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

University of Manitoba

Status and phase: Enrolling; Phase 2

Conditions: Septic Shock

Treatments: Other: Therapeutic Plasma Exchange

Study type: Interventional

Funder types: Other

Identifiers

NCT05093075

HS23165 (B2019:093)

Details and patient eligibility

About

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.

Full 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).

Enrollment: 80 estimated patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

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

4. Known or suspected infection

Exclusion Criteria:

Patients who have any one of the following criteria at the time of enrollment will be excluded:

1. Consent declined (refusal from patient, SDM, or physician)
2. Clinically apparent alternate causes for shock (cardiogenic, hemorrhagic, obstructive, neurogenic or anaphylactic)
3. Received vasopressor therapy for greater than 24 hours prior to enrollment
4. Terminal illness with a life expectancy of less than 3 months
5. Are pregnant

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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80 participants in 2 patient groups

Treatment Arm

Experimental group

Description:

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.

Treatment:

Other: Therapeutic Plasma Exchange

Standard of Care Arm

No Intervention group

Description:

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.