Modulation of Hyperinflammation in COVID-19

Lawson Health Research Institute

Status: Completed

Conditions: COVID-19; SARS

Treatments: Device: SLEDD with a L-MOD; Device: Control group

Study type: Interventional

Funder types: Other

Identifiers

NCT04353674

115785

Details and patient eligibility

About

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.

Full 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.

Enrollment: 12 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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12 participants in 2 patient groups

Control

Sham Comparator group

Description:

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

Treatment:

Device: Control group

SLEDD with a L-MOD

Active Comparator group

Description:

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.

Treatment:

Device: SLEDD with a L-MOD