Evaluation of Hemodynamic Effects of Cascade Hemofiltration in Septic Shock (Cascade)

Septic shock is a major cause of mortality and morbidity in critically ill patients. Septic Shock is associated with an overwhelming, systemic overflow of pro inflammatory and anti-inflammatory mediators, which leads to generalized endothelial damage, multiple organ failure, and altered cellular immunological responsiveness. Although our understanding of the complex pathophysiological alterations that occur in septic shock has increased greatly as a result of recent clinical and preclinical studies, mortality associated with the disorder remains unacceptably high, ranging from 30% to 50%. To date, attempts to improve survival with innovative, predominantly anti-inflammatory therapeutic strategies have been disappointing. A standard hemofiltration rate of 35 ml/kg/hour has been successfully used to treat acute renal failure. However, this dose does not alter plasma levels of inflammatory mediators, suggesting that its ability to clear these mediators is suboptimal. Higher doses of hemofiltration (up to 120 ml/kg per hour) have been demonstrated to improve cardiac function and hemodynamics in several animal models of sepsis. High-volume hemofiltration (HVHF) was thus conceived and applied in patients with septic shock, showing an improvements in hemodynamics with decreased vasopressor requirements and improved survival in patients admitted after a cardiac arrest.

The main benefit described with high volume hemofiltration is a hemodynamic improvement (e.g reduction in catecholamines' requirement). This improvement seems to be due to the removal of a badly defined network of middle molecular weight peptides. To remove efficiently these middle molecular peptides, a high filtration rate is needed. However, with high filtration rates, there is also a high clearance for smaller molecules, including antibiotics, electrolytes, vitamins, trace elements and amino acids.

The cascade hemofiltration system has been designed for a more efficient removal of middle molecular weight peptides with a limited solute consumption.

The goal of this study is the evaluation of the hemodynamic improvement using cascade hemofiltration in patients treated for septic shock.

Study Overview

• Status: Completed
• Conditions: Sepsis
• Intervention / Treatment: Other: Standard treatment; Device: Cascade

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63003
    • CHU hospital
  • Dijon, France, 21079
    • Hôpital Le Bocage
  • Melun, France, 77 000
    • Centre Hospitalier Marc Jacquet
  • Paris, France, 75020
    • Hopital Tenon
  • Saint Denis, France, 93205
    • Hôpital Delafontaine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient with a septic shock diagnosed by the medical staff team.
• Patient mechanically ventilated and treated by high doses of catecholamines after adequate fluid administration (≥ 1.0 mg/h of norepinephrine or epinephrine) for ≥ 120 minutes and < 24h.

Exclusion Criteria:

• Age (years) < 18 or > 85.
• Weight >120 kg
• Thrombocytopenia 50< G/l or Neutrophils <0.5 Giga/l
• Contra indication to heparin anticoagulation.
• Patient requiring catecholamines (epinephrine ≥ 1 mg/h or norepinephrine ≥ 1 mg/h) for >24h.
• Patient admitted to the ICU ≥ 7 days before the inclusion criteria.
• Comorbid conditions with an expected survival < 6 months
• Inclusion (<28 days) in another study interfering with the goals of the current investigation.
• Pregnancy
• Immune compromised patients (e.g. being treated for cancer, treated by immunosuppressors or steroids, AIDS).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard treatment	Other: Standard treatment; Standard therapy
Experimental: Cascade	Device: Cascade; Cascade treatment over 48h

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the primary outcome will be the number of days without catecholamines at the 28th day of randomization	28th day

Secondary Outcome Measures

Outcome Measure	Time Frame
rate of decrease of catecholamines during the first 72h, days without mechanical ventilation at D90, days without RRT for acute renal failure at D90, days without ICU requirement at D90, status at D90.	72h, D90

Collaborators and Investigators

• Sponsor: Baxter Healthcare Corporation
• Collaborators: Gambro Lundia AB
• Investigators: Study Chair: Monchi Mehran, Dr, Unaffiliate

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: June 15, 2009
• First Submitted That Met QC Criteria: June 16, 2009
• First Posted (Estimate): June 17, 2009

Study Record Updates

• Last Update Posted (Actual): April 5, 2017
• Last Update Submitted That Met QC Criteria: April 4, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Sepsis; Shock, Septic
• Other Study ID Numbers: 1450