Mesenchymal Stem Cells (MSCs) in Inflammation-Resolution Programs of Coronavirus Disease 2019 (COVID-19) Induced Acute Respiratory Distress Syndrome (ARDS)

Prospective Phase II Study: MSCs in Inflammation-Resolution Programs of SARS-CoV-2 Induced ARDS

To evaluate the safety, toxicity and immunological effects of infusion of allogeneic bone marrow-derived human mesenchymal stem (stromal) cells (MSCs) and whether this therapy has an influence on the resolution processes in ARDS patients infected with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Study Overview

• Status: Not yet recruiting
• Conditions: COVID-19; ARDS
• Intervention / Treatment: Biological: MSC

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Tuebingen, Germany, 72076
    • University Hospital Tuebingen
    • Contact: Peter Rosenberger, MD
    • Principal Investigator: Peter Rosenberger, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• COVID-19-positive subject
• Horowitz index ≤ 200
• Bilateral opacities on frontal chest radiograph, and
• requirement for positive pressure ventilation via an endotracheal tube or non-invasive ventilation
• no clinical signs of left atrial hypertension detected via echocardiography, or if measured, a Pulmonary Arterial Wedge Pressure (PAOP) less than or equal to 18 mmHg.
• Subject's Age ≥ 18 years

Exclusion Criteria:

• COVID-19-negative subject
• Subject's Age < 18 years
• More than 7 days since initiation of mechanical ventilation
• Patient, surrogate or physician not committed to full intensive care support.
• Positive Pregnancy test at the time of screening.
• Patients dependent on the sponsor, investigator and their employees, as well as persons dependent on the manufacturer of the investigational drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: control
EXPERIMENTAL: MSC Treatment	Biological: MSC; infusion of allogeneic bone marrow-derived human mesenchymal stem (stromal) cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
lung injury score	improvement of lung injury score (LIS), 0-16 points, severity increasing with higher points	day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
D-dimers	D-dimers blood levels	day 0, 1, 2, 3, 10 and 15
phenotype	distribution of phenotypes of immune cells	day 0, 1, 2, 3, 10 and 15
pro-resolving lipid mediators	Levels of specialized pro-resolving lipid mediators within alveolar macrophages and bronchoalveolar lavage	day 0, 1, 2, 3, 10 and 15
cytokines	Cytokine concentration within bronchoalveolar lavage and Serum prior and after MSC infusions	day 0, 1, 2, 3, 10 and 15
chemokines	Chemokine concentration within bronchoalveolar lavage and Serum prior and after MSC infusions	day 0, 1, 2, 3, 10 and 15
Survival	Survival at 10 days and 28 days	day 10 and 28
extubation	Time to removal of endotracheal tube	day 28
lymphocyte subpopulations	lymphocyte subpopulations in peripheral blood by flow cytometry prior and after MSC infusion (day 0,3,5,10)	day 0, 3, 5 and 10
SARS-CoV-2-specific antibody titers	evaluate SARS-CoV-2-specific antibody titers in the serum of patients prior and post MSC infusion.	day 0, 5 and 10
complement molecules (C5-C9)	evaluate levels of complement molecules (C5-C9) in the serum of patients prior and post MSC infusion	day 0, 5 and 10

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 1, 2022
• Primary Completion (ANTICIPATED): November 1, 2022
• Study Completion (ANTICIPATED): February 1, 2023

Study Registration Dates

• First Submitted: April 16, 2020
• First Submitted That Met QC Criteria: May 4, 2020
• First Posted (ACTUAL): May 6, 2020

Study Record Updates

• Last Update Posted (ACTUAL): January 27, 2022
• Last Update Submitted That Met QC Criteria: January 26, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Inflammation
• Other Study ID Numbers: RESCOVID

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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