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.
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.
Procedure: Conventional oxygen therapy
Oxygen therapy by conventional nasal cannula / prongs, venturi mask, or mask with reservoir
Procedure: High flow nasal cannula
Breathing support with High-flow nasal cannula
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).
Fundacion Valle del Lili
Cali, Valle Del Cauca, Colombia
Gustavo A. Ospina Tascón, MDPhD, Principal Investigator
Fundacion Clinica Valle del Lili