Hemadsorption to Enhance Drug Elimination in Intoxications (MATRIX)

In this trial the investigators assess the effectiveness of applying a hemadsorber (cytosorb®) in removing benzodiazepines or tricyclic antidepressants in intoxicated patients admitted to ICU with prolonged impaired consciousness. This is a one arm interventional investigation where a hemadsorption filter is applied in patients fulfilling inclusion criteria 8 hours after admission. Plasma titer of the neurodepressing drug will be collected sequentially both before and after start of hemadsorption to evaluate the speed of drug elimination before and after application of a hemadsorption filter. Pre- and post filter titers will be obtained to evaluate adsorbability and to evaluate time to saturation of the filter.

Study Overview

• Status: Recruiting
• Conditions: Intoxication by Drug
• Intervention / Treatment: Device: Hemadsorption filter

Detailed Description

In this prospective interventional study with medical device, the investigotors would include 18 patients admitted to ICU after an intoxication with a quantifiable neurodepressing drugs (type benzodiazepines or tricyclic antidepressants) and with impaired consciousness defined as need for intubation or need for Flumazenil to prevent intubation. Naloxone is administered per standard of care to identify if opioid intoxications is the main reason of neurodepression. Patients requiring mechanical ventilation for other reasons than impaired consciousness due to this intoxication or indication for prolonged use of sedatives are excluded.

Patients with at least one risk factor for delayed drug elimination (Chronic kidney disease G3b or CHILD-Pugh B or C) and persisting impaired consciousness after eight hours (including patients with persisting need for flumazenil) and having 5 plasma titers of the neurodepressing drug with intervals of 2 hours will be initiated on a hemadsorption filter after contact between the treating team and either dr. Michaël Mekeirele or dr. Tim Balthazar to verify inclusion criteria. Patients fulfilling inclusion criteria but lacking the 5 plasma titers will get additional plasma titers with intervals of 2 hours until 5 plasma titers are obtained. If these patients still fulfill inclusion criteria at that time then a hemadosorption filter will be initiated.

After starting hemadsorption a plasma titer pre- and post filter will be obtained after 15 minutes and every 4 hours after starting hemadsorption for the first 24 hours. After this timepoint additional plasma titers will be obtained every 24 hours until stopping hemadsorption or normalisation of the plasma titer.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marie-Claire vanmalderen, Study coordinator; Phone Number: 0032 24 76 31 10; Email: Marieclaire.vanmalderen@uzbrussel.be
• Study Contact Backup: Name: Merel Stevens, Study coordinator; Phone Number: 0032 24 76 30 96; Email: Merel.stevens@uzbrussel.be

Study Locations

• Belgium
  • Brussels hoofdstedelijk gewest
    • Brussel, Brussels hoofdstedelijk gewest, Belgium, 1090
      • Recruiting
      • Universitair Ziekenhuis Brussel
      • Contact: Marie-Claire Van Malderen, Study nurse; Phone Number: 00324763110; Email: marie-claire.vanmalderen@uzbrussel.be
      • Contact: Merel Stevens, Study Nurse; Phone Number: 00324763096; Email: merel.stevens@uzbrussel.be
      • Principal Investigator: Michaël Mekeirele, Medical Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. older than18 years
2. Admission to ICU
3. GCS < 8 or requiring Flumazenil 8 hours after hospital admission
4. Having an intoxication with a benzodiazepine or tricyclic antidepressant that we can measure/quantify
5. Having a risk factor for delayed drug elimination defined as either Cirrhosis CHILD B/C or chronic kidney insufficiency KDIGO 3b or worse

Exclusion Criteria:

1. Pregnant patient
2. Patients in chronic dialysis before admission
3. Need for mechanical ventilation for other reasons than intoxications (e.g. pneumonia, neurotrauma)
4. Concomitant pathology requiring continued intravenous sedation
5. Known history of seizures
6. Contra-indication to heparin use
7. DNR restricting the use of mechanical ventilation or dialysis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hemadsorption; Hemadsorption via a dialysis catheter will be performed in patients who are unconscious due to an intoxication with quantifiable benzodiazepines or tricyclic antidepressants 8 hours after admission. Before and after application fo this hemadsorption filter plasma titers of this drug will be obtained. After application of the hemadsorption filter pre- and post-filter titers will be obtained.

Device: Hemadsorption filter; Plasma titers neurodepressing drug: At admission to the hospital (standard of care); 2 hours after admission (+/- 15 minutes); 4 hours after admission (+/- 15 minutes); 6 hours after admission (+/- 15 minutes); 8 hours after admission (+/- 15 minutes); Just before start hemadsorption Hemadsorption via dialysis catheter in patients still fulfilling inclusion criteria 8 hours after admission. Subsequent plasma titers pre- and post-hemadosorption filter: 15 minutes after start of hemadsorption (+ 15 minutes); 4 hours after start of hemadsorption (+/- 15 minutes); 8 hours after start of hemadsorption (+/- 15 minutes); 12 hours after start of hemadsorption (+/- 15 minutes); 16 hours after start of hemadsorption (+/- 15 minutes); 20 hours after start of hemadsorption (+/- 15 minutes); 24 hours after start of hemadsorption (+/- 15 minutes); Every other 24 hours until cessation of hemadsorption or normalization of the plasma titer (+/- 15 minutes)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in time to upper limit of normal of the dosed drug with versus without hemadsorption	Based on plasma titers before start of hemadsorption the half life of the drug can be calculated. A theoretical intersection with the upper boundary of normal of the intoxicated drug plasma titer can be calculated. This will be statistically compared to the real time of attaining this titer after start of hemadsorption.	From enrollment to the end of treatment (cesation hemadsorption) +/- 3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adsorbability of the individual neurodepressing drugs	Comparing the pre- and post filter titer of the neurodepressing drug the adsorbability can be observed.	From enrollment to the end of treatment (cesation hemadsorption) +/- 3 days
Time to saturation of hemadsorption filter	Comparing the pre- and post filter titer of the neurodepressing drug the time to saturation can be observed	From enrollment to the end of treatment (cesation hemadsorption) +/- 3 days
Catheter related complications	Catheter related complications (eg bleeding, infection) will be noted	From enrollment to the removal of the dialysis catheter +/- 3 days
Seizures during hemadsorption therapy	Seizures during hemadsorption therapy will be noted	From enrollment to the end of treatment (cesation hemadsorption) +/- 3 days
Bleeding during hemadsorption therapy	Bleeding during hemadsorption therapy will be noted	From enrollment to the end of treatment (cesation hemadsorption) +/- 3 days
Cost effectiveness of applying a Cytosorb® hemadsorption filter	Duration of ICU stay, duration of ventilation, cost of a hemadsorption filter and disposables amongst others will be used for an evaluation of cost effectiveness	From enrollment to discharge from ICU (+/- 1 week)
Duration mechanical ventilation	Time to extubation and stop of flumazenil will be noted	From enrollment to extubation (+/- 3 days)
Duration ICU stay	Time to discharge will be noted	From enrollment to discharge from ICU (+/- 1 week)
Need and duration vasopressors	Time untill discontinuation of vasopressors will be noted	From enrollment to stop of vasopressors (+/- 3 days)

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel
• Investigators: Principal Investigator: Michaël Mekeirele, Medical Doctor, Universitair Ziekenhuis Brussel

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: April 2, 2025
• First Submitted That Met QC Criteria: April 3, 2025
• First Posted (Actual): April 10, 2025

Study Record Updates

• Last Update Posted (Actual): May 15, 2025
• Last Update Submitted That Met QC Criteria: May 12, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Benzodiazepine; Intoxication; Hemadsorption; Tricyclic antidepressant
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Poisoning
• Other Study ID Numbers: CIV-24-12-050174

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Single center study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No