Therapeutic Plasma Exchange in Septic Shock: A Pilot Study (PLEXSIS)

August 12, 2025 updated by: University of Manitoba
The investigators propose to conduct a multi-center randomized pilot feasibility trial comparing therapeutic plasma exchange to standard of care in patients diagnosed with septic shock.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The intervention arm consists of an exchange of one volume of plasma equivalent to the patient's total calculated blood volume (1.0 plasma volume exchange) performed daily until discontinuation of vasopressors, death or up to a maximum of 5 daily treatments. Solvent detergent plasma or frozen plasma (FP) depending on availability will be used as the replacement fluid. The control group will receive standard of care for the treatment of septic shock in accordance with local practice and informed by national and international guidelines.

The management of septic shock, including but not limited to, antibiotic therapy, infection source control, therapy, fluid therapy, mechanical ventilation, and nutrition, will be at the discretion of the treating medical team, and will be recorded and reported.

The investigators will monitor for development of coagulopathy by measure the INR and fibrinogen levels daily. These are expected to normalize with the use of plasma as replacement fluid. The investigators will monitor for adverse reactions related to central venous access devices (insertion related complications, infection, thrombosis) and/or TPE (including reaction to plasma, allergic reactions and hypotension). Venous access devices will be inserted by trained, experienced personnel using real-time ultrasound guidance. These data are routinely collected by apheresis programs across Canada as part of a data collection and reporting relationship with CAG.

To further our understanding of the biologic impact of TPE in sepsis, plasma and whole blood samples will be collected at randomization (day 1), Pre-3rd TPE or Day 3 if in SOC group, pre-5th TPE or Day if SOC group, and 48 hours after completion of TPE or Day 7 if SOC group to evaluate markers of coagulation (ADAMTS-13 levels, DNase levels, histones).

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada
      • Calgary, Alberta, Canada
      • Edmonton, Alberta, Canada
        • Recruiting
        • University of Alberta
        • Principal Investigator:
          • Sean Bagshaw, MD
        • Contact:
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0W2
    • Ontario
      • Hamilton, Ontario, Canada
        • Recruiting
        • St. Joseph's Hospital
        • Principal Investigator:
          • Deborah Cook, MD
        • Contact:
          • France Clarke
      • Hamilton, Ontario, Canada
        • Recruiting
        • Hamilton Health Sciences - Juravinski
        • Principal Investigator:
          • Bram Rochwerg, MD
        • Contact:
          • Tina Millen
      • Kingston, Ontario, Canada, K7L2X3
        • Recruiting
        • Queen's University at Kingston
        • Principal Investigator:
          • Gordon Boyd
        • Contact:
      • Ottawa, Ontario, Canada
        • Recruiting
        • Ottawa Hospital
        • Principal Investigator:
          • Lauralyn McIntyre, MD
        • Contact:
      • Toronto, Ontario, Canada
    • Quebec
      • Montréal, Quebec, Canada, H2X 0C1
      • Quebec City, Quebec, Canada
        • Recruiting
        • Université Laval
        • Principal Investigator:
          • Alexis Turgeon, MD
        • Contact:
          • Stephanie Massana

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Eligible patients must be admitted to an ICU and must meet all of the following inclusion criteria:

  1. ≥ 16 years of age
  2. Refractory hypotension documented within 48 hours prior to enrollment requiring the institution and ongoing use of vasopressor agents (phenylephrine, norepinephrine, vasopressin, epinephrine, midodrine or dopamine >5 mcg/kg/min) at enrollment. Refractory hypotension is defined as a systolic blood pressure (SBP) less than 90 mmHg, or SBP less than 30 mmHg below baseline, or a mean arterial blood pressure less than 65 mmHg, despite adequate fluid resuscitation
  3. Capacity to initiate plasma exchange with 48 hours of vasopressor initiation.

  4. At least 1 other new organ dysfunction (in addition to refractory hypotension), defined by the following at the time of enrollment:

    1. Creatinine ≥1.5x the known baseline creatinine within 7 days, or ≥ 26.5 µmol/l increase in 48 hours,
    2. Need for invasive mechanical ventilation or a P/F ratio <250
    3. Platelets <100 x109/L, or a drop of 50 x109/L in the 3 days prior to enrollment
    4. Arterial pH < 7.30 or base deficit > 5 mmol/L in association with a lactate >/= to 3.0 mmol/L

45. Known or suspected infection

2.4.3 Exclusion criteria

We will exclude patients who have any one of the following criteria at the time of enrollment:

  1. Consent declined (refusal from patient, SDM, or physician)
  2. Clinically apparent alternate causes for shock (cardiogenic, hemorrhagic, obstructive, neurogenic or anaphylactic)
  3. Terminal illness with a life expectancy of less than 3 months
  4. Are pregnant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment Arm
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.
Other: Therapeutic Plasma Exchange
TPE procedures will be performed using a Spectra Optia ® apheresis machine (Terumo BCT, Lakewood, USA) according to usual-care procedures for apheresis. Venous access for the TPE procedures will be obtained through a double lumen dialysis catheter to provide adequate flow rates required for TPE. Regional citrate anticoagulation will be used for anticoagulation within the apheresis circuit. One to two grams of calcium chloride will be infused as per standard during TPE to prevent symptomatic hypocalcemia. Plasma volume will be calculated as per a standard formula whereby estimated plasma volume (in liters) = 0.07 x weight (kg) x (1 - hematocrit). In patients on dialysis, dialysis will be interrupted for the duration of the procedure. Antibiotics will be given after TPE to avoid clearance of the antibiotics. On the first day of TPE, a repeat dose of antibiotics will be administered after completion of TPE. Nurse clinicians trained in TPE will perform the TPE procedures.
No Intervention: Standard of Care Arm
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assess the feasibility of a large, multicenter trial of TPE in patients with septic shock
Time Frame: 18 months for enrollment
Assessing the feasibility of a large, multicenter trial of TPE in patients with septic shock will be the primary outcome. The primary measure of feasibility will be the ability to enroll an average of 2 patients per site per month.
18 months for enrollment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assess the rate of enrollment and adherence to the protocol of those enrolled
Time Frame: 18 months
The investigators will consider the consent rate to be adequate if 70% of SDM or patients when approached for consent are enrolled, an acceptable rate of protocol adherence to be 90% of all study participants; and the time from randomization to study treatment initiation to be satisfactory if this interval is less than 24 hours.
18 months
Number of participants that develop adverse reactions to TPE
Time Frame: Up to 8 days
The following will be recorded: a) major respiratory compromise; b) thrombotic events; c) major bleeding; d) anaphylaxis; e) central venous access insertion complications.
Up to 8 days
Further understand the biological impact of TPE in sepsis
Time Frame: up to 8 days
To further our understanding of the biologic impact of TPE in sepsis, sites will collect plasma and whole blood samples at randomization (day 1), pre-3rd TPE or day 3 if in SOC group, pre-5th TPE or day 5 if SOC group, and 48 hours after completion of last TPE or day 7 if SOC group to evaluate markers of coagulation (ADAMTS-13 levels, DNase levels, histones). Sites will collect whole blood samples on all randomized patients and profile DNA methylation on a random subset of 40 patients to determine changes in circulating immune cell remodeling.
up to 8 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: up to day 60
The pilot trial is not designed to detect differences in clinical outcomes. However, vital status will be accessed.
up to day 60
Organ failure
Time Frame: Up to day 21
The pilot trial is not designed to detect differences in clinical outcomes. However, the investigators will measure and describe organ-support free-days to day 21, and change in SOFA score (multiple organ dysfunction score).
Up to day 21
Organ failure
Time Frame: Up to day 8
The pilot trial is not designed to detect differences in clinical outcomes. However, the investigators will measure change in SOFA score (multiple organ dysfunction score).
Up to day 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Manitoba

Collaborators

Canadian Institutes of Health Research (CIHR)
Health Sciences Centre Foundation, Manitoba
McMaster University
University of Toronto

Investigators

  • Principal Investigator: Ryan Zarychanski, MD, MSc, University of Manitoba
  • Principal Investigator: Emily Rimmer, MD, MSc, University of Manitoba

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2023

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

July 19, 2021

First Submitted That Met QC Criteria

October 12, 2021

First Posted (Actual)

October 26, 2021

Study Record Updates

Last Update Posted (Actual)

August 17, 2025

Last Update Submitted That Met QC Criteria

August 12, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HS23165 (B2019:093)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The investigators do not plan to make individual participant data available to other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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