PMX Hemoperfusion for Septic Shock

(TIGRIS Trial)

Not currently recruiting at 21 trial locations

Overseen By Esha Kamaluddin

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Spectral Diagnostics (US) Inc.

Must be taking: Vasopressors, Antibiotics

Disqualifiers: End-stage renal disease, Severe heart failure, Recent AMI, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 30

Duration: 3 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method for treating septic shock, a severe reaction to infection, using a device called the PMX cartridge, which utilizes Polymyxin B, an antibiotic. Researchers aim to determine if adding this device to standard medical care improves recovery compared to standard care alone. The trial is open to individuals with septic shock who require medication to support blood pressure, have undergone recent fluid resuscitation, and are currently battling an infection. Participants will receive either standard care plus the PMX cartridge treatment or standard care alone. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could enhance future septic shock treatments.

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 prior data suggests that the PMX cartridge is safe for treating septic shock?

Research has shown that PMX hemoperfusion, a treatment using a special filter to clean the blood, is generally safe for people with septic shock. Studies have found that this treatment can reduce the risk of death within 28 days for those with sepsis or septic shock.

The PMX filter, also known as Toraymyxin, has been tested for safety and is well-tolerated. No significant increase in unwanted side effects occurs in people who receive the treatment compared to those who do not. This indicates that patients usually do not experience more serious problems due to the treatment.

Overall, PMX hemoperfusion appears to be a promising option that is both effective and safe for people dealing with septic shock. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about PMX hemoperfusion for septic shock because it offers a novel approach to treatment by using the PMX cartridge, which contains Polymyxin B. Unlike traditional treatments that rely on antibiotics and supportive care, this technique directly targets and removes endotoxins from the bloodstream, which are a major contributor to septic shock. This method could potentially lead to faster stabilization of patients and reduce the severity of their condition. By efficiently clearing these harmful substances, PMX hemoperfusion has the potential to be a game-changer in managing septic shock, offering hope for improved outcomes.

What evidence suggests that the PMX cartridge is effective for septic shock?

Research has shown that the PMX cartridge, which uses polymyxin B, may help treat septic shock. In this trial, participants in the PMX Treatment arm will receive standard medical care for septic shock plus treatment with the PMX cartridge. Studies have found that this treatment can reduce deaths within 28 days for people with septic shock. Additionally, patients who received PMX treatment often had better blood pressure control within 48 hours of starting it. Real-world results also suggest that PMX therapy can improve survival chances for those with severe sepsis or septic shock. Overall, evidence supports PMX hemoperfusion as an effective option for managing septic shock. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

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.

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

I weigh less than 35 kg (77 pounds).

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Polymyxin B

Trial Overview

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.

How Is the Trial Designed?

Group I: PMX Treatment Experimental Treatment 1 Intervention

Standard medical care for septic shock plus treatment with the PMX cartridge (twice approximately 24 hours apart)

Group II: Control Active Control 1 Intervention

Standard medical care alone

Who Is Running the Clinical Trial?

Spectral Diagnostics (US) Inc.

Lead Sponsor

Trials

4

Recruited

600+

Published Research Related to This Trial

Polymyxin-B hemoperfusion has shown promising safety and potential efficacy in treating septic shock, particularly supported by studies from Japan and Europe, despite a lack of robust randomized controlled trials.

The EUPHRATES trial aims to address previous methodological flaws in studies of PMX-B, providing a significant opportunity to evaluate its effectiveness in removing endotoxins in critically ill patients with septic shock.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endotoxin removal: how far from the evidence? From EUPHAS to EUPHRATES. Rachoin, JS., Foster, D., Dellinger, RP.[2019]

In a clinical trial involving 103 asymptomatic MRSA carriers, mupirocin was significantly more effective than Polysporin Triple (PT) ointment in eradicating MRSA, with 65% of mupirocin patients testing MRSA negative at 48 hours compared to only 31% in the PT group.

At the 12-week follow-up, mupirocin showed a 30.8% eradication rate at all sites, while only 2.8% of PT-treated patients achieved the same, indicating that mupirocin is a superior option for MRSA eradication when used with chlorhexidine body washes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. O'Grady, S., Hirji, Z., Pejcic-Karapetrovic, B., et al.[2021]

Prolonged direct hemoperfusion therapy with polymyxin B (PMX-DHP) for 12 hours resulted in significantly better blood pressure stabilization and reduced vasopressor dependency compared to the conventional 2-hour treatment in a study of 36 patients with septic shock.

Despite the improved circulatory stabilization with prolonged PMX-DHP, there was no difference in hospital mortality rates between the two treatment durations, indicating that while the therapy may enhance hemodynamic support, it does not necessarily lead to better survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Miyamoto, K., Kawazoe, Y., Kato, S.[2020]

In a study of 30,731 septic shock patients, those treated with polymyxin B hemoperfusion (PMX) had a significantly higher 28-day survival rate of 77.9% compared to 71.1% in the control group, suggesting PMX may improve outcomes in septic shock.

Patients receiving PMX also experienced more days free from noradrenaline, ventilators, and continuous hemodiafiltration, indicating improved organ function and hemodynamics, particularly in those requiring lower doses of noradrenaline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Polymyxin B Hemoperfusion on Septic Shock Patients Requiring Noradrenaline: Analysis of a Nationwide Administrative Database in Japan. Fujimori, K., Tarasawa, K., Fushimi, K.[2022]

In a study of 69 septic shock patients, those treated with polymyxin B hemoperfusion (PMX-HP) showed a significant reduction in inotropic scores after 24 hours compared to those receiving conventional treatment, indicating improved hemodynamic stability.

PMX-HP was associated with a lower 28-day mortality rate (odds ratio 0.18), suggesting it may enhance survival outcomes for patients with septic shock due to intra-abdominal or gram-negative infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of polymyxin B hemoperfusion on hemodynamics and prognosis in septic shock patients. Lee, CT., Tu, YK., Yeh, YC., et al.[2018]

Polysporin First Aid Antibiotic Spray effectively inhibits the growth of all tested gram-positive bacteria, including methicillin-resistant Staphylococcus strains, indicating its potential for treating infections caused by these organisms.

The spray also shows effectiveness against many gram-negative bacteria, although it is not effective against Serratia marcescens, Morganella morganii, and Proteus mirabilis, suggesting it may be suitable for a wide range of wound infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of Polysporin First Aid Antibiotic Spray (polymyxin B sulfate and bacitracin zinc) against clinical burn wound isolates. Walton, MA., Carino, E., Herndon, DN., et al.[2019]

A comparative analysis of Staphylococcus aureus strains from patients with non-specific ulcerative colitis showed that biosporin was highly effective in inhibiting the growth of polyresistant S. aureus strains.

The study found that a therapeutic complex including biosporin was superior to conventional antibiotics in eliminating S. aureus from the large intestine, highlighting its potential as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[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]. Tropko, LV.[2006]

The combination of polymyxin B (PMB) and vancomycin (VAN) showed a synergistic effect against six clinical isolates of Acinetobacter baumannii, including both PMB-susceptible and PMB-resistant strains, indicating its potential as an effective treatment option.

The PMB-VAN combination demonstrated a bactericidal effect within 24 hours against PMB-resistant isolates, suggesting it may help prevent hypermutation in these bacteria, which is crucial for overcoming antibiotic resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic activity of polymyxin B combined with vancomycin against carbapenem-resistant and polymyxin-resistant Acinetobacter baumannii: first in vitro study. Shinohara, DR., Menegucci, TC., Fedrigo, NH., et al.[2019]

In a study involving critically ill patients with sepsis undergoing continuous venovenous hemofiltration, direct hemoperfusion with polymyxin B immobilized cartridge (DHP-PMX) did not significantly alter the pharmacokinetics of meropenem, a crucial antibiotic.

Key pharmacokinetic parameters such as the area under the curve (AUC), peak and trough concentrations, and half-life of meropenem remained comparable with and without DHP-PMX therapy, indicating that DHP-PMX does not clinically impact meropenem effectiveness in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of direct hemoperfusion with polymyxin B immobilized cartridge on meropenem in critically ill patients requiring renal support. Singhan, W., Vadcharavivad, S., Areepium, N., et al.[2020]

Neomycin sulfate, when combined with bacitracin and polymyxin B, shows strong synergistic effects against common wound infection bacteria, suggesting its continued use in topical preparations despite safety concerns.

The study indicates that the three-drug combination can potentially allow for lower concentrations of antibiotics in formulations while maintaining efficacy, which could enhance safety and reduce the risk of sensitization associated with neomycin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro interactions of neomycin sulfate, bacitracin, and polymyxin B sulfate. Booth, JH., Benrimoj, SI., Nimmo, GR.[2019]

A global survey of 284 healthcare experts revealed that colistin, an antibiotic used for multidrug-resistant Gram-negative infections, is often underdosed, with only 21.2% of respondents using a loading dose, which is crucial for effective treatment.

The survey highlighted the need for clear international guidelines on the indications and dosing of colistin to improve patient outcomes and prevent antibiotic resistance, as 20% of respondents reported colistin was unavailable when needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Global survey of polymyxin use: A call for international guidelines. Wertheim, H., Van Nguyen, K., Hara, GL., et al.[2021]

In a study of 259 patients with bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, treatment with polymyxin B did not significantly affect 30-day mortality compared to colistin.

Both polymyxin B and colistin showed similar outcomes in terms of mortality rates, indicating that neither drug provided a clear advantage in treating these infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison between Colistin and Polymyxin B in the Treatment of Bloodstream Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii-calcoaceticus Complex. Garcia, RCL., Rodrigues, RD., Garcia, ECL., et al.[2023]

Polymyxin B demonstrated significantly lower minimum inhibitory concentrations (MICs) compared to colistin against multidrug-resistant bacteria, including Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, suggesting it may be more effective in treating infections caused by these organisms.

The study indicates that while the differences in categorical interpretations of susceptibility were minimal, the lower MICs of polymyxin B could be crucial in clinical settings, especially for patients with co-morbidities where antibiotic toxicity is a concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of antibacterial activities of polymyxin B and colistin against multidrug resistant Gram negative bacteria. Doymaz, MZ., Karaaslan, E.[2020]

SPR741, a new derivative of polymyxin B, shows reduced nephrotoxicity and enhances the effectiveness of coadministered antibiotics against Gram-negative bacteria, making it a promising option for treating serious infections.

In clinical studies involving healthy adults, SPR741 was well tolerated at doses up to 1,800 mg/day, with a favorable pharmacokinetic profile that supports its further development for combating antibiotic-resistant infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Eckburg, PB., Lister, T., Walpole, S., et al.[2020]

Topical application of a neomycin-bacitracin-polymyxin antibiotic preparation significantly reduces the risk of staphylococcal and streptococcal infections in minor skin injuries, based on recent double-blind controlled studies.

The combination is considered safe, with rare allergic reactions to neomycin and systemic side effects only occurring with excessive use, indicating its efficacy in preventing infections without major safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical antibiotics and minor skin trauma. Leyden, JJ., Sulzberger, MB.[2018]

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In patients with septic shock, early administration of PMX-HP was associated with higher mean arterial pressure and lower VIS within 48 h after ICU admission.

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