Use of Inhaled High-molecular Weight Hyaluronan in Patients With Severe COVID19: Feasibility and Outcomes (HA-COVID)

To determine whether inhaled Yabro protects against progression of COVID19-induced respiratory failure preventing the passage to non-invasive ventilation (NIV) and promotes recovery from COVID19 lung disease in hospitalized patients.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: HMW-HA

Detailed Description

All patients will be treated with state of the art COVID19 treatment as per the treating clinician (Remdesivir, systemic corticosteroids, monoclonal antibodies, convalescent plasma, biologic cytokine inhibitors and other interventions as per the latest guidelines). Patients randomized to the active intervention group will also receive HMW-HA (Yabro®, 5 ml of saline containing 0.3% hyaluronic acid sodium salt) via nebulizer, while patients randomized in the control group will receive a matching placebo two times daily.

Due to increased risk for SARS-CoV-2 transmission via the usual mask nebulization procedure, patients will receive the nebulized treatment via high-flow oxygen tubing as described in the literature 36-38. Patients will be treated until there is a qualitative change in oxygen requirement, i.e. either progression to assisted ventilation (non-invasive or invasive), or weaning from oxygen supplementation. Because COVID19 may result in long-term O2 dependency, the study and treatment period will be limited to a maximum of 10 days.

Moreover, a blood sample (20 ml) will be taken at baseline and after 10 days of treatment.

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy, 00128
    • Università Campus Biomedico di Roma

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:

• Age ≥ 18
• Diagnosis of COVID19 by validated SARS-CoV-2 antigen, RT-PCR, or other molecular diagnostic assay, using an appropriate sample such as NP, nasal, oropharyngeal [OP], or saliva) and no alternative explanation for current clinical condition.
• Respiratory failure requiring oxygen therapy
• Has symptoms consistent with COVID-19, and is in non-fibroproliferative stage of disease, as determined by investigator.

Exclusion Criteria:

• Respiratory arrest or the need for immediate intubation;
• Upper airway obstruction;
• Facial trauma;
• Inability to cooperate (e.g. agitation or dementia)
• Inability to give informed consent
• Participation in another study for COVID19 treatments
• Deterioration due to other reasons than progressive COVID19 pneumonia per clinical judgment, e.g. pulmonary thromboembolism, heart failure, renal failure etc.
• Palliative care or expectation that patient will not survive > 72 hours post randomization per clinical judgment of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: HMW-HA; HMW-HA (Yabro - 5 ml of saline containing 0.3% hyaluronic acid sodium salt)	Drug: HMW-HA; Aerolized administration b.i.d.; Other Names: Yabro
Placebo Comparator: placebo; 5 ml of saline via nebulizer b.i.d.	Drug: HMW-HA; Aerolized administration b.i.d.; Other Names: Yabro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative time on oxygen	cumulative duration of oxygen treatment	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for advanced airway intervention or death due to COVID19;	need of intubation or death due to COVID19	10 days
Rate of change of respiratory rate;	rapidity of decrease of respiratory rate	10 days
Change in PaO2 /FiO2 ratio during treatment	improvement of PaO2/FiO2 ratio after 10 days of treatment	10 days
Time to discharge from hospital	decrease of cumulative days of hospitalization	10 days

Collaborators and Investigators

• Sponsor: Campus Bio-Medico University
• Collaborators: National Institute of Environmental Health Sciences (NIEHS)
• Investigators: Principal Investigator: Raffaele Antonelli Incalzi, MD, Università Campus-Biomedico di Roma

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2021
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): September 30, 2021

Study Registration Dates

• First Submitted: March 31, 2021
• First Submitted That Met QC Criteria: March 31, 2021
• First Posted (Actual): April 2, 2021

Study Record Updates

• Last Update Posted (Actual): March 16, 2022
• Last Update Submitted That Met QC Criteria: March 1, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: 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
• Other Study ID Numbers: CampusBioMedico; 1ZIDES102465 (U.S. NIH Grant/Contract)

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