COVID-HIGH: HFNT vs. COT in COVID-19
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: High Flow Nasal Therapy High flow nasal therapy |
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%.
|
| Active Comparator: Conventional Oxygen Therapy Conventional Oxygen therapy |
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%.
|
Outcome Measures
Primary Outcome Measures
- Proportion of patients needing escalation of treatment during hospital stay [28 days]
Proportion of patients needing escalation of treatment (i.e. noninvasive ventilation - including CPAP - or intubation).
Secondary Outcome Measures
- Proportion of patients needing intubation during hospital stay [28 days]
- Proportion of patients who receive CPAP during hospital stay [28 days]
Proportion of patients who receive continuous positive airway pressure during hospital stay
- Proportion of patients who receive NIV during hospital stay [28 days]
Proportion of patients undergone noninvasive ventilation (e.g. BiLevel, PSV)
- Proportion of patients admitted to intensive care unit during hospital stay [28 days]
- Proportion of patients who terminate the study protocols for improvement [28 days]
- Length of stay in hospital [28 days]
- Time to escalation of treatment to CPAP/NIV during hospital stay [28 days]
- Time to escalation of treatment to intubation/invasive ventilation during hospital stay [28 days]
- Length of stay in ICU [28 day]
- Days free from CPAP/NIV during hospital stay [28 days]
- Ventilator-free days during hospital stay [28 days]
- Oxygen-free days during hospital stay [28 days]
- 28-day mortality [28 days from hospital admission]
- 60-day mortality [60 days from hospital admission]
- Hospital mortality [28 days]
- Treatment interruption due to intolerance during study treatment [28 days]
- Dyspnea score (BORG scale) during hospital stay [28 days]
[0= no dyspnea to 10= severe dyspnea] - daily collection
- National Early Warning Score 2 (NEWS2) during hospital stay [28 days]
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.
- ROX index during hospital stay [28 days]
SpO2/FiO2/Respiratory rate - daily collection
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age ≥ 18 years old
-
Tested positive for SARS-CoV-2 using real-time reverse transcriptase PCR (RT-PCR) nasopharyngeal swabs
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Clinical signs of acute respiratory infection and radiological evidence of pneumonia
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Hospital admission in any ward or Emergency Department within 48 h
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SpO2 ≤ 92% or PaO2/FiO2 < 300 in room air and need for oxygen therapy according to clinical judgment, at the screening.
Exclusion Criteria:
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PaO2/FiO2 ≤ 200
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Respiratory rate ≥ 28 breaths/min and or severe dyspnea and or use of accessory muscles
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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)
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Patients already on CPAP/NIV or HFNT at study screening
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Septic shock
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Evidence of multiorgan failure
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Glasgow Coma Scale < 13
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Inability to comprehend the study content and give informed consent
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PaCO2 > 45 mmHg, (if blood gas available) or history of chronic hypercapnia
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Patient already on long-term oxygen therapy (LTOT) or home NIV/CPAP (even if only overnight)
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Neuromuscular disease
-
Limitation of care based on patients' or physicians' decision
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Emergency Medicine, Faculty of Medicine, University of Thessaly | Larisa | Greece | ||
| 2 | Department of Anesthesiology, University of Thessaly, School of Health Sciences, Faculty of Medicine | Larissa | Greece | ||
| 3 | UO di Pronto Soccorso e Medicina d'Urgenza Humanitas Research Hospital | Rozzano | Milano | Italy | |
| 4 | U.O. di Medicina interna AULSS 7 Pedemontana | Bassano del Grappa | VI | Italy | |
| 5 | Pulmonology and Respiratory Intensive Care Unit, S. Donato Hospital, Arezzo, Italy | Arezzo | Italy | ||
| 6 | Institute of Respiratory Disease, Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari | Bari | Italy | ||
| 7 | Ospedale di Carpi | Carpi | Italy | ||
| 8 | Respiratory Medicine Unit, "Policlinico-Vittorio Emanuele San Marco" University Hospital, Catania, Italy | Catania | Italy | ||
| 9 | UO di Medicina d'Urgenza AOU Policlinico Vittorio Emanuele San Marco di Catania | Catania | Italy | ||
| 10 | Respiratory Section, Department of Translational Medicine, University of Ferrara. AOU Ferrara Arcispedale S. Anna. U.O. Pneumologia | Ferrara | Italy | ||
| 11 | Department of Medical and Surgical Sciences, University of Foggia. Institute of Respiratory Diseases, University Hospital 'Policlinico Riuniti' | Foggia | Italy | ||
| 12 | UO di Pneumologia ASST Fatebenefratelli Sacco | Milano | Italy | ||
| 13 | AO DEI COLLI - PO Monaldi UO di Pneumologia e Fisiopatologia Respiratoria | Napoli | Italy | ||
| 14 | AOU San Luigi Gonzaga | Orbassano | Italy | ||
| 15 | Emergency Department, "S. Maria della Misericordia" Hospital, Perugia, Italy. | Perugia | Italy | ||
| 16 | U.O. di Pneumologia Azienda USL di Pescara | Pescara | Italy | ||
| 17 | UO di Pronto Soccorso e Medicina d'Urgenza AUSL Romagna PO Rimini Ospedale "Inferni" | Rimini | Italy | ||
| 18 | U.O. di PneumoCovid Azienda Ospedaliera San Giovanni di Roma | Roma | Italy | ||
| 19 | UO di Pneumologia Ospedale S. Bartolomeo | Sarzana | Italy | ||
| 20 | Department of Pneumology, A.O.U. Città della Salute e della Scienza of Turin, Italy. | Turin | Italy | ||
| 21 | U.O. di Pneumologia ASST Settelaghi Ospedale Circolo Fondazione Macchi | Varese | Italy | ||
| 22 | U.O. Medicina Respiratoria del Policlinico G.B. Rossi | Verona | Italy | ||
| 23 | U.O. di Pneumotisiologia Ospedale di Vittorio Veneto Azienda ULSS 2 Marca Trevigiana | Vittorio Veneto | Italy | ||
| 24 | Department of Pneumonology, Faculty of Medical Sciences in Katowice, Medical University of Silesia | Katowice | Poland | ||
| 25 | Hospital Prof. Doutor Fernando Fonseca, Pneumologia | Amadora | Portugal | ||
| 26 | Hospital Parc Taulí de Sabadell, Pneumologia | Sabadell | Spain | ||
| 27 | Dokuz Eylül University | İzmir | Turkey |
Sponsors and Collaborators
- Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo
- Azienda Ospedaliera, Universitaria Policlinico Vittorio Emanuele
Investigators
- Principal Investigator: Andrea Cortegiani, MD, University of Palermo. Azienda Ospedaliera Policlinico Paolo Giaccone
- Principal Investigator: Claudia Crimi, MD, Respiratory Medicine Unit, "Policlinico-Vittorio Emanuele San Marco" University Hospital
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 1th Dec 2020