Personalized Targeted Immunomodulation in COVID-19 ARDS (COMODULATE)

Personalized Targeted Immunomodulation in Patients With ARDS Related to COVID19 and Future Pandemic Pathogens

Rationale: In COVID19 single-targeted immunomodulation, mostly via an IL-6 receptor blocker, was used by a one-size fits all non-targeted approach. In future pandemics the same might occur. However, for individual patients, this might not yield optimal treatment.

Objectives: This project aims to identify a way to individualize and target immunomodulation, using COVID19 as a testcase for the future.

• Identify immunological pathways which are associated with outcome in C-ARDS.
• Test whether an individualized biomarker-based approach has an effect on outcome and costs when using single-target immunomodulation in C-ARDS(Tocilizumab, Anakinra, etc.).
• Explore whether other immunological pathways were present in patients with C-ARDS which could have been intervened with medication which is already available and has been described in ARDS or similar diseases.

Study type: Retrospective observational multicenter study in the Netherlands.

Study population: Adult patients (≥ 18 years) hospitalized and admitted to the ICU with COVID-19 and acute respiratory distress syndrome (ARDS) (i.e., receiving invasive mechanical ventilation) will be included.

Intervention (if applicable): Not applicable (retrospective study design).

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Given the retrospective nature of the study, no burden, risks or benefits for the patient are associated with participation. The target population of this study is specific to hospitalized patients with COVID-19.

Study Overview

• Status: Completed
• Conditions: COVID-19 Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: Single target immunomodulation; Drug: Standard of care

• Study Type: Observational
• Enrollment (Actual): 164

Contacts and Locations

Study Locations

• Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015 GD
      • Erasmus Medical Centre

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Adults aged 18 years or older, admitted to the ICU due to COVID-induced moderate or severe ARDS as defined by the Berlin criteria, and requiring mechanical ventilation, were eligible for study participation.

Description

Inclusion Criteria:

• At least 18 years of age
• Admitted to ICU due to COVID induced moderate or severe ARDS
• Requiring mechanical ventilation

Exclusion Criteria:

- Refusing participation

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Treated with immunomodulation; Adult patients with COVID-19 ARDS admitted to ICU and requiring mechanical ventilation and receiving standard of care treatment (including steroids) and single-target immunomodulation, for example Toculizimab, Anakinra, etc.	Drug: Single target immunomodulation; Single target immunomodulation compromise of drugs which very specifically target cytokines, chemokines or specific receptors, which are involved in the pathofysiology of COVID-19. For instance, tociluzimab (IL-6 receptor blocker), Anakinra (IL-1 receptor blocker), Eculizimab (Complement inhibitor C5), etc.
Not treated with immunomodulation; Adult patients with COVID-19 ARDS admitted to ICU and requiring mechanical ventilation and receiving standard of care treatment (including steroids).	Drug: Standard of care; Standard of care during COVID-19 pandemic including steroids.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality up to day 90		From date of ICU admission up to date of hospital discharge, assessed up to 90 days.
Change in SOFA score	Repeated measurements of SOFA scores during ICU admission will be performed on days 0, 1, 2, 7, 14, 21 and 28. SOFA scores will be compared between days and from the start to the end of ICU admission.	During the full course of ICU-admission. The length of ICU-stays varies per patient.
Ventilator free days	Number of ventilator free days	During the full course of ICU admission. The length of ICU-stays varies per patient.
Change in biomarker values	Repeated measurements of biomarkers during ICU admission will be performed on days 0, 1, 2, 7, 14, 21 and 28. Biomarker values will be compared between days and from the start to the end of ICU-admission.	During the full course of ICU admission. The length of ICU-stays varies per patient.
Costs of immmunomodulation	Costs of immunomodulation will be compared to the costs of dexamethason. Furthermore, we will explore whether patients who were treated with single target immunomodulation have shorter ICU length of stay and more ventilator free days, which also reduce the total costs.	During the full course of ICU admission. The length of ICU-stays varies per patient.

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: St. Antonius Hospital; Leiden University Medical Center; Amsterdam UMC
• Investigators: Principal Investigator: H. Endeman, Dr., Erasmus Medical Centre

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2020
• Primary Completion (Actual): February 1, 2022
• Study Completion (Actual): February 1, 2022

Study Registration Dates

• First Submitted: March 8, 2024
• First Submitted That Met QC Criteria: March 13, 2024
• First Posted (Actual): March 15, 2024

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Biomarker; Immunomodulation; JAK inhibitors; IL-1 inhibitors; Tociluzimab; Complement inhibitors; IL-6 inhibitors
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: 10094

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be made available through a secure data transfer system and appropriate data transfer agreement. (The data set contains personal data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No