HFNT vs. COT in COVID-19

NCT ID: NCT04655638

Last Updated: 2021-10-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

364 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-02-10

Study Completion Date

2021-10-25

Brief Summary

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The aim of this unblinded parallel-group randomized multicenter clinical trial is to compare the clinical effectiveness of high flow nasal therapy (HFNT) with conventional oxygen therapy (COT) in patients with confirmed COVID-19 related acute hypoxemic respiratory failure.

Detailed Description

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The interventions will be delivered in any hospital ward caring for COVID-19 patients.

The interventions under investigation will be high flow nasal therapy in comparison with conventional oxygen therapy.

HFNT will be delivered by any device (standalone machine or ventilators able to deliver it). The initial flow rate will be set at 40 L/min and potentially increased up to 60 L/min, according to patient tolerance. Large-bore nasal prongs will be selected according to the size of patients' nostrils (i.e. 2/3 of the diameter of the patient's nostril). A surgical mask will be placed on top of the HFNT interface. The temperature will be set at 37°C or 34 °C according to the patient's comfort. The FiO2 will be adjusted to maintain SpO2 between 92-96%. A feeding tube or a nasogastric tube will not represent a contraindication for the use of HFNT provided the patency of the used nostril.

Conventional Oxygen therapy will be delivered by any device or combination of devices used for delivering oxygen such as nasal cannula, Venturi Mask or Mask with or without a reservoir bag as per usual local practice. Oxygen flow will be titrated to achieve SpO2 between 92-96%.

Co-interventions: Patients potentially eligible for the study will be evaluated by the attending physicians and receive medical therapy based on the attending physician's decision and local protocols. Awake proning is allowed. Local protocols, including drugs and awake proning, will be discussed with the enrolling centers at the initiation visit, and adherence to WHO guidelines will be recommended. Written informed consent from all the patients will be collected.

Termination criteria \& protocol violation: Criteria for weaning off COT or HFNT was at clinical discretion of the managing physician based on the improvement in oxygenation with ability to maintain SpO2 of 96% or greater with less than 0.30 of FiO2 or P/F \> 300. The switch from COT to HFNT should be considered a protocol violation and should be based on clinical decision of the treating physician.

Criteria to be considered for escalation of treatment: 1) SpO2 ≤ 92% despite COT or HFNT or P/F ≤ 180 with FiO2 ≥ 50%, and 2) at least one of the following: respiratory rate ≥ 28 breaths/min, severe dyspnea, signs of increased work of breathing (e.g. use of accessory muscles). If the patient meets these criteria, escalation of treatment CPAP, NIV or IMV will be considered.

The choice of the type of escalating treatment will be a clinical decision of the treating physician.

Conditions

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Covid19 Acute Respiratory Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Unblinded parallel-group randomized multicenter clinical trial
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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High Flow Nasal Therapy

High flow nasal therapy

Group Type EXPERIMENTAL

High Flow Nasal Therapy

Intervention Type DEVICE

High flow nasal therapy will be delivered by any device (standalone machine or ventilators able to deliver it). The initial flow rate will be set at 40 L/min and potentially increased up to 60 L/min, according to patient tolerance. Large-bore nasal prongs will be selected according to the size of patients' nostrils (i.e. 2/3 of the diameter of the patient's nostril). A surgical mask will be placed on top of the HFNT interface. The temperature will be set at 37°C or 34 °C according to the patient's comfort. The FiO2 will be adjusted to maintain SpO2 between 92-96%.

Conventional Oxygen Therapy

Conventional Oxygen therapy

Group Type ACTIVE_COMPARATOR

Conventional Oxygen Therapy

Intervention Type DEVICE

Conventional Oxygen therapy will be delivered by any device or combination of devices used for delivering oxygen such as nasal cannula, Venturi Mask or Mask with or without a reservoir bag as per usual local practice. Oxygen flow will be titrated to achieve SpO2 between 92-96%.

Interventions

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High Flow Nasal Therapy

High flow nasal therapy will be delivered by any device (standalone machine or ventilators able to deliver it). The initial flow rate will be set at 40 L/min and potentially increased up to 60 L/min, according to patient tolerance. Large-bore nasal prongs will be selected according to the size of patients' nostrils (i.e. 2/3 of the diameter of the patient's nostril). A surgical mask will be placed on top of the HFNT interface. The temperature will be set at 37°C or 34 °C according to the patient's comfort. The FiO2 will be adjusted to maintain SpO2 between 92-96%.

Intervention Type DEVICE

Conventional Oxygen Therapy

Conventional Oxygen therapy will be delivered by any device or combination of devices used for delivering oxygen such as nasal cannula, Venturi Mask or Mask with or without a reservoir bag as per usual local practice. Oxygen flow will be titrated to achieve SpO2 between 92-96%.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* Age ≥ 18 years old
* Tested positive for SARS-CoV-2 using real-time reverse transcriptase PCR (RT-PCR) nasopharyngeal swabs
* Clinical signs of acute respiratory infection and radiological evidence of pneumonia
* Hospital admission in any ward or Emergency Department within 48 h
* SpO2 ≤ 92% or PaO2/FiO2 \< 300 in room air and need for oxygen therapy according to clinical judgment, at the screening.

Exclusion Criteria

* PaO2/FiO2 ≤ 200
* Respiratory rate ≥ 28 breaths/min and or severe dyspnea and or use of accessory muscles
* Need for immediate intubation or noninvasive ventilation (including CPAP) according to clinical judgment (e.g. clinical diagnosis of cardiogenic pulmonary edema, respiratory acidosis pH ≤ 7.3)
* Patients already on CPAP/NIV or HFNT at study screening
* Septic shock
* Evidence of multiorgan failure
* Glasgow Coma Scale \< 13
* Inability to comprehend the study content and give informed consent
* PaCO2 \> 45 mmHg, (if blood gas available) or history of chronic hypercapnia
* Patient already on long-term oxygen therapy (LTOT) or home NIV/CPAP (even if only overnight)
* Neuromuscular disease
* Limitation of care based on patients' or physicians' decision
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Azienda Ospedaliera, Universitaria Policlinico Vittorio Emanuele

OTHER

Sponsor Role collaborator

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo

OTHER

Sponsor Role lead

Responsible Party

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Andrea Cortegiani, MD

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Andrea Cortegiani, MD

Role: PRINCIPAL_INVESTIGATOR

University of Palermo. Azienda Ospedaliera Policlinico Paolo Giaccone

Claudia Crimi, MD

Role: PRINCIPAL_INVESTIGATOR

Respiratory Medicine Unit, "Policlinico-Vittorio Emanuele San Marco" University Hospital

Locations

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Department of Anesthesiology, University of Thessaly, School of Health Sciences, Faculty of Medicine

Larissa, , Greece

Site Status

Department of Emergency Medicine, Faculty of Medicine, University of Thessaly

Larissa, , Greece

Site Status

UO di Pronto Soccorso e Medicina d'Urgenza Humanitas Research Hospital

Rozzano, Milano, Italy

Site Status

U.O. di Medicina interna AULSS 7 Pedemontana

Bassano del Grappa, VI, Italy

Site Status

Pulmonology and Respiratory Intensive Care Unit, S. Donato Hospital, Arezzo, Italy

Arezzo, , Italy

Site Status

Institute of Respiratory Disease, Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari

Bari, , Italy

Site Status

Ospedale di Carpi

Carpi, , Italy

Site Status

Respiratory Medicine Unit, "Policlinico-Vittorio Emanuele San Marco" University Hospital, Catania, Italy

Catania, , Italy

Site Status

UO di Medicina d'Urgenza AOU Policlinico Vittorio Emanuele San Marco di Catania

Catania, , Italy

Site Status

Respiratory Section, Department of Translational Medicine, University of Ferrara. AOU Ferrara Arcispedale S. Anna. U.O. Pneumologia

Ferrara, , Italy

Site Status

Department of Medical and Surgical Sciences, University of Foggia. Institute of Respiratory Diseases, University Hospital 'Policlinico Riuniti'

Foggia, , Italy

Site Status

UO di Pneumologia ASST Fatebenefratelli Sacco

Milan, , Italy

Site Status

AO DEI COLLI - PO Monaldi UO di Pneumologia e Fisiopatologia Respiratoria

Napoli, , Italy

Site Status

AOU San Luigi Gonzaga

Orbassano, , Italy

Site Status

Emergency Department, "S. Maria della Misericordia" Hospital, Perugia, Italy.

Perugia, , Italy

Site Status

U.O. di Pneumologia Azienda USL di Pescara

Pescara, , Italy

Site Status

UO di Pronto Soccorso e Medicina d'Urgenza AUSL Romagna PO Rimini Ospedale "Inferni"

Rimini, , Italy

Site Status

U.O. di PneumoCovid Azienda Ospedaliera San Giovanni di Roma

Roma, , Italy

Site Status

UO di Pneumologia Ospedale S. Bartolomeo

Sarzana, , Italy

Site Status

Department of Pneumology, A.O.U. Città della Salute e della Scienza of Turin, Italy.

Turin, , Italy

Site Status

U.O. di Pneumologia ASST Settelaghi Ospedale Circolo Fondazione Macchi

Varese, , Italy

Site Status

U.O. Medicina Respiratoria del Policlinico G.B. Rossi

Verona, , Italy

Site Status

U.O. di Pneumotisiologia Ospedale di Vittorio Veneto Azienda ULSS 2 Marca Trevigiana

Vittorio Veneto, , Italy

Site Status

Department of Pneumonology, Faculty of Medical Sciences in Katowice, Medical University of Silesia

Katowice, , Poland

Site Status

Hospital Prof. Doutor Fernando Fonseca, Pneumologia

Amadora, , Portugal

Site Status

Hospital Parc Taulí de Sabadell, Pneumologia

Sabadell, , Spain

Site Status

Dokuz Eylül University

Izmir, , Turkey (Türkiye)

Site Status

Countries

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Greece Italy Poland Portugal Spain Turkey (Türkiye)

References

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Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. No abstract available.

Reference Type BACKGROUND
PMID: 32091533 (View on PubMed)

Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.

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Rochwerg B, Einav S, Chaudhuri D, Mancebo J, Mauri T, Helviz Y, Goligher EC, Jaber S, Ricard JD, Rittayamai N, Roca O, Antonelli M, Maggiore SM, Demoule A, Hodgson CL, Mercat A, Wilcox ME, Granton D, Wang D, Azoulay E, Ouanes-Besbes L, Cinnella G, Rauseo M, Carvalho C, Dessap-Mekontso A, Fraser J, Frat JP, Gomersall C, Grasselli G, Hernandez G, Jog S, Pesenti A, Riviello ED, Slutsky AS, Stapleton RD, Talmor D, Thille AW, Brochard L, Burns KEA. The role for high flow nasal cannula as a respiratory support strategy in adults: a clinical practice guideline. Intensive Care Med. 2020 Dec;46(12):2226-2237. doi: 10.1007/s00134-020-06312-y. Epub 2020 Nov 17.

Reference Type BACKGROUND
PMID: 33201321 (View on PubMed)

Crimi C, Noto A, Cortegiani A, Impellizzeri P, Elliott M, Ambrosino N, Gregoretti C. Noninvasive respiratory support in acute hypoxemic respiratory failure associated with COVID-19 and other viral infections. Minerva Anestesiol. 2020 Nov;86(11):1190-1204. doi: 10.23736/S0375-9393.20.14785-0. Epub 2020 Aug 5.

Reference Type BACKGROUND
PMID: 32756535 (View on PubMed)

Alhazzani W, Moller MH, Arabi YM, Loeb M, Gong MN, Fan E, Oczkowski S, Levy MM, Derde L, Dzierba A, Du B, Aboodi M, Wunsch H, Cecconi M, Koh Y, Chertow DS, Maitland K, Alshamsi F, Belley-Cote E, Greco M, Laundy M, Morgan JS, Kesecioglu J, McGeer A, Mermel L, Mammen MJ, Alexander PE, Arrington A, Centofanti JE, Citerio G, Baw B, Memish ZA, Hammond N, Hayden FG, Evans L, Rhodes A. Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19). Crit Care Med. 2020 Jun;48(6):e440-e469. doi: 10.1097/CCM.0000000000004363.

Reference Type BACKGROUND
PMID: 32224769 (View on PubMed)

Braunlich J, Mauersberger F, Wirtz H. Effectiveness of nasal highflow in hypercapnic COPD patients is flow and leakage dependent. BMC Pulm Med. 2018 Jan 24;18(1):14. doi: 10.1186/s12890-018-0576-x.

Reference Type BACKGROUND
PMID: 29368599 (View on PubMed)

Crimi C, Noto A, Madotto F, Ippolito M, Nolasco S, Campisi R, De Vuono S, Fiorentino G, Pantazopoulos I, Chalkias A, Libra A, Mattei A, Scala R, Clini EM, Ergan B, Lujan M, Winck JC, Giarratano A, Carlucci A, Gregoretti C, Groff P, Cortegiani A; COVID-HIGH Investigators. High-flow nasal oxygen versus conventional oxygen therapy in patients with COVID-19 pneumonia and mild hypoxaemia: a randomised controlled trial. Thorax. 2023 Apr;78(4):354-361. doi: 10.1136/thoraxjnl-2022-218806. Epub 2022 May 17.

Reference Type DERIVED
PMID: 35580898 (View on PubMed)

Other Identifiers

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1th Dec 2020

Identifier Type: -

Identifier Source: org_study_id