AzTrials
AzTrials

Septic ShockPhase 2PLEXSISNCT05093075

Therapeutic Plasma Exchange in Septic Shock: A Pilot Study

A Phase 2 study testing Therapeutic Plasma Exchange in people with Septic Shock, run by University of Manitoba at 11 sites in Canada.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
Septic Shock
What is being tested?
Therapeutic Plasma Exchange
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
11 sitesCanada
Study dates
1 Jun 2023to Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

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:
  5. Creatinine ≥1.5x the known baseline creatinine within 7 days, or ≥ 26.5 µmol/l increase in 48 hours,
  6. Need for invasive mechanical ventilation or a P/F ratio <250
  7. Platelets <100 x109/L, or a drop of 50 x109/L in the 3 days prior to enrollment
  8. Arterial pH < 7.30 or base deficit > 5 mmol/L in association with a lactate >/= to 3.0 mmol/L
  9. 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

Trial locations and contacts

11 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Emily Rimmer, MD, MSc contact

204-787-2128

erimmer@cancercare.mb.ca

Chantale Pineau, BA contact

204-235-3223

chantale.pineau@umanitoba.ca

11 sites in 1 country

Canada11 sites, 11 recruiting

  • Foothills Medical Centre

    Calgary, Alberta

    Theophany Eystathioy, theophany.eystathioy@ucalgary.ca

    Brent Winston, MD

    Recruiting

  • Southern Health Campus

    Calgary, Alberta

    Theophany Eystathioy, theophany.eystathioy@ucalgary.ca

    George Alvarez, MD

    Recruiting

  • University of Alberta

    Edmonton, Alberta

    Caylin Chadwick, caylin.chadwick@ahs.ca

    Sean Bagshaw, MD

    Recruiting

  • Hamilton Health Sciences - Juravinski

    Hamilton, Ontario

    Tina Millen

    Bram Rochwerg, MD

    Recruiting

  • St. Joseph's Hospital

    Hamilton, Ontario

    France Clarke

    Deborah Cook, MD

    Recruiting

  • Queen's University at Kingston

    Kingston, Ontario, K7L2X3

    Tracy Boyd, Tracy.Boyd@kingstonhsc.ca

    Gordon Boyd

    Recruiting

  • Centre Hospitalier de L'Université de Montréal (Chum),

    Montreal, Quebec, H2X 0C1

    Mélissa Gagnon-Hamelin, melissa.gagnon-hamelin.chum@ssss.gouv.qc.ca

    Han Ting Wang

    Recruiting

  • Ottawa Hospital

    Ottawa, Ontario

    Pieter Norgaard, pnorgaard@ohri.ca

    Lauralyn McIntyre, MD

    Recruiting

  • Universite Laval

    Québec, Quebec

    Stephanie Massana

    Alexis Turgeon, MD

    Recruiting

  • St. Michael's Hospital

    Toronto, Ontario

    Marlene Santos, Marlene.Santos@unityhealth.to

    Katerina Pavenski, MD

    Recruiting

  • University of Manitoba

    Winnipeg, Manitoba, R3E 0W2

    Chantale Pineau, MA, 2042353223, chantale.pineau@umanitoba.ca

    Recruiting

Other trials in Canada

About this study

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.

Read the 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).

Conditions
Septic Shock
Being tested
Therapeutic Plasma Exchange
Keywords
Sepsis
Medical subject headings
Shock, Septic, Sepsis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Therapeutic Plasma ExchangeOther

    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.

Study groups in NCT05093075
Study groupRoleWhat they receive
Treatment ArmExperimentalParticipants 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.
Receives: Other: Therapeutic Plasma Exchange
Standard of Care ArmNo interventionParticipants 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 being measured

The primary outcome is the main question the study is designed to answer.

  1. Assess the feasibility of a large, multicenter trial of TPE in patients with septic shock

    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.

    Measured: 18 months for enrollment

Secondary outcomes (3)

  1. Assess the rate of enrollment and adherence to the protocol of those enrolled

    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.

    Measured: 18 months

  2. Number of participants that develop adverse reactions to TPE

    The following will be recorded: a) major respiratory compromise; b) thrombotic events; c) major bleeding; d) anaphylaxis; e) central venous access insertion complications.

    Measured: Up to 8 days

  3. Further understand the biological impact of TPE in sepsis

    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.

    Measured: up to 8 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Oct 2021
  2. Study start1 Jun 2023
  3. Primary completionMar 2027 (estimated)
  4. Study completionDec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
A web-based randomization system maintained at the Center for Healthcare Innovation (CHI) (Winnipeg, Manitoba) will be used to allocate treatment assignments. The randomization process will consist of a computer-generated random listing of the treatment allocations in variable permuted blocks of 2 and 4. Participants will be randomized to Treatment (5 Therapeutic Plasma Exchanges) or Standard of Care.
Masking
Double blind
Who is masked
Investigator, Outcomes assessor
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05093075
Sponsor's protocol ID
HS23165 (B2019:093)
Acronym
PLEXSIS
Status last verified
Aug 2025
First submitted
19 Jul 2021
Last updated
17 Aug 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: The investigators do not plan to make individual participant data available to other researchers.

Publications

  • Schwartz J, Padmanabhan A, Aqui N, Balogun RA, Connelly-Smith L, Delaney M, Dunbar NM, Witt V, Wu Y, Shaz BH. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Seventh Special Issue. J Clin Apher. 2016 Jun;31(3):149-62. doi: 10.1002/jca.21470.

    PubMed 27322218

  • Rimmer E, Houston BL, Kumar A, Abou-Setta AM, Friesen C, Marshall JC, Rock G, Turgeon AF, Cook DJ, Houston DS, Zarychanski R. The efficacy and safety of plasma exchange in patients with sepsis and septic shock: a systematic review and meta-analysis. Crit Care. 2014 Dec 20;18(6):699. doi: 10.1186/s13054-014-0699-2.

    PubMed 25527094

  • Busund R, Koukline V, Utrobin U, Nedashkovsky E. Plasmapheresis in severe sepsis and septic shock: a prospective, randomised, controlled trial. Intensive Care Med. 2002 Oct;28(10):1434-9. doi: 10.1007/s00134-002-1410-7. Epub 2002 Jul 23.

    PubMed 12373468

  • Davies R, O'Dea K, Gordon A. Immune therapy in sepsis: Are we ready to try again? J Intensive Care Soc. 2018 Nov;19(4):326-344. doi: 10.1177/1751143718765407. Epub 2018 Apr 4.

    PubMed 30515242

  • Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL; International Surviving Sepsis Campaign Guidelines Committee; American Association of Critical-Care Nurses; American College of Chest Physicians; American College of Emergency Physicians; Canadian Critical Care Society; European Society of Clinical Microbiology and Infectious Diseases; European Society of Intensive Care Medicine; European Respiratory Society; International Sepsis Forum; Japanese Association for Acute Medicine; Japanese Society of Intensive Care Medicine; Society of Critical Care Medicine; Society of Hospital Medicine; Surgical Infection Society; World Federation of Societies of Intensive and Critical Care Medicine. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008 Jan;36(1):296-327. doi: 10.1097/01.CCM.0000298158.12101.41.

    PubMed 18158437

  • Lega JC, Mismetti P, Cucherat M, Fassier T, Bertoletti L, Chapelle C, Laporte S. Impact of double-blind vs. open study design on the observed treatment effects of new oral anticoagulants in atrial fibrillation: a meta-analysis. J Thromb Haemost. 2013 Jul;11(7):1240-50. doi: 10.1111/jth.12294.

    PubMed 23659614

  • Binnie A, Walsh CJ, Hu P, Dwivedi DJ, Fox-Robichaud A, Liaw PC, Tsang JLY, Batt J, Carrasqueiro G, Gupta S, Marshall JC, Castelo-Branco P, Dos Santos CC; Epigenetic Profiling in Severe Sepsis (EPSIS) Study of the Canadian Critical Care Translational Biology Group (CCCTBG). Epigenetic Profiling in Severe Sepsis: A Pilot Study of DNA Methylation Profiles in Critical Illness. Crit Care Med. 2020 Feb;48(2):142-150. doi: 10.1097/CCM.0000000000004097.

    PubMed 31939781

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Therapeutic Plasma Exchange in people with Septic Shock, run by University of Manitoba at 11 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 17 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Emily Rimmer, MD, MSc (204-787-2128, erimmer@cancercare.mb.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Assess the feasibility of a large, multicenter trial of TPE in patients with septic shock (time frame: 18 months for enrollment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05093075, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in