Therapeutic Plasma Exchange in Septic Shock: A Pilot Study
- Conditions
- Septic Shock
- Registration Number
- NCT05093075
- Lead Sponsor
- University of Manitoba
- 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.
- 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).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 80
Not provided
Patients who have any one of the following criteria at the time of enrollment will be excluded:
- Consent declined (refusal from patient, SDM, or physician)
- Clinically apparent alternate causes for shock (cardiogenic, hemorrhagic, obstructive, neurogenic or anaphylactic)
- Received vasopressor therapy for greater than 24 hours prior to enrollment
- Terminal illness with a life expectancy of less than 3 months
- Are pregnant
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Assess the feasibility of a large, multicenter trial of TPE in patients with septic shock 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.
- Secondary Outcome Measures
Name Time Method Assess the rate of enrollment and adherence to the protocol of those enrolled 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.
Further understand the biological impact of TPE in sepsis 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.
Number of participants that develop adverse reactions to TPE 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.