Covid19HiFlo-COVIDNCT04609462
High-Flow Nasal Cannula in Severe COVID-19 With Acute Hypoxemic Respiratory Failure.
A study testing Conventional oxygen therapy and High flow nasal cannula in people with Covid19 and Acute Hypoxemic Respiratory Failure, run by Fundacion Clinica Valle del Lili at 1 site in Colombia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19, Acute Hypoxemic Respiratory Failure
- What is being tested?
- Conventional oxygen therapy and High flow nasal cannula
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 199 participants
- Where
- 1 siteColombia
- Study dates
- 11 Aug 2020to 10 Feb 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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).
Trial locations and contacts
1 site in 1 country.
Colombia1 site
Fundacion Valle del Lili
Cali, Valle del Cauca Department, 76032
About this study
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.
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.
Read the 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.
- Conditions
- Covid19, Acute Hypoxemic Respiratory Failure
- Being tested
- Conventional oxygen therapy, High flow nasal cannula
- Keywords
- Acute Hypoxemic Respiratory Failure, SARS-CoV-2 infection, High flow nasal cannula, Conventional oxygen therapy, Oxygen therapy
- Medical subject headings
- COVID-19, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conventional oxygen therapyProcedure or surgery
Oxygen therapy by conventional nasal cannula / prongs, venturi mask, or mask with reservoir
High flow nasal cannulaProcedure or surgery
Breathing support with High-flow nasal cannula
| Study group | Role | What they receive |
|---|---|---|
| Conventional oxygen therapy (COT) group | Active comparator | 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%. Receives: Procedure: Conventional oxygen therapy |
| High-flow nasal cannula (HFNC) group | Experimental | 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%. Receives: Procedure: High flow nasal cannula |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intubation rate
Need for intubation / support with invasive mechanical ventilation.
Measured: 28 days
Clinical recovery
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).
Measured: 28 days
Secondary outcomes (8)
Proportion of patients with requirement of early mechanical ventilation.
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.
Measured: 7 and 14 days
Mechanical ventilation-free days
Days off from mechanical ventilation
Measured: 28 days
Renal replacement therapy-free days
Days off from renal replacement therapy
Measured: 28 days
Length of ICU stay
Duration of stay in ICU
Measured: 28 days
Length of hospital stay
Duration of hospital stay
Measured: 28 days
All-cause day-28 mortality
Hospital mortality
Measured: 28 days
Proportion of serious adverse events
Proportion of patients with serious adverse events during hospital stay
Measured: 28 days
Proportion of bacterial - fungal infections
Proportion of bacterial - fungal infections during hospital stay
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2020
- Study start11 Aug 2020
- Primary completion13 Jan 2021
- Study completion10 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- None (open label)
- Enrolment
- 199 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundacion Clinica Valle del Lili
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gustavo A. Ospina Tascón, MDPhD, Principal investigator, Fundacion Clinica Valle del Lili
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04609462
- Sponsor's protocol ID
- 001635
- Acronym
- HiFlo-COVID
- Status last verified
- Mar 2021
- First submitted
- 24 Sep 2020
- Last updated
- 1 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Ospina-Tascon GA, Calderon-Tapia LE, Garcia AF, Zarama V, Gomez-Alvarez F, Alvarez-Saa T, Pardo-Otalvaro S, Bautista-Rincon DF, Vargas MP, Aldana-Diaz JL, Marulanda A, Gutierrez A, Varon J, Gomez M, Ochoa ME, Escobar E, Umana M, Diez J, Tobon GJ, Albornoz LL, Celemin Florez CA, Ruiz GO, Caceres EL, Reyes LF, Damiani LP, Cavalcanti AB; HiFLo-Covid Investigators. Effect of High-Flow Oxygen Therapy vs Conventional Oxygen Therapy on Invasive Mechanical Ventilation and Clinical Recovery in Patients With Severe COVID-19: A Randomized Clinical Trial. JAMA. 2021 Dec 7;326(21):2161-2171. doi: 10.1001/jama.2021.20714.
PubMed 34874419
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT04609462
- Acronym / sponsor ID
- HiFlo-COVID / 001635
- Conditions
- Covid19, Acute Hypoxemic Respiratory Failure
- Keywords
- Acute Hypoxemic Respiratory Failure, SARS-CoV-2 infection, High flow nasal cannula, Conventional oxygen therapy, Oxygen therapy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 199 participants (actual)
- Lead sponsor
- Fundacion Clinica Valle del LiliUniversity, hospital or other
- Study start
- 11 Aug 2020 (actual)
- Primary completion
- 13 Jan 2021 (actual)
- Study completion
- 10 Feb 2021 (actual)
- First posted
- 30 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Conventional oxygen therapy (COT) group | Active comparator | Procedure: Conventional oxygen therapyOxygen 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%. |
| High-flow nasal cannula (HFNC) group | Experimental | Procedure: High flow nasal cannulaBreathing 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%. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Conventional oxygen therapyOxygen therapy by conventional nasal cannula / prongs, venturi mask, or mask with reservoir | Procedure or surgery | Conventional oxygen therapy (COT) group |
| High flow nasal cannulaBreathing support with High-flow nasal cannula | Procedure or surgery | High-flow nasal cannula (HFNC) group |
Primary outcome
Intubation rate
Time frame: 28 days
Need for intubation / support with invasive mechanical ventilation.
Clinical recovery
Time frame: 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).
8 secondary outcomes
Proportion of patients with requirement of early mechanical ventilation.
Time frame: 7 and 14 days
Mechanical ventilation-free days
Time frame: 28 days
Renal replacement therapy-free days
Time frame: 28 days
Length of ICU stay
Time frame: 28 days
Length of hospital stay
Time frame: 28 days
All-cause day-28 mortality
Time frame: 28 days
Proportion of serious adverse events
Time frame: 28 days
Proportion of bacterial - fungal infections
Time frame: 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2021.
- Derived from this study: PubMed 34874419Ospina-Tascon GA, Calderon-Tapia LE, Garcia AF, Zarama V, Gomez-Alvarez F, Alvarez-Saa T, Pardo-Otalvaro S, Bautista-Rincon DF, Vargas MP, Aldana-Diaz JL, Marulanda A, Gutierrez A, Varon J, Gomez M, Ochoa ME, Escobar E, Umana M, Diez J, Tobon GJ, Albornoz LL, Celemin Florez CA, Ruiz GO, Caceres EL, Reyes LF, Damiani LP, Cavalcanti AB; HiFLo-Covid Investigators. Effect of High-Flow Oxygen Therapy vs Conventional Oxygen Therapy on Invasive Mechanical Ventilation and Clinical Recovery in Patients With Severe COVID-19: A Randomized Clinical Trial. JAMA. 2021 Dec 7;326(21):2161-2171. doi: 10.1001/jama.2021.20714.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gustavo A. Ospina Tascón, MDPhD principal investigator
Fundacion Clinica Valle del Lili
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Conventional oxygen therapy and High flow nasal cannula in people with Covid19 and Acute Hypoxemic Respiratory Failure, run by Fundacion Clinica Valle del Lili at 1 site in Colombia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Colombia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intubation rate (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04609462, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2021.