Blood Purification for Septic Shock

(PURIFY-RCT Trial)

Recruiting at 8 trial locations

Overseen By Lakhmir Chawla, M.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine

Must be taking: Antimicrobials

Disqualifiers: Pregnancy, Advanced cancer, Neutropenia, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 4 days

15 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be treated with specific antimicrobial agents listed in the Antimicrobial Management Guideline. If you need a different antimicrobial while in the trial, you will be removed from the study.

What data supports the idea that Blood Purification for Septic Shock (also known as: Seraph-100, Seraph 100 Microbind Blood Affinity Filter) is an effective treatment?

The available research shows that the Seraph-100 filter has been used effectively in patients with severe COVID-19, which can lead to septic shock. In one study, patients with severe COVID-19 and septic shock experienced improvements in their condition after treatment with the Seraph-100 filter. For example, a 17-year-old patient with severe COVID-19 and kidney issues improved significantly after using the filter, as he was able to stop using a ventilator and kidney therapy. Another study reported that two patients with severe COVID-19 pneumonia showed rapid improvement in their breathing and were discharged without needing extra oxygen after using the filter. While these studies focus on COVID-19, they suggest that the Seraph-100 filter can help improve conditions related to septic shock. ^{1 2 3 4 5}

What safety data is available for the Seraph-100 treatment?

The Seraph-100 Microbind Affinity Blood Filter has been used in various clinical settings, primarily under emergency use authorization for COVID-19 patients. Safety data from these studies indicate that the device has been used without significant adverse events. For example, in a case report involving an adolescent with severe COVID-19 and acute kidney injury, the patient tolerated the treatment well without significant adverse effects. Additionally, other studies have reported successful use in patients with severe COVID-19, showing improvements in clinical outcomes without notable safety concerns. ^{1 2 3 4 5}

Is the treatment Seraph-100 a promising treatment for septic shock?

Yes, the Seraph-100 treatment is promising for septic shock. It can remove harmful pathogens and substances from the blood, which may help improve the condition of patients with severe infections like COVID-19 and septic shock. Studies have shown that it can lead to rapid improvements in patients' health, such as better oxygen levels and recovery without needing extra oxygen. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial tests a special blood filter device in critically ill adults with severe infection and shock. The device works by filtering the blood outside the body to remove harmful substances, aiming to improve patient outcomes.

Research Team

Lakhmir Chawla, MD

Principal Investigator

ExThera Medical

Eligibility Criteria

Adults in the ICU with pathogen associated shock, needing drugs to maintain blood pressure after fluid resuscitation and having a detected bloodstream pathogen. Excludes those unlikely to survive 24 hours, at high bleeding risk, intolerant to extracorporeal therapy, with advanced cancer or neutropenia, pregnant/breastfeeding women, or allergic to heparin.

Inclusion Criteria

I was in the ICU needing drugs to keep my blood pressure up despite getting enough fluids.

A test found an infection in my blood within the last 3 days.

I was admitted to the ICU less than 3 days ago.

Exclusion Criteria

Your doctors do not expect you to live for more than one day.

High risk of bleeding (platelet count <50mm3 or International normalized ratio >1.5).

I cannot undergo treatments outside my body due to low blood pressure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive Seraph 100 treatment or 'State of the Art' care for up to 4 consecutive days

4 days

Daily visits (in-person) for treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at Day 7, Day 28, and 90 days post-enrollment

90 days

Multiple visits (in-person and virtual) at Day 7, Day 28, and 90 days

Pharmacokinetic Evaluation

First 15 patients undergo additional pharmacokinetic evaluation of antimicrobial removal by the filter treatment

Concurrent with treatment phase

Treatment Details

Interventions

• Seraph-100

Trial Overview The trial is testing Seraph-100 plus standard care against standard care alone for treating critically ill patients with shock due to pathogens. It's conducted across 15 U.S. sites and randomly assigns participants into two groups.

Participant Groups

Group I: 1- Seraph-100 plus State of the Art Care Experimental Treatment 1 Intervention

The Seraph 100 Filter is a single use, disposable column packed with ultra-high molecular weight polyethylene beads which have been modified to contain endpoint attached heparin on the surface. Seraph 100 is an extracorporeal broad-spectrum sorbent hemoperfusion device for reduction of pathogens from the bloodstream. It is intended for use with standard, commercially available bloodlines compatible with the pump system used. Female Luer connectors are required to connect to the Seraph 100 blood ports.

Group II: 2 - State of the Art Care Active Control 1 Intervention

"State of the Art care"is defined as the treatment algorithms outlined in the Surviving Sepsis Campaign for the treatment of septic shock, available at https://www.sccm.org/SurvivingSepsisCampaign/Home

Seraph-100 is already approved in United States for the following indications:

Approved in United States as Seraph 100 for:

• Pathogen-associated shock
• Sepsis

Who Is Running the Clinical Trial?

Henry M. Jackson Foundation for the Advancement of Military Medicine

Lead Sponsor

Trials

103

Recruited

94,300+

ExThera Medical Corporation

Lead Sponsor

Trials

8

Recruited

540+

Uniformed Services University of the Health Sciences

Collaborator

Trials

130

Recruited

91,100+

Findings from Research

The Seraph® 100 Microbind® Affinity Blood Filter was safely used in a 17-year-old kidney transplant patient with a severe adenovirus infection, showing no major adverse events during treatment.

Following two treatments with the Seraph® 100, the patient's viral load decreased significantly, leading to stabilization of her condition and allowing her to resume immunosuppression without a rebound in viral counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of the Seraph® 100 Microbind® Affinity Blood Filter in an adolescent patient with disseminated adenoviral disease. Li, DS., Burke, TM., Smith, JM., et al.[2023]

The Seraph® 100 Microbind® Affinity Blood Filter has a negligible effect on the clearance of antibiotics like vancomycin and gentamicin, suggesting that it does not significantly impact the ability to achieve pharmacodynamic targets for these drugs in patients with varying kidney function.

For antibiotics such as meropenem and imipenem, the use of Seraph 100 does not necessitate dose increases, as its intermittent use contributes minimally to antibiotic clearance, allowing for standard dosing protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemoperfusion with Seraph 100 Microbind Affinity Blood Filter Unlikely to Require Increased Antibiotic Dosing: A Simulations Study Using a Pharmacokinetic/Pharmacodynamic Approach. Selig, DJ., Reed, T., Chung, KK., et al.[2023]

In a study involving 9 patients with severe COVID-19 and septic shock, the Seraph-100® blood filter significantly improved critical health parameters, including mean arterial pressure and heart rate, indicating its potential efficacy in managing severe inflammatory responses.

The use of the Seraph-100® also led to a notable reduction in the need for vasopressors, suggesting it may help stabilize patients' hemodynamics during severe infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Center Experience With the Seraph-100® Microbind® Affinity Blood Filter in Patients With SARS-CoV-2 Infection and Septic Shock at a Military Treatment Facility. Stoffel, S., Boster, J., Jarrett, Z., et al.[2023]

The Seraph® 100 Microbind® Affinity Blood Filter was successfully used in a 17-year-old patient with severe COVID-19 complications, including acute kidney injury, demonstrating its potential for use in pediatric cases despite being previously authorized only for adults.

The patient tolerated the treatment well over a 5-day period with no significant adverse events reported, suggesting that the device may be safe for use in children under critical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Time Use of the Seraph&#174; 100 Microbind&#174; Affinity Blood Filter in an Adolescent Patient with Severe COVID-19 Disease: A Case Report. Merrill, KA., Krallman, KA., Loeb, D., et al.[2023]

The Seraph100 Microbind Affinity Blood Filter, used under Emergency Use Authorization, effectively removed viral particles and pro-inflammatory cytokines from the blood of two COVID-19 patients with rapidly increasing oxygen needs.

Both patients experienced a quick improvement in oxygen levels and were discharged from the hospital without needing supplemental oxygen, suggesting the filter's potential efficacy in treating severe COVID-19 cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two Patients With Severe COVID Pneumonia Treated With the Seraph-100 Microbind Affinity Blood Filter. Kelly, MM., Wilkinson, JD., Rastegar, M., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Use of the Seraph® 100 Microbind® Affinity Blood Filter in an adolescent patient with disseminated adenoviral disease. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Hemoperfusion with Seraph 100 Microbind Affinity Blood Filter Unlikely to Require Increased Antibiotic Dosing: A Simulations Study Using a Pharmacokinetic/Pharmacodynamic Approach. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Single-Center Experience With the Seraph-100® Microbind® Affinity Blood Filter in Patients With SARS-CoV-2 Infection and Septic Shock at a Military Treatment Facility. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

First-Time Use of the Seraph&#174; 100 Microbind&#174; Affinity Blood Filter in an Adolescent Patient with Severe COVID-19 Disease: A Case Report. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Two Patients With Severe COVID Pneumonia Treated With the Seraph-100 Microbind Affinity Blood Filter. [2022]