staphylococcus and some multidrug-resistant Gram-negative bacteria, which suggests it could be useful in treating infections caused by these organisms.
12345Is PMX Hemoperfusion with Polymyxin B safe for humans?
Polymyxin B has been used safely in various forms, including topical applications and intravenous treatments, for infections caused by resistant bacteria. It is generally well tolerated, but there can be side effects like nephrotoxicity (kidney damage) with improper use. Studies suggest that newer derivatives like SPR741 have reduced kidney toxicity and are well tolerated in healthy subjects.
678910How is PMX hemoperfusion treatment different from other treatments for septic shock?
PMX hemoperfusion is unique because it uses a special cartridge to remove endotoxins (harmful substances from bacteria) from the blood, which can help stabilize blood circulation and improve organ function in septic shock patients. This approach is different from standard treatments that typically focus on antibiotics and supportive care, as it directly targets the toxins contributing to the condition.
1112131415Eligibility Criteria
Adults with endotoxemic septic shock who have low platelet counts, reduced urine output despite fluids, need vasopressors to maintain blood pressure, and are suspected or confirmed to have an infection. They must also show signs of organ dysfunction and not be on chronic dialysis or suffering from conditions like severe heart failure, recent heart attack, uncontrolled bleeding, major trauma within the last 36 hours, extreme white cell or platelet depletion.Inclusion Criteria
I am on a high dose of Phenylephrine.
I am taking vasopressin with another blood pressure medication.
I've received a fluid boost of at least 30mL/kg in the last day.
+14 more
Exclusion Criteria
Any other condition, that in the opinion of the investigator, would preclude the subject from being a suitable candidate for enrollment, such as end-stage chronic illness (eg. lack of source control and bowel necrosis) with no reasonable expectation of survival to hospital discharge
Major trauma within 36 hours of screening
Inability to obtain an informed consent from the subject, family member or an authorized surrogate
+19 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1-2 weeks
Treatment
Participants receive the PMX cartridge treatment twice, approximately 24 hours apart, in addition to standard medical care
3 days
2 treatment sessions (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment, with follow-up visits or calls to determine mortality status
12 months
Follow-up at Day 28, Day 90, and 12 months
Participant Groups
The trial is testing the safety and effectiveness of adding a Polymyxin B Hemoperfusion (PMX) cartridge treatment to standard care for patients with endotoxemic septic shock compared to standard care alone. It's a prospective study involving multiple centers where participants are randomly assigned to one of the two groups.
2Treatment groups
Experimental Treatment
Active Control
Group I: PMX TreatmentExperimental Treatment1 Intervention
Standard medical care for septic shock plus treatment with the PMX cartridge (twice approximately 24 hours apart)
Group II: ControlActive Control1 Intervention
Standard medical care alone
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Baystate Medical CenterSpringfield, MA
CHI MemorialChattanooga, TN
UPMCPittsburgh, PA
Mt Sinai HospitalNew York, NY
More Trial Locations
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Who Is Running the Clinical Trial?
Spectral Diagnostics (US) Inc.Lead Sponsor
References
Comparison of antibacterial activities of polymyxin B and colistin against multidrug resistant Gram negative bacteria. [2020]Background: Polymyxin B and colistin have similar structures except for one amino acid. Usually, physicians choose either polymyxin B or colistin for treatment of infections caused by multidrug-resistant (MDR) organisms. The preference is based on previous experience. Not much data are found in the literature comparing the two drugs against the same microorganisms. In this study, we compared in vitro antimicrobial activities of the two polymyxins against a panel of highly resistant and susceptible microorganisms. Methods: Eighty-nine clinical isolates (27 Klebsiella pneumoniae, 31 Acinetobacter baumannii and 31 Pseudomonas aeruginosa) were tested in broth microdilution assays. Time-kill curve experiments were carried out on selected isolates. Results: Significantly lower MICs for polymyxin B than for colistin were found against all species tested including K. pneumoniae (p < .02), A. baumannii (p < .001) and P. aeruginosa (p < .01). The low MICs caused a change in categorical interpretations of only two K. pneumoniae and two P. aeruginosa. Similar results were obtained in time-kill curve experiments with both susceptible and resistant clinical isolates. Conclusions: Significantly lower MICs were found for polymyxin B against three of the most critical MDR species. Even though differences in categorical interpretations were not striking, lower MICs might be a critical consideration in clinical management of select cases where the concentration of these toxic antibiotics matters because of underlying co-morbidities. These results provide support to previous suggestions that re-consideration of breakpoint interpretations for polymyxins might be needed.
A double-blind, randomized, controlled trial of topical polysporin triple compound versus topical mupirocin for the eradication of colonization with methicillin-resistant Staphylococcus aureus in a complex continuing care population. [2021]Intranasal mupirocin or Polysporin Triple (PT) ointment (polymyxin B, bacitracin, gramicidin), in combination with chlorhexidine body washes, have been used for eradicating methicillin-resistant Staphylococcus aureus (MRSA), but no comparative studies have been done.
[Comparative evaluation of effectiveness of the effect of antibiotics and bacterial substances on clinical trains of Staphylococcus auerus isolated from patients with nonspecific ulcerative colitis]. [2006]The article presents of comparative analysis of sensitivity of Staphylococcus aureus clinical strains which were isolated from patients with non-specific ulcerative colitis to 9 widely used antibiotics. Biosporin action against these strains was also studied and a comparison of biosporin and antibiotics actions on the same strain was performed. The high degree of bacilli antagonism to polyresistant S. aureus strains has been revealed. The clear advantage of the therapeutic complex including biosporin as the most effective complex for growth inhibition and elimination of S. aureus from the contents of large intestine has been established.
The efficacy of Polysporin First Aid Antibiotic Spray (polymyxin B sulfate and bacitracin zinc) against clinical burn wound isolates. [2019]Polysporin First Aid Antibiotic Spray (Burroughs Wellcome Co., Research Triangle Park, N.C.) is a dry spray containing 200,000 units Aerosporin (polymyxin B sulfate) and 10,000 units bacitracin zinc, along with a propellant. Each 1-second spray delivers approximately 2300 units of polymyxin B sulfate and 115 units of bacitracin zinc. This study was designed to evaluate the efficacy of Polysporin Spray against various clinical isolates. Blood agar plates were inoculated with a pure culture of each isolate. Polysporin was then sprayed in an area approximately 30 mm in diameter. The area of inhibition was measured and recorded after 18 to 24 hours of incubation. A clear zone at least 20 mm in diameter with surrounding edges of growth indicated sensitivity. A zone less than 20 mm in diameter or growth over the whole plate indicated resistance. Three hundred fifty-three clinical isolates (202 gram positive and 151 gram negative) were tested. The results show that Polysporin inhibits the growth of all the gram-positive organisms, including methicillin-resistant strains of Staphylococcus. The gram-negative organisms were also sensitive to Polysporin Spray, with the exception of Serratia marcescens, Morganella morganii, and Proteus mirabilis. This study suggests that Polysporin First Aid Antibiotic Spray may be effective for wounds contaminated with gram-positive and some gram-negative organisms.
Synergistic activity of polymyxin B combined with vancomycin against carbapenem-resistant and polymyxin-resistant Acinetobacter baumannii: first in vitro study. [2019]The effect of a combination of polymyxin B (PMB) and vancomycin (VAN) was assessed against six Acinetobacter baumannii clinical isolates belonging to six different clusters (three PMB-susceptible and three PMB-resistant).
In vitro interactions of neomycin sulfate, bacitracin, and polymyxin B sulfate. [2019]Neomycin sulfate, bacitracin, and polymyxin B sulfate have been combined in topical preparations to provide a complementary antimicrobial spectrum for the prevention of minor wound infections. The advisability of the inclusion of neomycin sulfate has been questioned since it may cause contact sensitization.
Safety, Tolerability, Pharmacokinetics, and Drug Interaction Potential of SPR741, an Intravenous Potentiator, after Single and Multiple Ascending Doses and When Combined with β-Lactam Antibiotics in Healthy Subjects. [2020]SPR741 is a novel polymyxin B derivative, with minimal intrinsic antibacterial activity and reduced nonclinical nephrotoxicity compared to levels with polymyxin B, that interacts with the outer membrane of Gram-negative bacteria, enhancing penetration of coadministered antibiotics. The safety, tolerability, and pharmacokinetics (PK) of SPR741 were evaluated in two studies, after single and multiple intravenous (i.v.) doses in healthy adult subjects and after coadministration with partner antibiotics. In the single and multiple ascending-dose study, SPR741 or placebo was administered as a 1-h infusion at single doses of 5 to 800 mg and in multiple doses of 50 to 600 mg every 8 h (q8h) for 14 days. In the drug-drug interaction study, a single 400-mg i.v. dose of SPR741 was administered alone and in combination with piperacillin-tazobactam, ceftazidime, and aztreonam. PK parameters for SPR741 and partner antibiotics were determined using noncompartmental analysis. After single doses, a dose-linear and proportional increase in mean maximum concentration in plasma (Cmax) and area under the concentration-time curve (AUC) was observed. At doses of 100 to 800 mg, >50% of the dose was excreted in the urine in the first 4 h postdose. After multiple doses, the mean half-life was 2.2 h on day 1 and up to 14.0 h on day 14, with no evidence of accumulation after 14 days of dosing up to 400 mg. The PK profile of SPR741 and partner antibiotics was unchanged with coadministration. SPR741 was generally well tolerated at doses up to 1,800 mg/day. These data support further clinical development of SPR741 for treating serious infections due to resistant bacteria. (These studies have been registered at ClinicalTrials.gov under identifiers NCT03022175 and NCT03376529.).
Topical antibiotics and minor skin trauma. [2018]Recent double-blind controlled studies show that the application of a neomycin-bacitracin-polymyxin preparation reduces the incidence of staphylococcal and streptococcal infection of minor skin trauma. Allergic sensitization to neomycin is rare. Systemic side effects occur only with improper massive exposure. Resistant strains have appeared only in "closed populations." It is concluded that topical antibiotic combinations are safe and effective.
Global survey of polymyxin use: A call for international guidelines. [2021]Polymyxins (polymyxin B and colistin) are older bactericidal antibiotics that are increasingly used to treat infections caused by multidrug-resistant (MDR) Gram-negative bacteria. However, dosing and clinical use of these drugs vary widely. This survey was undertaken to reveal how polymyxins are used worldwide. Data were collected through a structured online questionnaire consisting of 24 questions regarding colistin usage patterns and indications as well as colistin dosage for adult patients. The questionnaire was disseminated in 2011 to relevant experts worldwide and was completed by 284 respondents from 56 different countries. Respondents from 11/56 countries (20%) had no access to colistin; 58/284 respondents (20.4%) reported that in 2010 they experienced that colistin was not available when needed. Formulations of polymyxins used were reported as: colistimethate sodium (48.6%); colistin sulfate (14.1%); both (1.4%); polymyxin B (1.4%); and unknown. Intravenous formulations were used by 84.2%, aerosolised or nebulised colistin by 44.4% and oral colistin for selective gut decontamination by 12.7%. Common indications for intravenous colistin were ventilator-associated pneumonia, sepsis and catheter-related infections with MDR Gram-negative bacteria. Only 21.2% of respondents used a colistin-loading dose, mainly in Europe and North America. This survey reveals that the majority of respondents use colistin and a few use polymyxin B. The survey results show that colistin is commonly underdosed. Clear guidance is needed on indications, dosing and antibiotic combinations to improve clinical outcomes and delay the emergence of resistance. Colistin should be considered a last-resort drug and its use should be controlled. International guidelines are urgently needed.
Comparison between Colistin and Polymyxin B in the Treatment of Bloodstream Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii-calcoaceticus Complex. [2023]Polymyxins are still widely used for the treatment of carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa bloodstream infections (BSIs). This study seeks to evaluate the impact of polymyxin B versus colistin on mortality and nephrotoxicity in BSI caused by these bacteria. We conducted a retrospective cohort study from 2014 to 2021 in Porto Alegre, Brazil. We included patients aged ≥18 years and excluded patients with polymicrobial infection or treatment for ≤48 h. The 30-day mortality was the primary outcome evaluated through Cox regression. We included 259 patients with BSI episodes: 78.8% caused by A. baumannii and 21.2% caused by P. aeruginosa. Polymyxin B did not impact mortality compared to colistin (adjusted hazard ratio (aHR), 0.82; 95% confidence interval (CI), 0.52-1.30; p = 0.40 (when adjusted for COVID-19 comorbidity, p = 0.05), Pitt bacteremia score, p < 0.01; Charlson comorbidity index, p < 0.001; time to start active antimicrobial therapy, p = 0.02). Results were maintained in the subgroups of BSI caused by A. baumannii (aHR, 0.92; 95% CI, 0.55-1.54; p = 0.74), P. aeruginosa (aHR, 0.47; 95% CI, 0.17-1.32; p = 0.15) and critical care patients (aHR, 0.77; 95% CI, 0.47-1.26; p = 0.30). Treatment with polymyxin B or colistin did not impact 30-day mortality in patients with carbapenem-resistant A. baumannii or P. aeruginosa BSI.
Prolonged direct hemoperfusion using a polymyxin B immobilized fiber cartridge provides sustained circulatory stabilization in patients with septic shock: a retrospective observational before-after study. [2020]Direct hemoperfusion therapy with polymyxin B immobilized fiber cartridges (PMX-DHP) is widely used for septic shock in Japan and parts of Europe. Although this treatment is usually administered for 2 h, the optimal duration has not been established.
Effects of polymyxin B hemoperfusion on hemodynamics and prognosis in septic shock patients. [2018]We designed this study to examine the clinical effects of polymyxin B hemoperfusion (PMX-HP) in septic shock patients.
Effects of Polymyxin B Hemoperfusion on Septic Shock Patients Requiring Noradrenaline: Analysis of a Nationwide Administrative Database in Japan. [2022]Polymyxin B hemoperfusion (PMX) reduces endotoxin in septic shock patients' blood and can improve hemodynamics and organ functions. However, its effects on the reduction of septic shock mortality are controversial.
The effect of direct hemoperfusion with polymyxin B immobilized cartridge on meropenem in critically ill patients requiring renal support. [2020]To evaluate the effect of direct hemoperfusion with polymyxin B immobilized cartridge (DHP-PMX) on meropenem pharmacokinetics in critically ill patients with sepsis requiring continuous venovenous hemofiltration (CVVH).
Endotoxin removal: how far from the evidence? From EUPHAS to EUPHRATES. [2019]There is a large amount of support for the safety of polymyxin-B (PMX-B) hemoperfusion in the treatment of septic shock from Japan and Europe. There is also support for potential efficacy, although randomized controlled trials are few and conflicting. PMX-B hemoperfusion represents a promising new treatment that could significantly improve survival. Previous clinical trials of PMX-B have been criticized for methodological issues, such as the absence of blinding, the use of surrogate outcomes and lack of longer term mortality outcomes. The variability in the number of treatment cartridges used, the selection of subjects based on likelihood of endotoxin presence without endotoxin measurement, and small sample sizes in mainly single-center trials have also been cited. The newly designed EUPHRATES trial (Evaluating Use of Polymyxin Hemoperfusion in a Randomized Controlled Trial of Adults treated for Endotoxemia and Septic Shock) addresses many of the methodological issues and represents a significant opportunity to test for clinical efficacy of endotoxin removal in the critically ill septic patient.