Septic ShockPhase 1NCT04057872
Therapeutic Plasma Exchange in Adult Patients With Severe Sepsis
A Phase 1 study testing Therapeutic plasma exchange in people with Septic Shock, run by Alberta Health Services, Calgary at 2 sites in Canada.
Trial summary
The incidence of sepsis (severe infection) has increased over the last four decades. Severe sepsis and septic shock are among the leading causes of death for patients admitted to critical care units with mortality ranging from 20-70% depending on totality of organ dysfunction. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock
- What is being tested?
- Therapeutic plasma exchange
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 2 sitesCanada
- Study dates
- 21 Oct 2020to 31 Dec 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Inclusion Criteria Adult patients (age ≥18) with a documented or strong clinical suspicion of infection that meets the definition of septic shock as per the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).
Exhibiting two of the four clinical signs of inflammation:
- Core temperature > 38oC or < 36oC
- Heart rate > 90 beats per minute
- Respiratory rate > 20 breaths per minute, or PaCO2 < 32 mmHg, or mechanical ventilation
- White cell count > 12 x 109/L or < 4 x 109/L or > 10% immature neutrophils
We will further identify the subset with a hospital mortality in excess of 40%:
- >30 mls/kg fluid resuscitation
- Noradrenaline >0.1 ug/kg/min to maintain MAP> 65mmHg for at least 4 consecutive hours and present at initiation of TPE
- Lactate >2 mmol/l.
Exclusion Criteria Patients will be excluded in cases where death is deemed inevitable or imminent during admission and either the attending physician, patient or surrogate legal decision maker is not committed to active treatment.
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Peter Lougheed Centre
Calgary, Alberta, T3M 1M4
South Health Campus
Calgary, Alberta, T3M 1M4
About this study
Official title: PILOT STUDY in the Use of Therapeutic Plasma Exchange in Adult Patients With Severe Sepsis
The incidence of sepsis (severe infection) has increased over the last four decades. Severe sepsis and septic shock are among the leading causes of death for patients admitted to critical care units with mortality ranging from 20-70% depending on totality of organ dysfunction. Outside of antibiotics and good bedside care, little has changed in the management of this life-threatening problem.
Therapeutic plasma exchange (TPE) involves the separation of plasma from whole blood. The removed plasma is 'exchanged or replaced' with either IV fluids, albumin, blood products or a combination thereof.
The primary objective of this study is to evaluate the safety of the TPE intervention protocol within 24 hours of study criteria being met. TPE is now a well-established program at the South Health Campus for neuro-muscular disorders. Since starting in May 2018, the investigators have performed over 150 runs making the SHC ICU one of the most experienced centers in Canada.
Read the detailed description
Background
The incidence of sepsis has increased over the last four decades (1). Sepsis is a life-threatening condition that arises when the body's response to an infection injures its own tissues and organs. Severe sepsis and septic shock are among the leading causes of death for patients admitted to critical care units with mortality ranging from 20-70% depending on totality of organ dysfunction (2, 3). The literature is replete with initial promising phase 2 therapies failing in definitive randomized trails (4-8). In fact, a recent systematic review concluded that no evidence exists for any pharmacologic intervention that has consistently reduced mortality in critically ill patients (9). This is both surprising and frustrating for the author. The most recent guidelines have tried to redefine sepsis as a 'syndrome' since neither validated criterion nor do standard diagnostic tests exist (10). The authors argue that sepsis should be viewed as organ dysfunction caused by a dysregulated or non-homeostatic host response. Most of the clinical manifestations of severe infections are caused by an intense, generalized inflammatory response in the host mediated by a multitude of interrelated cellular and humoral factors (3).
Plasmapheresis or therapeutic plasma exchange (TPE) involves the separation of plasma from whole blood. The removed plasma is 'exchanged or replaced' with crystalloids, albumin, fresh frozen plasma or a combination thereof. TPE use is well established in many neurological disorders including Guillain-Barre syndrome (11), Myasthenia Gravis (12, 13) and antibody mediated syndromes(14, 15). It is considered the standard of care for thrombotic thrombocytopenic purpura (TTP) (16, 17). The rationale for the use of TPE in sepsis, a non-selective intervention, is to remove multiple toxic mediators including endotoxins, activated complement, pro-inflammatory cytokines and pro-coagulant factors (18, 19). If fresh-frozen plasma is used as replacement fluid, consumed plasma factors are substituted, thereby possibly restoring the opsonic capacity and improving the coagulation abnormalities and microcirculation.
Plasma exchange has been reported since the late 1970s as a potential adjunctive or salvage therapy in severe sepsis in both pediatric and adult patients (20-24). These case reports, retrospective reviews and observational studies suggest a survival advantage when compared to historical controls. However, the obvious bias limits any meaningful interpretation. A literature review found only 4 studies with any attempt at randomization. One study enrolled only adults (25), two were exclusively pediatric patients (26, 27) and one study involved both adults and children (28). Excluding the pediatric studies, the adult protocols had few similarities:
- Reeves and colleagues attempted a multi-center Australian study but terminated enrollment after 22 adult and 8 children (28). The mean APACHEII scores for adults were 25.2. They aggressively exchanged 5 plasma volumes continuously over 36 hours using a combination of fresh frozen plasma (FFP) and albumin (1/4 ratio). Mortality was reported at 14 days. No data on ICU or hospital length of stay was provided. This trial reported significant decrease in certain inflammatory markers.
- Busund's larger trail involved 106 adults and reported mortality at 28 days (25). They performed a single 30-40mls/kg exchange that could be repeated once if no clinical improvement was observed. The replacement used was FFP and albumin in a 1:1 ratio. Six episodes of transient hypotension and 1 allergic reaction to FFP was reported (the only trial to report adverse events). There was an encouraging trend towards improved survival (33% vs 53%) versus historical controls. No data on ICU or hospital length of stay was provided.
A more recent German pilot study tried to evaluate the safety and feasibility of enrollment within 12 hours of shock for a proposed randomized controlled trial (RCT) (29). The inclusion criteria were simple: (a) Current sepsis-3 definitions; noradrenaline dose >0.4ug/kg/min despite >30mls/kg of crystalloid; (b) Less than 12 hours of vasopressor support. They performed a single 1.2x plasma exchange using entirely FFP. The major findings were significantly less vasopressor support, fluid balance and a decline in plasma concentrations of pro-inflammatory mediators. The "sustained -responders" mortality was 43% vs 77% of non-responders, but the small numbers prevented statistical significance.
The use of plasma exchange in severe sepsis is graded by the American Society for Apheresis as category III with grade 2C indications, indicating that there is a lack of reliable trials to support TPE use in the condition (30). The purpose of this phase 1 clinical trial is to assess the safety of using plasma exchange in critically ill adult patients with septic shock. TPE is now a well-established program at the South Health Campus (SHC) for neuro-muscular disorders. Since starting in May 2018, we have performed over 240 runs in 43 patients making the SHC ICU the most experienced TPE center in Canada in the past 2 years. One plasma volume is currently the standard dose used safely in patients with neuro-muscular disorders at SHC.
Justification of Research
- The incidence of sepsis has increased over 4 decades but no single pharmacological invention reduces mortality/morbidity.
- A potential treatment that increases the chance of survival and recovery in patients with septic shock would be both beneficial to patients and help decrease medical costs from long term stays in the ICU.
- The maximum tolerable dose of TPE in septic patients is unknown.
Study Objectives
Primary Objective: To evaluate the safety of the TPE intervention protocol within 24 hours of study criteria being met.
Secondary Objectives:
- To evaluate preliminary efficacy of the TPE protocol.
- To determine maximum tolerable dose of TPE in septic patients.
- To record adverse events from TPE intervention.
Hypothesis
It is hypothesized that TPE will be safe for use in patients with septic shock. We will determine the maximum tolerable dose via a dose escalation study.
- Conditions
- Septic Shock
- Being tested
- Therapeutic plasma exchange
- Keywords
- Therapeutic Plasma Exchange (TPE), Septic Shock, Severe Sepsis, Albumin, Fresh Frozen Plasma
- 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 exchangeProcedure or surgery
The removed plasma is 'exchanged or replaced' with either IV fluids, albumin, and/or Fresh frozen plasma
| Study group | Role | What they receive |
|---|---|---|
| TPE in Septic Shock | Experimental | The patients will undergo a dosing trial to determine safety and the most effective dose Receives: Procedure: Therapeutic plasma exchange |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
Proportion of patients who experience at least 1 Adverse Event (AE)
Measured: During course of ICU stay, could be up to 6 months
Discontinue TPE
Proportion of patients who discontinue TPE administration due to an AE
Measured: During course of ICU stay, could be up to 6 months
Enrollment Rate
- Enrollment rate (patients screened, patients eligible, patients approached, patients enrolled)
Measured: During course of ICU stay, could be up to 6 months
Protocol Completion
Protocol completion (patients who complete study protocol)
Measured: During course of ICU stay, could be up to 6 months
Secondary outcomes (6)
Organ dysfunction
Resolution or worsening of organ dysfunction as per SOFA score
Measured: During course of ICU stay, could be up to 6 months
Vasopressor support
Hours of vasopressor support
Measured: During course of ICU stay, could be up to 6 months
Ventilator support
Days on ventilator if applicable
Measured: During course of ICU stay, could be up to 6 months
Days in ICU
Days in ICU (censored to day ready for discharge)
Measured: During course of ICU stay, could be up to 6 months
Mortality
Mortality
Measured: During course of ICU stay, could be up to 6 months
RRT Required
Need for RRT
Measured: During course of ICU stay, could be up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2019
- Study start21 Oct 2020
- Primary completion31 Dec 2024
- Study completion31 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (30)Papers the sponsor has linked to this study.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Consecutive Adults patients with vasoplegic septic shock with at least 2 organ dysfunction will receive TPE
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alberta Health Services, Calgary
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. George Alvarez, Alberta Health Services, Calgary
- Investigators
- George F Alvarez, MD, Principal investigator, Alberta Health services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04057872
- Sponsor's protocol ID
- REB19-1157
- Status last verified
- Apr 2025
- First submitted
- 2 Aug 2019
- Last updated
- 3 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Once the results have been analyzed and published the de-identified data will be made available to other researchers
Publications
Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003 Apr 17;348(16):1546-54. doi: 10.1056/NEJMoa022139.
PubMed 12700374Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013 Aug 29;369(9):840-51. doi: 10.1056/NEJMra1208623. No abstract available.
PubMed 23984731Minasyan H. Sepsis and septic shock: Pathogenesis and treatment perspectives. J Crit Care. 2017 Aug;40:229-242. doi: 10.1016/j.jcrc.2017.04.015. Epub 2017 Apr 18.
PubMed 28448952Fisher CJ Jr, Dhainaut JF, Opal SM, Pribble JP, Balk RA, Slotman GJ, Iberti TJ, Rackow EC, Shapiro MJ, Greenman RL, et al. Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group. JAMA. 1994 Jun 15;271(23):1836-43.
PubMed 8196140Cohen J, Carlet J. INTERSEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis. International Sepsis Trial Study Group. Crit Care Med. 1996 Sep;24(9):1431-40. doi: 10.1097/00003246-199609000-00002.
PubMed 8797612Abraham E, Reinhart K, Opal S, Demeyer I, Doig C, Rodriguez AL, Beale R, Svoboda P, Laterre PF, Simon S, Light B, Spapen H, Stone J, Seibert A, Peckelsen C, De Deyne C, Postier R, Pettila V, Sprung CL, Artigas A, Percell SR, Shu V, Zwingelstein C, Tobias J, Poole L, Stolzenbach JC, Creasey AA; OPTIMIST Trial Study Group. Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA. 2003 Jul 9;290(2):238-47. doi: 10.1001/jama.290.2.238.
PubMed 12851279Afshari A, Wetterslev J, Brok J, Moller A. Antithrombin III in critically ill patients: systematic review with meta-analysis and trial sequential analysis. BMJ. 2007 Dec 15;335(7632):1248-51. doi: 10.1136/bmj.39398.682500.25. Epub 2007 Nov 23.
PubMed 18037615Ranieri VM, Thompson BT, Barie PS, Dhainaut JF, Douglas IS, Finfer S, Gardlund B, Marshall JC, Rhodes A, Artigas A, Payen D, Tenhunen J, Al-Khalidi HR, Thompson V, Janes J, Macias WL, Vangerow B, Williams MD; PROWESS-SHOCK Study Group. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med. 2012 May 31;366(22):2055-64. doi: 10.1056/NEJMoa1202290. Epub 2012 May 22.
PubMed 22616830Santacruz CA, Pereira AJ, Celis E, Vincent JL. Which Multicenter Randomized Controlled Trials in Critical Care Medicine Have Shown Reduced Mortality? A Systematic Review. Crit Care Med. 2019 Dec;47(12):1680-1691. doi: 10.1097/CCM.0000000000004000.
PubMed 31567349Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18.
PubMed 28101605van der Meche FG, Schmitz PI. A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain-Barre syndrome. Dutch Guillain-Barre Study Group. N Engl J Med. 1992 Apr 23;326(17):1123-9. doi: 10.1056/NEJM199204233261705.
PubMed 1552913Barth D, Nabavi Nouri M, Ng E, Nwe P, Bril V. Comparison of IVIg and PLEX in patients with myasthenia gravis. Neurology. 2011 Jun 7;76(23):2017-23. doi: 10.1212/WNL.0b013e31821e5505. Epub 2011 May 11.
PubMed 21562253Mandawat A, Kaminski HJ, Cutter G, Katirji B, Alshekhlee A. Comparative analysis of therapeutic options used for myasthenia gravis. Ann Neurol. 2010 Dec;68(6):797-805. doi: 10.1002/ana.22139.
PubMed 21061395Bonnan M, Cabre P. Plasma exchange in severe attacks of neuromyelitis optica. Mult Scler Int. 2012;2012:787630. doi: 10.1155/2012/787630. Epub 2012 Feb 12.
PubMed 22474589DeSena AD, Noland DK, Matevosyan K, King K, Phillips L, Qureshi SS, Greenberg BM, Graves D. Intravenous methylprednisolone versus therapeutic plasma exchange for treatment of anti-N-methyl-D-aspartate receptor antibody encephalitis: A retrospective review. J Clin Apher. 2015 Aug;30(4):212-6. doi: 10.1002/jca.21363. Epub 2015 Feb 9.
PubMed 25664728
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PILOT STUDY in the Use of Therapeutic Plasma Exchange in Adult Patients With Severe Sepsis
- ClinicalTrials.gov ID
- NCT04057872
- Acronym / sponsor ID
- REB19-1157
- Conditions
- Septic Shock
- Keywords
- Therapeutic Plasma Exchange (TPE), Septic Shock, Severe Sepsis, Albumin, Fresh Frozen Plasma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Alberta Health Services, CalgaryUniversity, hospital or other
- Study start
- 21 Oct 2020 (actual)
- Primary completion
- 31 Dec 2024 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 15 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The incidence of sepsis (severe infection) has increased over the last four decades. Severe sepsis and septic shock are among the leading causes of death for patients admitted to critical care units with mortality ranging from 20-70% depending on totality of organ dysfunction. Outside of antibiotics and good bedside care, little has changed in the management of this life-threatening problem.
Therapeutic plasma exchange (TPE) involves the separation of plasma from whole blood. The removed plasma is 'exchanged or replaced' with either IV fluids, albumin, blood products or a combination thereof.
The primary objective of this study is to evaluate the safety of the TPE intervention protocol within 24 hours of study criteria being met. TPE is now a well-established program at the South Health Campus for neuro-muscular disorders. Since starting in May 2018, the investigators have performed over 150 runs making the SHC ICU one of the most experienced centers in Canada.
Detailed description
Background
The incidence of sepsis has increased over the last four decades (1). Sepsis is a life-threatening condition that arises when the body's response to an infection injures its own tissues and organs. Severe sepsis and septic shock are among the leading causes of death for patients admitted to critical care units with mortality ranging from 20-70% depending on totality of organ dysfunction (2, 3). The literature is replete with initial promising phase 2 therapies failing in definitive randomized trails (4-8). In fact, a recent systematic review concluded that no evidence exists for any pharmacologic intervention that has consistently reduced mortality in critically ill patients (9). This is both surprising and frustrating for the author. The most recent guidelines have tried to redefine sepsis as a 'syndrome' since neither validated criterion nor do standard diagnostic tests exist (10). The authors argue that sepsis should be viewed as organ dysfunction caused by a dysregulated or non-homeostatic host response. Most of the clinical manifestations of severe infections are caused by an intense, generalized inflammatory response in the host mediated by a multitude of interrelated cellular and humoral factors (3).
Plasmapheresis or therapeutic plasma exchange (TPE) involves the separation of plasma from whole blood. The removed plasma is 'exchanged or replaced' with crystalloids, albumin, fresh frozen plasma or a combination thereof. TPE use is well established in many neurological disorders including Guillain-Barre syndrome (11), Myasthenia Gravis (12, 13) and antibody mediated syndromes(14, 15). It is considered the standard of care for thrombotic thrombocytopenic purpura (TTP) (16, 17). The rationale for the use of TPE in sepsis, a non-selective intervention, is to remove multiple toxic mediators including endotoxins, activated complement, pro-inflammatory cytokines and pro-coagulant factors (18, 19). If fresh-frozen plasma is used as replacement fluid, consumed plasma factors are substituted, thereby possibly restoring the opsonic capacity and improving the coagulation abnormalities and microcirculation.
Plasma exchange has been reported since the late 1970s as a potential adjunctive or salvage therapy in severe sepsis in both pediatric and adult patients (20-24). These case reports, retrospective reviews and observational studies suggest a survival advantage when compared to historical controls. However, the obvious bias limits any meaningful interpretation. A literature review found only 4 studies with any attempt at randomization. One study enrolled only adults (25), two were exclusively pediatric patients (26, 27) and one study involved both adults and children (28). Excluding the pediatric studies, the adult protocols had few similarities:
- Reeves and colleagues attempted a multi-center Australian study but terminated enrollment after 22 adult and 8 children (28). The mean APACHEII scores for adults were 25.2. They aggressively exchanged 5 plasma volumes continuously over 36 hours using a combination of fresh frozen plasma (FFP) and albumin (1/4 ratio). Mortality was reported at 14 days. No data on ICU or hospital length of stay was provided. This trial reported significant decrease in certain inflammatory markers.
- Busund's larger trail involved 106 adults and reported mortality at 28 days (25). They performed a single 30-40mls/kg exchange that could be repeated once if no clinical improvement was observed. The replacement used was FFP and albumin in a 1:1 ratio. Six episodes of transient hypotension and 1 allergic reaction to FFP was reported (the only trial to report adverse events). There was an encouraging trend towards improved survival (33% vs 53%) versus historical controls. No data on ICU or hospital length of stay was provided.
A more recent German pilot study tried to evaluate the safety and feasibility of enrollment within 12 hours of shock for a proposed randomized controlled trial (RCT) (29). The inclusion criteria were simple: (a) Current sepsis-3 definitions; noradrenaline dose >0.4ug/kg/min despite >30mls/kg of crystalloid; (b) Less than 12 hours of vasopressor support. They performed a single 1.2x plasma exchange using entirely FFP. The major findings were significantly less vasopressor support, fluid balance and a decline in plasma concentrations of pro-inflammatory mediators. The "sustained -responders" mortality was 43% vs 77% of non-responders, but the small numbers prevented statistical significance.
The use of plasma exchange in severe sepsis is graded by the American Society for Apheresis as category III with grade 2C indications, indicating that there is a lack of reliable trials to support TPE use in the condition (30). The purpose of this phase 1 clinical trial is to assess the safety of using plasma exchange in critically ill adult patients with septic shock. TPE is now a well-established program at the South Health Campus (SHC) for neuro-muscular disorders. Since starting in May 2018, we have performed over 240 runs in 43 patients making the SHC ICU the most experienced TPE center in Canada in the past 2 years. One plasma volume is currently the standard dose used safely in patients with neuro-muscular disorders at SHC.
Justification of Research
- The incidence of sepsis has increased over 4 decades but no single pharmacological invention reduces mortality/morbidity.
- A potential treatment that increases the chance of survival and recovery in patients with septic shock would be both beneficial to patients and help decrease medical costs from long term stays in the ICU.
- The maximum tolerable dose of TPE in septic patients is unknown.
Study Objectives
Primary Objective: To evaluate the safety of the TPE intervention protocol within 24 hours of study criteria being met.
Secondary Objectives:
- To evaluate preliminary efficacy of the TPE protocol.
- To determine maximum tolerable dose of TPE in septic patients.
- To record adverse events from TPE intervention.
Hypothesis
It is hypothesized that TPE will be safe for use in patients with septic shock. We will determine the maximum tolerable dose via a dose escalation study.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Consecutive Adults patients with vasoplegic septic shock with at least 2 organ dysfunction will receive TPE
| Arm | Type | Receives |
|---|---|---|
| TPE in Septic Shock | Experimental | Procedure: Therapeutic plasma exchangeThe patients will undergo a dosing trial to determine safety and the most effective dose |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Therapeutic plasma exchangeThe removed plasma is 'exchanged or replaced' with either IV fluids, albumin, and/or Fresh frozen plasma | Procedure or surgery | TPE in Septic Shock |
Primary outcome
Adverse Events
Time frame: During course of ICU stay, could be up to 6 months
Proportion of patients who experience at least 1 Adverse Event (AE)
Discontinue TPE
Time frame: During course of ICU stay, could be up to 6 months
Proportion of patients who discontinue TPE administration due to an AE
Enrollment Rate
Time frame: During course of ICU stay, could be up to 6 months
3. Enrollment rate (patients screened, patients eligible, patients approached, patients enrolled)
Protocol Completion
Time frame: During course of ICU stay, could be up to 6 months
Protocol completion (patients who complete study protocol)
6 secondary outcomes
Organ dysfunction
Time frame: During course of ICU stay, could be up to 6 months
Vasopressor support
Time frame: During course of ICU stay, could be up to 6 months
Ventilator support
Time frame: During course of ICU stay, could be up to 6 months
Days in ICU
Time frame: During course of ICU stay, could be up to 6 months
Mortality
Time frame: During course of ICU stay, could be up to 6 months
RRT Required
Time frame: During course of ICU stay, could be up to 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2025.
- Background: PubMed 12700374Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003 Apr 17;348(16):1546-54. doi: 10.1056/NEJMoa022139.
- Background: PubMed 23984731Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013 Aug 29;369(9):840-51. doi: 10.1056/NEJMra1208623. No abstract available.
- Background: PubMed 28448952Minasyan H. Sepsis and septic shock: Pathogenesis and treatment perspectives. J Crit Care. 2017 Aug;40:229-242. doi: 10.1016/j.jcrc.2017.04.015. Epub 2017 Apr 18.
- Background: PubMed 8196140Fisher CJ Jr, Dhainaut JF, Opal SM, Pribble JP, Balk RA, Slotman GJ, Iberti TJ, Rackow EC, Shapiro MJ, Greenman RL, et al. Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group. JAMA. 1994 Jun 15;271(23):1836-43.
- Background: PubMed 8797612Cohen J, Carlet J. INTERSEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis. International Sepsis Trial Study Group. Crit Care Med. 1996 Sep;24(9):1431-40. doi: 10.1097/00003246-199609000-00002.
- Background: PubMed 12851279Abraham E, Reinhart K, Opal S, Demeyer I, Doig C, Rodriguez AL, Beale R, Svoboda P, Laterre PF, Simon S, Light B, Spapen H, Stone J, Seibert A, Peckelsen C, De Deyne C, Postier R, Pettila V, Sprung CL, Artigas A, Percell SR, Shu V, Zwingelstein C, Tobias J, Poole L, Stolzenbach JC, Creasey AA; OPTIMIST Trial Study Group. Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA. 2003 Jul 9;290(2):238-47. doi: 10.1001/jama.290.2.238.
- Background: PubMed 18037615Afshari A, Wetterslev J, Brok J, Moller A. Antithrombin III in critically ill patients: systematic review with meta-analysis and trial sequential analysis. BMJ. 2007 Dec 15;335(7632):1248-51. doi: 10.1136/bmj.39398.682500.25. Epub 2007 Nov 23.
- Background: PubMed 22616830Ranieri VM, Thompson BT, Barie PS, Dhainaut JF, Douglas IS, Finfer S, Gardlund B, Marshall JC, Rhodes A, Artigas A, Payen D, Tenhunen J, Al-Khalidi HR, Thompson V, Janes J, Macias WL, Vangerow B, Williams MD; PROWESS-SHOCK Study Group. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med. 2012 May 31;366(22):2055-64. doi: 10.1056/NEJMoa1202290. Epub 2012 May 22.
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- Individual participant dataSharing planned: Yes. Once the results have been analyzed and published the de-identified data will be made available to other researchers
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
George F Alvarez, MD principal investigator
Alberta Health services
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Therapeutic plasma exchange in people with Septic Shock, run by Alberta Health Services, Calgary at 2 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: finished, as of the sponsor's last update on 3 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (time frame: During course of ICU stay, could be up to 6 months). The study lists 4 primary outcomes in all. 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 NCT04057872, which also lists 30 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 3 Oct 2025.