Clinical trial NCT04655638: HFNT vs. COT in COVID-19
Official title: High-Flow Nasal Therapy Versus Conventional Oxygen Therapy in Patients With COVID-19: A Randomized Controlled Trial (The COVID-HIGH Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Covid19
Acute Respiratory Failure
Keywords: COVID-19
HFNT
Respiratory failure
COT
Oxygen
Pneumonia
Lead sponsor: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo
Sponsor class: OTHER
Collaborators: name: Azienda Ospedaliera, Universitaria Policlinico Vittorio Emanuele
First posted: 2020-12-07
Enrollment: 364
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Unblinded parallel-group randomized multicenter clinical trial
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients needing escalation of treatment during hospital stay
timeFrame: 28 days
Secondary outcomes:
measure: Proportion of patients needing intubation during hospital stay
timeFrame: 28 days
measure: Proportion of patients who receive CPAP during hospital stay
timeFrame: 28 days
measure: Proportion of patients who receive NIV during hospital stay
timeFrame: 28 days
measure: Proportion of patients admitted to intensive care unit during hospital stay
timeFrame: 28 days
measure: Proportion of patients who terminate the study protocols for improvement
timeFrame: 28 days
measure: Length of stay in hospital
timeFrame: 28 days
measure: Time to escalation of treatment to CPAP/NIV during hospital stay
timeFrame: 28 days
measure: Time to escalation of treatment to intubation/invasive ventilation during hospital stay
timeFrame: 28 days
measure: Length of stay in ICU
timeFrame: 28 day
measure: Days free from CPAP/NIV during hospital stay
timeFrame: 28 days
measure: Ventilator-free days during hospital stay
timeFrame: 28 days
measure: Oxygen-free days during hospital stay
timeFrame: 28 days
measure: 28-day mortality
timeFrame: 28 days from hospital admission
measure: 60-day mortality
timeFrame: 60 days from hospital admission
measure: Hospital mortality
timeFrame: 28 days
measure: Treatment interruption due to intolerance during study treatment
timeFrame: 28 days
measure: Dyspnea score (BORG scale) during hospital stay
timeFrame: 28 days
measure: National Early Warning Score 2 (NEWS2) during hospital stay
timeFrame: 28 days
measure: ROX index during hospital stay
timeFrame: 28 days
Other outcomes:
Locations:
city: Larisa
country: Greece
facility: Department of Emergency Medicine, Faculty of Medicine, University of Thessaly
city: Larissa
country: Greece
facility: Department of Anesthesiology, University of Thessaly, School of Health Sciences, Faculty of Medicine
city: Rozzano
country: Italy
facility: UO di Pronto Soccorso e Medicina d'Urgenza Humanitas Research Hospital
state: Milano
city: Bassano del Grappa
country: Italy
facility: U.O. di Medicina interna AULSS 7 Pedemontana
state: VI
city: Arezzo
country: Italy
facility: Pulmonology and Respiratory Intensive Care Unit, S. Donato Hospital, Arezzo, Italy
city: Bari
country: Italy
facility: Institute of Respiratory Disease, Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari
city: Carpi
country: Italy
facility: Ospedale di Carpi
city: Catania
country: Italy
facility: Respiratory Medicine Unit, "Policlinico-Vittorio Emanuele San Marco" University Hospital, Catania, Italy
city: Catania
country: Italy
facility: UO di Medicina d'Urgenza AOU Policlinico Vittorio Emanuele San Marco di Catania
city: Ferrara
country: Italy
facility: Respiratory Section, Department of Translational Medicine, University of Ferrara. AOU Ferrara Arcispedale S. Anna. U.O. Pneumologia
city: Foggia
country: Italy
facility: Department of Medical and Surgical Sciences, University of Foggia. Institute of Respiratory Diseases, University Hospital 'Policlinico Riuniti'
city: Milano
country: Italy
facility: UO di Pneumologia ASST Fatebenefratelli Sacco
city: Napoli
country: Italy
facility: AO DEI COLLI - PO Monaldi UO di Pneumologia e Fisiopatologia Respiratoria
city: Orbassano
country: Italy
facility: AOU San Luigi Gonzaga
city: Perugia
country: Italy
facility: Emergency Department, "S. Maria della Misericordia" Hospital, Perugia, Italy.
city: Pescara
country: Italy
facility: U.O. di Pneumologia Azienda USL di Pescara
city: Rimini
country: Italy
facility: UO di Pronto Soccorso e Medicina d'Urgenza AUSL Romagna PO Rimini Ospedale "Inferni"
city: Roma
country: Italy
facility: U.O. di PneumoCovid Azienda Ospedaliera San Giovanni di Roma
city: Sarzana
country: Italy
facility: UO di Pneumologia Ospedale S. Bartolomeo
city: Turin
country: Italy
facility: Department of Pneumology, A.O.U. Città della Salute e della Scienza of Turin, Italy.
city: Varese
country: Italy
facility: U.O. di Pneumologia ASST Settelaghi Ospedale Circolo Fondazione Macchi
city: Verona
country: Italy
facility: U.O. Medicina Respiratoria del Policlinico G.B. Rossi
city: Vittorio Veneto
country: Italy
facility: U.O. di Pneumotisiologia Ospedale di Vittorio Veneto Azienda ULSS 2 Marca Trevigiana
city: Katowice
country: Poland
facility: Department of Pneumonology, Faculty of Medical Sciences in Katowice, Medical University of Silesia
city: Amadora
country: Portugal
facility: Hospital Prof. Doutor Fernando Fonseca, Pneumologia
city: Sabadell
country: Spain
facility: Hospital Parc Taulí de Sabadell, Pneumologia
city: İzmir
country: Turkey
facility: Dokuz Eylül University
Study officials:
affiliation: University of Palermo. Azienda Ospedaliera Policlinico Paolo Giaccone
name: Andrea Cortegiani, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Respiratory Medicine Unit, "Policlinico-Vittorio Emanuele San Marco" University Hospital
name: Claudia Crimi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.