HiFlo-COVID: High-Flow Nasal Cannula in Severe COVID-19 With Acute Hypoxemic Respiratory Failure.

Sponsor

Fundacion Clinica Valle del Lili (Other)

Overall Status

Completed

CT.gov ID

NCT04609462

Collaborator

(none)

199

Enrollment

Location

Arms

Actual Duration (Months)

33.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This open label randomized controlled multicenter phase II trial will evaluate the clinical impact of the use of HFNC vs. conventional oxygen therapy in patients with moderate and severe hypoxemic acute respiratory failure secondary to SARS-CoV-2 infection.

Condition or Disease	Intervention/Treatment	Phase
Covid19 Acute Hypoxemic Respiratory Failure	Procedure: Conventional oxygen therapy Procedure: High flow nasal cannula	N/A

Detailed Description

Acute hypoxemic respiratory failure is a condition in which rapid-onset impairment in gas exchange between the lungs and the blood, lead to hypoxemia with or without hypercapnia. Usual management of this condition relies on oxygen supplementation throughout different respiratory support modalities (i.e., low flow oxygen devices, high-flow nasal cannulas, mechanical ventilation, ECMO, etc.) aiming to restore gas exchange and to support respiratory effort. In most cases, initial management of acute hypoxemic respiratory failure might be provided through low-flow oxygen systems, but more severe cases will require more advanced life-supporting strategies.

Respiratory compromise by SARS-CoV-2 infection widely varies between subjects. Thus, respiratory system elastance, intrapulmonary shunt, pulmonary perfusion/ventilation inequalities and lung weight can range between almost normal up to very high values. Consequently, modalities to provide initial support in acute severe hypoxemic respiratory failure in SARS-CoV-2 infection should not be limited to immediate invasive mechanical ventilation support as such respiratory support modalities should be adapted to individual requirements.

Unfortunately, similar values of initial PaO2/FiO2 ratios (especially when PaO2/FiO2 ratio is < 200) are not clearly related with more or less severe lung affectation, high or low respiratory system elastance patterns, high or low adaptive hypoxic vasoconstriction, and far beyond clinical signs, there are no widely available methods able to rapidly decide which patients would be more benefit from a relative "conservative" management or on the contrary, which patient would benefit from immediate invasive respiratory support.

Use of high-flow nasal cannulas (HFNC) in acute hypoxemic respiratory failure from different etiologies has rapidly increased during the last years. Certainly, randomized controlled trials suggest that HFNC might prevent intubation and the need for invasive mechanical ventilation in patients with moderate and severe hypoxemia. Nevertheless, impact of HFNC on mortality rates and other important clinical outcomes in this condition remains controversial.

Initial observational reports of patients with severe SARS-CoV-2 infection subjected to invasive mechanical ventilation showed a consistent and very high mortality. Indeed, some experts claimed for using such non-invasive respiratory support devices in patients with moderate or even high pulmonary shunt values arguing about possible harm induced by mechanical ventilation especially in patients with a relative normal respiratory system elastance. Nevertheless, others recommended against HFNC use because safety concerns for health care workers, which clearly limited its use at the initial phases of the pandemic. Thus, the impact and safety of using HFNC at very early stages of acute hypoxemic respiratory failure induced by severe SARS-CoV-2 infection remain to be elucidated. This is how the HiFlo-COVID trial propose to assess the impact HFNC vs. conventional oxygen therapy on the need for intubation / invasive mechanical ventilation support and the clinical status (at days-14 and -28) as assessed by a modified 7-point ordinal scale in patients with moderate / severe hypoxemic respiratory failure secondary to SARS-CoV-2 infection.

Study Design

Study Type:

Interventional

Actual Enrollment :

199 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Phase II, multicenter, randomized, open-label, controlled study of the use of high flow nasal cannula respiratory support vs. conventional oxygen therapy in patients with moderate/severe hypoxemic respiratory failure secondary to SARS-CoV-2 infection.Phase II, multicenter, randomized, open-label, controlled study of the use of high flow nasal cannula respiratory support vs. conventional oxygen therapy in patients with moderate/severe hypoxemic respiratory failure secondary to SARS-CoV-2 infection.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Trial of High-Flow Nasal Cannula vs. Conventional Oxygen Therapy in Patients With SARS-CoV-2-Related Acute Respiratory Failure: the HiFlo-COVID Trial.

Actual Study Start Date :

Aug 11, 2020

Actual Primary Completion Date :

Jan 13, 2021

Actual Study Completion Date :

Feb 10, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Conventional oxygen therapy (COT) group Oxygen therapy will be delivered by conventional nasal cannula / prongs, venturi mask, or mask with reservoir, with flows between 3 and 15 liters / minute, to ensure SpO2 ≥ 92%.	Procedure: Conventional oxygen therapy Oxygen therapy by conventional nasal cannula / prongs, venturi mask, or mask with reservoir
Experimental: High-flow nasal cannula (HFNC) group Breathing support with High-Flow oxygen therapy, flow will be initiated between 50 and 60 liters / minute. FiO2 60% to 100% with the objective of reaching SpO2 ≥ 92%. Adequate wetting of the system should be ensured according to the recommendations of the HFNC device manufacturer. FiO2 may be decreased gradually according to the patient's individual condition, trying to maintain SpO2 ≥ 92%.	Procedure: High flow nasal cannula Breathing support with High-flow nasal cannula

Arm

Intervention/Treatment

Active Comparator: Conventional oxygen therapy (COT) group

Oxygen therapy will be delivered by conventional nasal cannula / prongs, venturi mask, or mask with reservoir, with flows between 3 and 15 liters / minute, to ensure SpO2 ≥ 92%.

Procedure: Conventional oxygen therapy

Oxygen therapy by conventional nasal cannula / prongs, venturi mask, or mask with reservoir

Experimental: High-flow nasal cannula (HFNC) group

Breathing support with High-Flow oxygen therapy, flow will be initiated between 50 and 60 liters / minute. FiO2 60% to 100% with the objective of reaching SpO2 ≥ 92%. Adequate wetting of the system should be ensured according to the recommendations of the HFNC device manufacturer. FiO2 may be decreased gradually according to the patient's individual condition, trying to maintain SpO2 ≥ 92%.

Procedure: High flow nasal cannula

Breathing support with High-flow nasal cannula

Outcome Measures

Primary Outcome Measures

Intubation rate [28 days]
Need for intubation / support with invasive mechanical ventilation.
Clinical recovery [28 days]
Time to improvement of clinical status according to the 7-point ordinal scale. Modified 7-point ordinal scale: An ordinal scale of 7 points where 1= Ambulatory/no limitation of activities and 7= Death. Low scores denote a better outcome and high scores denote a worse outcome. Time to reduction in scale score will be measured (daily scale scoring).

Secondary Outcome Measures

Proportion of patients with requirement of early mechanical ventilation. [7 and 14 days]
Whether or not each patient required mechanical ventilation during the first 7 and 14 days after randomization will be assessed. Proportion of patients with early mechanical ventilation will be calculated for each group.
Mechanical ventilation-free days [28 days]
Days off from mechanical ventilation
Renal replacement therapy-free days [28 days]
Days off from renal replacement therapy
Length of ICU stay [28 days]
Duration of stay in ICU
Length of hospital stay [28 days]
Duration of hospital stay
All-cause day-28 mortality [28 days]
Hospital mortality
Proportion of serious adverse events [28 days]
Proportion of patients with serious adverse events during hospital stay
Proportion of bacterial - fungal infections [28 days]
Proportion of bacterial - fungal infections during hospital stay

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adults > 18 years.
Emergency or ICU admission with suspected/confirmed SARS-CoV-2 infection.
Moderate/severe acute respiratory failure:
PaO2/FiO2 < 200.
Use of accessory muscles.
Breathing rate > 25 x minute.
Have a progression < 6 hours since meeting the definition of moderate/severe acute respiratory failure secondary to suspected/confirmed SARS-CoV-2 infection.

Exclusion Criteria:

Adults < 18 years.
Indication for immediate orotracheal intubation.
Pregnant woman / positive pregnancy test at the time of potential inclusion in the study.
Chronic liver disease / liver cirrhosis Child-Pugh C.
Confirmation of active bacterial or fungal infection.
Uncontrolled HIV/AIDS disease (defined by presence of viral load > 200 copies/mL).
Previous history of COPD Gold C - D.
History of COPD requiring hospitalization - hospitalization / ICU in the last year.
Known history of congestive heart failure NYHA III - IV.
Left ventricular ejection fraction < 45% previously known.
Highly suspected or confirmed cardiogenic pulmonary edema.
Hypercapnic respiratory failure (PaCO2 > 55 mmHg).
Central/peripheral demyelinating disorders due to medical history or high suspicion of these at the time of study eligibility.
Patient who in the investigator's judgment suggests a progression to death is imminent and inevitable within the next 24 hours.
Any serious medical condition or clinical laboratory test abnormality that, in the investigator's judgment, prevents safe patient participation and completion of the study.
Participation in another clinical trial (except one related to SARS-CoV-2 - CRITERIA TO BE DISCUSSED BETWEEN GROUP OF RESEARCHES).