Modulation of Hyperinflammation in COVID-19

March 28, 2024 updated by: Chris McIntyre, Lawson Health Research Institute

Novel Extracorporeal Treatment to Modulate Hyperinflammation in COVID-19 Patients

Current treatment recommendations are based on very limited evidence and reliant on the deployment of pharmacological strategies of doubtful efficacy, high toxicity, and near universal shortages of supply. On a global scale, there is a desperate need for readily available therapeutic options to safely and cost effectively target the hyper-inflammatory state in ICU patients based on management of severe COVID-19 (evidence of acute respiratory distress syndrome). The study team proposes to use slow low-efficiency daily dialysis to provide an extracorporeal circuit to target this cytokine storm using immunomodulation of neutrophils with a novel leucocyte modulatory device (L-MOD) to generate an anti-inflammatory phenotype, but without depletion of circulating factors.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The coronavirus disease 2019 (COVID-19) is a novel virus that was first reported in December 2019 from Wuhan, China. So far, over 8,000,000 cases have been reported around the globe with >400,000 reported deaths overwhelming hospitals and constraining resources. Death is mainly due to severe acute respiratory syndrome (SARS), requiring mechanical ventilation; however, many hospitals do not have sufficient equipment (i.e. ventilators) to meet the requirements. It had been suggested that severe SARS-related injury may have be related to an excessive reaction of the host's immune system, and a dysregulation of pro-inflammatory cytokines called cytokine storm syndrome. This is characterized by a hyper-inflammatory state leading to fulminant multi-organ failure and elevated cytokine levels. There is a critical and imminent need to identify effective treatments to reduce mortality.

The study team proposes to use slow low-efficiency daily dialysis (SLEDD) to provide an extracorporeal circuit to target this cytokine storm using immunomodulation of neutrophils with a novel leukocyte modulatory device (L-MOD) to generate an anti-inflammatory phenotype, without depletion of circulating factors.

This is a single center, prospective, randomized controlled pilot study in the Critical Care Trauma Centre at Victoria Hospital and Critical Care at University Hospital, London, Ontario. Critical Care at University Hospital is comprised of two units, the Medical-Surgical ICU and the Cardiac Surgical Recovery Unit. The study team will randomize patients requiring ICU admission of COVID-19 into one of two groups; either to standard of care for severe COVID-19 infection or in the active treatment group (standard supportive care + treatment with leukocyte modulation (using L-MOD)), on 1:1, basis. They will know what treatment group they are randomized to.

The study team will use block randomization to randomize the patients into one of these two groups. A computer algorithm is used to generate the randomization sequence in blocks of four (two for standard of care and two for active treatment). This is used to make sure that equal numbers of people get allocated to each arm of the study and that the allocation is equal throughout the lifespan of the trial.

Slow low-efficiency daily dialysis will be performed twice, for approximately 12 hours, 2 days in a row. Due to the nature of the intervention, it is not possible to blind neither the patient nor study team members to the treatment group the patient gets randomized to, with the exception of study team members analyzing the data who will be blinded to the patients' treatment group. Additionally, the study uses robust objective measurements that will be unaffected by the patients' awareness of the group they have been randomized to.

Blood work will be collected before each dialysis treatment initiation, at the end of each session, and then on after day 4 and no later than day 7 in the ICU for the patients receiving intervention. Patients receiving standard of care will have blood work done on day 1, day 2, and after day 4 and no later than day 7 of admission. We will also collect a urine sample from all participants before the first dialysis session only and then again at after day 4 and no later than day 7 in the ICU. End of study will be defined as the last patient discharged from the hospital.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • London, Ontario, Canada, N6A 5A5
        • University Hospital
      • London, Ontario, Canada, N6C 2V4
        • Victoria Hospital - Critical Care Trauma Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age greater than or equal to 18 years
  • High clinical suspicion of COVID-19 from the opinion of both infectious disease specialist (s) and the ICU team
  • Evidence of acute respiratory distress syndrome requiring admission to the Critical Care Trauma Centre Medical Surgical ICU, or the Cardiac Surgical Recovery Unit
  • Vasopressor support

Exclusion Criteria:

  • Pregnant
  • Unconfirmed COVID-19
  • Chronic immune depression
  • Contra-indications to regional citrate anticoagulation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Sham Comparator: Control
Patients diagnosed with severe COVID-19: Those admitted to the intensive care unit with evidence of severe respiratory distress syndrome will undergo standard of care
Device: Control group
Patients randomized into this group will receive standard of care for COVID-19 infection
Active Comparator: SLEDD with a L-MOD
Patients diagnosed with severe COVID-19: Those admitted to the intensive care unit with evidence of severe respiratory distress syndrome will undergo slow low efficiency daily dialysis for approximately 12 hours, 2 days in a row with a leukocyte modulatory device.
Device: SLEDD with a L-MOD
Patients randomized to this group will undergo slow low efficiency daily dialysis for approximately 12 hours, 2 days in a row with a leukocyte modulatory device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of a L-MOD against controls receiving supportive care in ICU.
Time Frame: Through dialysis, on average of 12 hours, two days in a row
Efficacy will be evaluated by reduction of vasopressor support (converted to norepinephrine dose equivalents) compared to control group.
Through dialysis, on average of 12 hours, two days in a row

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 2 months
Time to ICU and hospital discharge compared to case-matched controls
From date of randomization until the date of death from any cause, whichever came first, assessed up to 2 months
Hospital Discharge
Time Frame: From date of randomization until the date of hospital discharge or death from any cause, whichever came first, assessed up to 2 months
Time to ICU and hospital discharge compared to case-matched controls
From date of randomization until the date of hospital discharge or death from any cause, whichever came first, assessed up to 2 months
Leukocyte Monitoring
Time Frame: Through dialysis, on average of 12 hours, two days in a row and again on day 5 in the ICU
Over the course of the disease white blood cells will be monitored (i.e. neutrophils, macrophages...)
Through dialysis, on average of 12 hours, two days in a row and again on day 5 in the ICU
Sequential Organ Failure Assessment (SOFA) Score
Time Frame: From date of randomization until the date of ICU discharge or death from any cause, whichever came first, assessed up to 1 months
Evolution of the Sequential Organ Failure Assessment (SOFA) score. The SOFA score ranges from 0 to 24. The higher score means the worst outcome.
From date of randomization until the date of ICU discharge or death from any cause, whichever came first, assessed up to 1 months
Intubation length
Time Frame: From date of randomization until the date of ICU discharge up to 2 months
intubation length will be recorded (in day)
From date of randomization until the date of ICU discharge up to 2 months
Markers of Inflammation
Time Frame: Through dialysis, on average of 12 hours, two days in a row and again after day 4 and no later than day 7 in the ICU
Evolution of hsCRP during dialysis treatment
Through dialysis, on average of 12 hours, two days in a row and again after day 4 and no later than day 7 in the ICU
Leukocytes and Macrophages
Time Frame: Through dialysis, on average of 12 hours, two days in a row and again after day 4 and no later than day 7 in the ICU
Characterization of activated/desactivated leukocyte and macrophage subsets in the blood
Through dialysis, on average of 12 hours, two days in a row and again after day 4 and no later than day 7 in the ICU
Myocardial damage
Time Frame: From date of randomization until the date of ICU discharge up to 2 months
Myocardial damage will be assessed by troponin measurement (ng/mL)
From date of randomization until the date of ICU discharge up to 2 months
Renal recovery
Time Frame: From date of randomization until the date of ICU discharge up to 2 months
Renal recovery will be assessed by serum creatinin measurement (micromol/L)
From date of randomization until the date of ICU discharge up to 2 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lawson Health Research Institute

Investigators

  • Principal Investigator: Christopher W McIntyre, MD, Western University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 28, 2020

Primary Completion (Actual)

December 30, 2023

Study Completion (Actual)

March 15, 2024

Study Registration Dates

First Submitted

April 7, 2020

First Submitted That Met QC Criteria

April 16, 2020

First Posted (Actual)

April 20, 2020

Study Record Updates

Last Update Posted (Actual)

March 29, 2024

Last Update Submitted That Met QC Criteria

March 28, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 115785

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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