HFNT vs. COT in COVID-19

Covid19 Clinical Trial

— COVID-HIGH  

Official title:

High-Flow Nasal Therapy Versus Conventional Oxygen Therapy in Patients With COVID-19: A Randomized Controlled Trial (The COVID-HIGH Trial)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04655638
• Other study ID #: 1th Dec 2020
• Status: Completed
• Phase: N/A
• Start date: February 10, 2021
• Est. completion date: October 25, 2021

Study information

• Verified date: October 2021
• Source: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 364
• Est. completion date: October 25, 2021
• Est. primary completion date: September 22, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Respiratory Failure
• COVID-19
• Covid19
• Respiratory Insufficiency

Intervention

Device:
• 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%.
• 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%.

Locations

Country	Name	City	State
Greece	Department of Emergency Medicine, Faculty of Medicine, University of Thessaly	Larisa
Greece	Department of Anesthesiology, University of Thessaly, School of Health Sciences, Faculty of Medicine	Larissa
Italy	Pulmonology and Respiratory Intensive Care Unit, S. Donato Hospital, Arezzo, Italy	Arezzo
Italy	Institute of Respiratory Disease, Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari	Bari
Italy	U.O. di Medicina interna AULSS 7 Pedemontana	Bassano del Grappa	VI
Italy	Ospedale di Carpi	Carpi
Italy	Respiratory Medicine Unit, "Policlinico-Vittorio Emanuele San Marco" University Hospital, Catania, Italy	Catania
Italy	UO di Medicina d'Urgenza AOU Policlinico Vittorio Emanuele San Marco di Catania	Catania
Italy	Respiratory Section, Department of Translational Medicine, University of Ferrara. AOU Ferrara Arcispedale S. Anna. U.O. Pneumologia	Ferrara
Italy	Department of Medical and Surgical Sciences, University of Foggia. Institute of Respiratory Diseases, University Hospital 'Policlinico Riuniti'	Foggia
Italy	UO di Pneumologia ASST Fatebenefratelli Sacco	Milano
Italy	AO DEI COLLI - PO Monaldi UO di Pneumologia e Fisiopatologia Respiratoria	Napoli
Italy	AOU San Luigi Gonzaga	Orbassano
Italy	Emergency Department, "S. Maria della Misericordia" Hospital, Perugia, Italy.	Perugia
Italy	U.O. di Pneumologia Azienda USL di Pescara	Pescara
Italy	UO di Pronto Soccorso e Medicina d'Urgenza AUSL Romagna PO Rimini Ospedale "Inferni"	Rimini
Italy	U.O. di PneumoCovid Azienda Ospedaliera San Giovanni di Roma	Roma
Italy	UO di Pronto Soccorso e Medicina d'Urgenza Humanitas Research Hospital	Rozzano	Milano
Italy	UO di Pneumologia Ospedale S. Bartolomeo	Sarzana
Italy	Department of Pneumology, A.O.U. Città della Salute e della Scienza of Turin, Italy.	Turin
Italy	U.O. di Pneumologia ASST Settelaghi Ospedale Circolo Fondazione Macchi	Varese
Italy	U.O. Medicina Respiratoria del Policlinico G.B. Rossi	Verona
Italy	U.O. di Pneumotisiologia Ospedale di Vittorio Veneto Azienda ULSS 2 Marca Trevigiana	Vittorio Veneto
Poland	Department of Pneumonology, Faculty of Medical Sciences in Katowice, Medical University of Silesia	Katowice
Portugal	Hospital Prof. Doutor Fernando Fonseca, Pneumologia	Amadora
Spain	Hospital Parc Taulí de Sabadell, Pneumologia	Sabadell
Turkey	Dokuz Eylül University	Izmir

Sponsors (2)

Lead Sponsor	Collaborator
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo	Azienda Ospedaliera, Universitaria Policlinico Vittorio Emanuele

Countries where clinical trial is conducted

Greece,  Italy,  Poland,  Portugal,  Spain,  Turkey, 

References & Publications (6)

Alhazzani W, Møller 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. — View Citation

Bräunlich 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients needing escalation of treatment during hospital stay	Proportion of patients needing escalation of treatment (i.e. noninvasive ventilation - including CPAP - or intubation).	28 days
Secondary	Proportion of patients needing intubation during hospital stay		28 days
Secondary	Proportion of patients who receive CPAP during hospital stay	Proportion of patients who receive continuous positive airway pressure during hospital stay	28 days
Secondary	Proportion of patients who receive NIV during hospital stay	Proportion of patients undergone noninvasive ventilation (e.g. BiLevel, PSV)	28 days
Secondary	Proportion of patients admitted to intensive care unit during hospital stay		28 days
Secondary	Proportion of patients who terminate the study protocols for improvement		28 days
Secondary	Length of stay in hospital		28 days
Secondary	Time to escalation of treatment to CPAP/NIV during hospital stay		28 days
Secondary	Time to escalation of treatment to intubation/invasive ventilation during hospital stay		28 days
Secondary	Length of stay in ICU		28 day
Secondary	Days free from CPAP/NIV during hospital stay		28 days
Secondary	Ventilator-free days during hospital stay		28 days
Secondary	Oxygen-free days during hospital stay		28 days
Secondary	28-day mortality		28 days from hospital admission
Secondary	60-day mortality		60 days from hospital admission
Secondary	Hospital mortality		28 days
Secondary	Treatment interruption due to intolerance during study treatment		28 days
Secondary	Dyspnea score (BORG scale) during hospital stay	[0= no dyspnea to 10= severe dyspnea] - daily collection	28 days
Secondary	National Early Warning Score 2 (NEWS2) during hospital stay	Daily collection of Six simple physiological parameters that form the basis of the scoring system: respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness or new confusion, temperature. A score is allocated to each parameter, with the magnitude of the score reflecting how extremely the parameter varies from the norm. The score is then aggregated and uplifted by 2 points for people requiring supplemental oxygen to maintain their recommended oxygen saturation. Range of values: 0 (best) - 23 (worst) points.	28 days
Secondary	ROX index during hospital stay	SpO2/FiO2/Respiratory rate - daily collection	28 days

External Links

•   NIH. COVID 19 Treatment Guidelines.
•   Prevention CCfDCa.