Plasma Exchange for Septic Shock

(PLEXSIS Trial)

Recruiting at 12 trial locations

Overseen By Chantale Pineau, BA

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Manitoba

Must be taking: Vasopressors

Disqualifiers: Pregnancy, Terminal illness, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 days

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether therapeutic plasma exchange, a procedure that replaces some blood plasma, can benefit people with septic shock, a severe infection causing dangerously low blood pressure. Researchers compare this treatment to the usual care for septic shock to determine its effectiveness. Suitable candidates for this trial include ICU patients with septic shock who have very low blood pressure despite treatment and another organ dysfunction, such as breathing difficulties or kidney problems. Participants will either receive plasma exchange treatment or continue with standard care practices. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What prior data suggests that Therapeutic Plasma Exchange is safe for patients with septic shock?

Research has shown that therapeutic plasma exchange (TPE) is generally safe for treating septic shock. Studies have found that TPE can stabilize blood pressure, reduce the need for heart-supporting medications, and improve organ function. For instance, one study found that fewer patients died shortly after treatment when they received TPE compared to those who did not.

Although some studies indicate that TPE may not always improve organ failure or reduce death rates in very sick patients, it is usually well-tolerated. Serious side effects are rare, making it a possible option for patients with septic shock.

Ongoing research aims to better understand how TPE can help. By participating in trials like this one, participants contribute to discovering if and how this treatment can be used more safely and effectively. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Therapeutic Plasma Exchange is unique because it offers a novel approach to treating septic shock by actively removing harmful substances from the blood, unlike the standard treatments which often focus on managing symptoms with fluids, antibiotics, and vasopressors. This method uses plasma exchange to filter out inflammatory mediators and toxins, potentially reducing the severity and duration of septic shock. Researchers are excited about this treatment because it could work faster than traditional methods, providing quicker stabilization for patients in critical condition.

What evidence suggests that therapeutic plasma exchange might be an effective treatment for septic shock?

Research has shown that therapeutic plasma exchange (TPE) might help with septic shock. In this trial, participants in the Treatment Arm will receive TPE. Some studies have found that TPE can lower the number of deaths shortly after treatment. For instance, one study showed a 20.5% decrease in deaths within 28 days when using TPE compared to regular treatment. However, not all studies agree, as some have not found clear benefits for organ function or long-term survival. Overall, early evidence suggests TPE could be helpful, but more research is needed to confirm this. Participants in the Standard of Care Arm will receive the usual treatment for septic shock according to local and international guidelines. ^{2 3 4 6 7}

Who Is on the Research Team?

Ryan Zarychanski, MD, MSc

Principal Investigator

University of Manitoba

Emily Rimmer, MD, MSc

Principal Investigator

University of Manitoba

Are You a Good Fit for This Trial?

This trial is for adults over 18 with septic shock, who have low blood pressure despite high-dose vasopressors and fluids, kidney injury as per KDIGO guidelines, need mechanical breathing support or have a low P/F ratio, significant drop in platelets, or severe acidosis with high lactate levels.

Inclusion Criteria

I am currently admitted to an intensive care unit.

I am 16 years old or older.

I have or might have an infection.

Exclusion Criteria

Are pregnant

Consent declined (refusal from patient, SDM, or physician)

My doctor expects I have less than 3 months to live.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily plasma exchanges until discontinuation of vasopressors, death, or up to a maximum of 5 daily treatments

Up to 5 days

Daily visits for plasma exchange

Follow-up

Participants are monitored for adverse reactions and biological impact of TPE, including coagulation markers and organ function

Up to 8 days

Regular monitoring visits

Long-term Follow-up

Participants' vital status and organ function are assessed to day 60

Up to 60 days

What Are the Treatments Tested in This Trial?

Interventions

• Therapeutic Plasma Exchange

Trial Overview The study tests if therapeutic plasma exchange can help patients with septic shock compared to standard treatments. Participants are randomly chosen to receive either the plasma exchange procedure or continue with their usual care without it.

How Is the Trial Designed?

Group I: Treatment Arm Experimental Treatment 1 Intervention

Participants randomized to the Treatment Arm will received 1.0 plasma exchanges daily until discontinuation of vasopressors, death or to a maximum of 5 daily treatments. Solvent detergent plasma (SDP) or frozen plasma (FP) depending on availability will be used as the replacement fluid.

Group II: Standard of Care Arm Active Control 1 Intervention

Participants randomized to the Control Arm will receive standard of care for the treatment of septic shock in accordance with local practice and informed by national and international guidelines.

Therapeutic Plasma Exchange is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Therapeutic Plasma Exchange for:

• Thrombotic thrombocytopenic purpura
• Guillain-Barré syndrome
• Multiple sclerosis
• Chronic inflammatory demyelinating polyradiculoneuropathy
• Lambert-Eaton syndrome
• Myasthenia gravis
• Goodpasture syndrome

Approved in United States as Therapeutic Plasma Exchange for:

• Thrombotic thrombocytopenic purpura
• Guillain-Barré syndrome
• Multiple sclerosis
• Chronic inflammatory demyelinating polyradiculoneuropathy
• Lambert-Eaton syndrome
• Myasthenia gravis
• Goodpasture syndrome
• Sepsis with multiorgan failure

Approved in Canada as Therapeutic Plasma Exchange for:

• Thrombotic thrombocytopenic purpura
• Guillain-Barré syndrome
• Multiple sclerosis
• Chronic inflammatory demyelinating polyradiculoneuropathy
• Lambert-Eaton syndrome
• Myasthenia gravis
• Goodpasture syndrome

Who Is Running the Clinical Trial?

University of Manitoba

Lead Sponsor

Trials

628

Recruited

209,000+

University of Toronto

Collaborator

Trials

739

Recruited

1,125,000+

Health Sciences Centre Foundation, Manitoba

Collaborator

Trials

17

Recruited

9,500+

McMaster University

Collaborator

Trials

936

Recruited

2,630,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

In a study of 230 patients undergoing therapeutic plasma exchange (PE) for neurological disorders, primarily Guillain-Barré Syndrome (GBS), the procedure was found to be safe with no reported mortality over a 48-month period.

The most common complications were minor, including paraesthesias and cramps (36.1%) and hypotension (32.2%), indicating that while some side effects occurred, they were not severe and did not lead to serious outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasmapheresis in neurological disorders: Experience from a tertiary care hospital in South India. Gafoor, VA., Jose, J., Saifudheen, K., et al.[2022]

In a study of 39 pediatric patients undergoing 172 therapeutic plasma exchange (TPE) sessions, TPE was found to be an effective treatment for various conditions, including macrophage activation syndrome and Guillain-Barre's syndrome, with no adverse events reported during the procedures.

The study suggests that TPE can be safely administered to children, with low rates of complications, indicating its potential for broader use in pediatric care for various diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Plasma Exchange Application in Children Requires Individual Decision. Atay, G., Demirkol, D.[2022]

Therapeutic Plasma Exchange (TPE) was performed on 161 patients over nine years, primarily for treating Guillain-Barre Syndrome (67.7%), and showed a 9.93% incidence of adverse reactions, indicating it is a generally safe procedure.

TPE demonstrated effectiveness as a treatment for neurological disorders, providing a viable alternative to Intravenous Immunoglobulin (IVIG), particularly in improving outcomes for conditions like Guillain-Barre Syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Plasma Exchange - An Emerging Treatment Modality in Patients with Neurologic and Non-Neurologic Diseases. Bobati, SS., Naik, KR.[2020]

In a study of 23 patients with severe sepsis or septic shock, therapeutic plasma exchange (TPE) was associated with significant reductions in fluid balance within 12 hours, indicating potential hemodynamic stabilization.

Out of the patients treated, 39% survived until ICU discharge, suggesting that early TPE therapy may benefit some patients, particularly those with high baseline SOFA scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic plasma exchange as rescue therapy in severe sepsis and septic shock: retrospective observational single-centre study of 23 patients. Hadem, J., Hafer, C., Schneider, AS., et al.[2021]

In a study of 42 patients undergoing 104 therapeutic plasma exchange (TPE) procedures, 75% showed improvement in their conditions, indicating that TPE is an effective treatment for diseases involving pathological proteins.

The most common conditions treated were polyradiculoneuropathies, myasthenia gravis, and Guillain-Barré syndrome, with the procedures primarily performed using a specific blood separator and citrate as an anticoagulant, highlighting the method's safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic plasma exchange in Casablanca. Tazi, I., Merimi, F., Majd, A., et al.[2008]

Therapeutic plasma exchange (TPE) is an effective blood purification method used in critical care, analyzed through 1188 procedures on 329 patients over a 10-year period, highlighting its role as a first-line or adjunct therapy.

The study aimed to evaluate TPE indications and outcomes, revealing important insights into patient responses and potential differences in adverse events between septic and non-septic cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic plasma exchange in an intensive care unit (ICU): a 10-year, single-center experience. Yilmaz, AA., Can, OS., Oral, M., et al.[2011]

Therapeutic plasma exchange (TPE) was safely administered to three neonates with septic shock, showing a significant reduction in lactate levels, which indicates improved metabolic status after treatment.

While TPE did not significantly change platelet levels, it appeared to improve organ failure indices in two of the three neonates, suggesting its potential as an adjunctive therapy in severe cases requiring extracorporeal life support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Plasma Exchange in Neonatal Septic Shock: A Retrospective Cohort Study. Sawyer, T., Billimoria, Z., Handley, S., et al.[2021]

In a study of 500 therapeutic plasma exchange (TPE) sessions conducted over 5 years on 68 patients, the procedure showed a low complication rate of 7.6%, with arterial hypotension being the most common issue.

The use of membrane filtration for TPE without anticoagulation was effective, as no significant symptoms related to electrolyte abnormalities were reported, although continuous monitoring of electrolytes is recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience in therapeutic plasma exchange by membrane filtration at an academic center in Colombia: Registry of the first 500 sessions. Córdoba, JP., Larrarte, C., Medina, MC.[2016]

In a study analyzing 883 plasma exchange procedures in 113 patients, 25.6% experienced adverse reactions, with most being mild or moderate, indicating that while complications can occur, they are generally not severe.

Patients with neurological diseases and those with hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP) were identified as high-risk groups for complications, but severe life-threatening events were rare, suggesting that plasma exchange is a safe treatment option overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of complications in therapeutic plasma exchange. Bramlage, CP., Schröder, K., Bramlage, P., et al.[2009]

Therapeutic plasma exchange (TPE) is effective for critically ill children, particularly for autoimmune neurological diseases, with a complete response rate of 64% and an overall survival rate of 92% at discharge from the pediatric intensive care unit (PICU).

Complications from TPE are generally mild, occurring in 17.4% of sessions, with transient hypotension being the most common issue, and there were no significant differences in outcomes between the two methods of TPE (centrifugation vs. membrane-based).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic plasma exchange in critically ill children: experience of the pediatric intensive care unit of two centers in Chile. Bustos B, R., Hickmann O, L., Cruces R, P., et al.[2022]

In a study of 16 septic shock patients, early initiation of therapeutic plasma exchange (TPE) within 4 hours of ICU admission significantly improved mean arterial pressure and reduced the need for norepinephrine, a critical vasopressor.

The results suggest that early TPE not only enhances hemodynamic stability but also leads to better fluid balance and reduced inflammation, as indicated by improved C-reactive protein levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of 4-hour rescue therapeutic plasma exchange in severe septic shock patients. Ahmed, RM., Soliman, AR., Yousry, A., et al.[2021]

Therapeutic Plasma Exchange (TPE) by filtration is considered a safe procedure with mild and manageable complications, such as thrombocytopenia (41%), hypocalcemia (18%), and hypotension (16%).

Despite its safety, the one-year mortality rate was 30%, primarily due to severe underlying conditions like pulmonary-renal syndrome and ANCA vasculitis, indicating that TPE is often used in critically ill patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic plasma exchange. Experience in 102 patients]. Ramírez-Guerrero, G., Müller-Ortiz, H., Jara-Vilugrón, F., et al.[2022]

Therapeutic plasma exchange (TPE) is increasingly recognized as a valuable treatment for antibody-mediated disorders in the perioperative setting, particularly for conditions like heparin-induced thrombocytopenia during urgent cardiac surgery.

TPE effectively removes harmful antibodies and immune complexes, improving outcomes in patients undergoing procedures such as solid-organ transplants and reducing the risk of postoperative complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Techniques and applications of perioperative therapeutic plasma exchange. Roman, PE., DeVore, AD., Welsby, IJ.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11193551/

Enhancing Survival in Septic Shock: A Systematic Review and ... The observational study between 2015 and 2019 found that plasma exchange therapy reduced mortality, improved SOFA scores, and improved fluid ...

2. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-023-04795-x

Influence of therapeutic plasma exchange treatment on short ... The adjunct TPE treatment (n = 300) showed a significant reduction in short-term mortality (RR 0.59, 95% CI 0.47–0.74, I2 3%) compared to ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10092885/

Therapeutic plasma exchange in patients with sepsis The results of this study suggest that TPE may not be associated with improvement of organ failure and mortality in critically ill patients with sepsis, and may ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05093075

NCT05093075 | Therapeutic Plasma Exchange in Septic ... A multi-center randomized pilot feasibility trial comparing therapeutic plasma exchange to standard of care in patients diagnosed with septic shock.

5. journals.sagepub.com journals.sagepub.com/doi/10.1177/00368504251352747

The application of therapeutic plasma exchange in sepsis ... The TPE group showed a 20.5% reduction in 28-day mortality compared to the SOC group, supporting its role as an adjunctive therapy for sepsis ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40696820/

The application of therapeutic plasma exchange in sepsis ... Emerging RCTs suggest that early initiation of TPE can stabilize hemodynamics, reduce vasopressor requirements, and improve organ function, ...

7. journals.lww.com journals.lww.com/shockjournal/fulltext/2024/05000/the_therapeutic_efficacy_of_plasmapheresis_for.6.aspx

the therapeutic efficacy of plasmapheresis for sepsis with ... Plasmapheresis was associated with reduced risk of 28-day mortality by 50% compared with conventional treatment (hazard ratio [HR], 0.50; 95% confidence ...