Therapeutic Plasma Exchange in Septic Shock: A Pilot Study

NCT05093075 | Recruiting Phase 2

• 1 other identifier: HS23165 (B2019:093)
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Septic Shock

Keywords

Sepsis

Outcome Measures

Primary Outcomes (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.

  18 months for enrollment

Secondary Outcomes (3)

• Assess the rate of enrollment and adherence to the protocol of those enrolled

  18 months

• Number of participants that develop adverse reactions to TPE

  Up to 8 days

• Further understand the biological impact of TPE in sepsis

  up to 8 days

Other Outcomes (3)

• Mortality

  up to day 60

• Organ failure

  Up to day 21

• Organ failure

  Up to day 8

Study Arms (2)

Treatment Arm

EXPERIMENTAL

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

Standard of Care Arm

NO 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.

Interventions

Therapeutic Plasma Exchange OTHER

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.

Treatment Arm

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 16 years of age
• 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
• Capacity to initiate plasma exchange with 48 hours of vasopressor initiation.
• At least 1 other new organ dysfunction (in addition to refractory hypotension), defined by the following at the time of enrollment:
• Creatinine ≥1.5x the known baseline creatinine within 7 days, or ≥ 26.5 µmol/l increase in 48 hours,
• Need for invasive mechanical ventilation or a P/F ratio \<250
• Platelets \<100 x109/L, or a drop of 50 x109/L in the 3 days prior to enrollment
• Arterial pH \< 7.30 or base deficit \> 5 mmol/L in association with a lactate \>/= to 3.0 mmol/L
• \. Known or suspected infection

You may not qualify if:

• We will exclude patients who have any one of the following criteria at the time of enrollment:
• Consent declined (refusal from patient, SDM, or physician)
• Clinically apparent alternate causes for shock (cardiogenic, hemorrhagic, obstructive, neurogenic or anaphylactic)
• Terminal illness with a life expectancy of less than 3 months
• Are pregnant

Sponsors & Collaborators

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

Study Sites (11)

Foothills Medical Centre

Calgary, Alberta, Canada

RECRUITING

Southern Health Campus

Calgary, Alberta, Canada

RECRUITING

University of Alberta

Edmonton, Alberta, Canada

RECRUITING

University of Manitoba

Winnipeg, Manitoba, R3E 0W2, Canada

RECRUITING

Hamilton Health Sciences - Juravinski

Hamilton, Ontario, Canada

RECRUITING

St. Joseph's Hospital

Hamilton, Ontario, Canada

RECRUITING

Queen's University at Kingston

Kingston, Ontario, K7L2X3, Canada

RECRUITING

Ottawa Hospital

Ottawa, Ontario, Canada

RECRUITING

St. Michael's Hospital

Toronto, Ontario, Canada

RECRUITING

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

Montreal, Quebec, H2X 0C1, Canada

RECRUITING

Universite Laval

Québec, Quebec, Canada

RECRUITING

Related Publications (7)

• 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.

  PMID: 27322218 BACKGROUND

• 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.

  PMID: 25527094 BACKGROUND

• 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.

  PMID: 12373468 BACKGROUND

• 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.

  PMID: 30515242 BACKGROUND

• 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.

  PMID: 18158437 BACKGROUND

• 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.

  PMID: 23659614 BACKGROUND

• 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.

  PMID: 31939781 BACKGROUND

MeSH Terms

Conditions

Shock, Septic; Sepsis

Interventions

Plasma Exchange

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Blood Transfusion; Biological Therapy; Therapeutics; Plasmapheresis; Blood Component Removal; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative

Study Officials

• Ryan Zarychanski, MD, MSc

  University of Manitoba

  PRINCIPAL INVESTIGATOR

• Emily Rimmer, MD, MSc

  University of Manitoba

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emily Rimmer, MD, MSc

CONTACT

204-787-2128; erimmer@cancercare.mb.ca

Chantale Pineau, BA

CONTACT

204-235-3223; chantale.pineau@umanitoba.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All investigators and research staff will be blinded to the allocation schedules. The PLEXSIS pilot trial is designed as a prospective randomized open, blinded endpoint (PROBE) trial. This pragmatic design is necessary given impractical nature of blinding the TPE intervention.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 19, 2021
• First Posted: October 26, 2021
• Study Start: June 1, 2023
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: August 17, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (11)