Early PP With HFNC Versus HFNC in COVID-19 Induced Moderate to Severe ARDS

• Sponsor: Rush University Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT04325906
• Collaborator: (none)
• Enrollment: 224
• Location: 1
• Arms: 2
• Actual Duration (Months): 10.7
• Patients Per Site Per Month: 21

Study Details

Study Description

Brief Summary

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and had subsequently spread worldwide. Twenty-nine percent of COVID-19 patients may develop ARDS. Based on the potential beneficial mechanisms of HFNC and PP, whether early use of prone positioning combined with HFNC can avoid the need for intubation in COVID-19 induced moderate to severe ARDS patients needs to be further investigated.

Condition or Disease	Intervention/Treatment	Phase
Prone Positioning; High Flow Nasal Cannula; Acute Respiratory Distress Syndrome; Corona Virus Infection	Device: high flow nasal cannula (HFNC); Procedure: Prone positioning (PP)	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 224 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Early Prone Positioning Combined With High-Flow Nasal Cannula Versus High-Flow Nasal Cannula in COVID-19 Induced Moderate to Severe ARDS
• Actual Study Start Date: Apr 2, 2020
• Actual Primary Completion Date: Jan 26, 2021
• Actual Study Completion Date: Feb 21, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: high flow nasal cannula only Receive high flow nasal cannula only	Device: high flow nasal cannula (HFNC); HFNC will be initiated at 50 L/min (AIRVO2 or Optiflow, Fisher &Paykel Health care Limited., Auckland, New Zealand) with temperature set at 37 oC. Nasal cannula size will be determined by the patient's nostril size (≤ 50%). FIO2 will be adjusted to maintain SpO2 at 92% to 95%. Flow and temperature will be adjusted based on patient's comfort and clinical response.
Experimental: HFNC plus prone positioning Receive high flow nasal cannula plus prone positioning	Device: high flow nasal cannula (HFNC); HFNC will be initiated at 50 L/min (AIRVO2 or Optiflow, Fisher &Paykel Health care Limited., Auckland, New Zealand) with temperature set at 37 oC. Nasal cannula size will be determined by the patient's nostril size (≤ 50%). FIO2 will be adjusted to maintain SpO2 at 92% to 95%. Flow and temperature will be adjusted based on patient's comfort and clinical response.; Procedure: Prone positioning (PP); PP will be performed before or 1 hour after meal. Before PP, all the I.V. lines and nasal cannula will be checked by clinicians. PP will be performed by patient under the supervision of clinicians. Assistance will be offered if needed. If tolerated, PP will be maintained for at least 30 minutes, until the patients feel tired to keep that position. PP will be performed twice a day for the first 3 days after the patient's enrollment. FIO2 will be adjusted to maintain SpO2 at 92-95%.

Outcome Measures

Primary Outcome Measures

1. Treatment Failure (Intubation or Death) [28 days]

   the treatment failure rate of HFNC/HFNC+PP support within 28 days of study enrollment

2. Number of Participants With Intubation [28 days]

   intubation rate of HFNC/HFNC+PP support within 28 days of study enrollment

3. Mortality [28 days]

   mortality of HFNC/HFNC+PP support within 28 days of study enrollment

Secondary Outcome Measures

1. Number of Participants With Adverse Events [28 days of study enrollment]

   adverse events include skin breakdown, vomiting, arterial or central line dislodgement, and cardiac arrest

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• COVID-19 induced adult ARDS patients admitted to the medical ICU

• PaO2/FiO2 is less than 200mmHg or FIO2 ≥ 0.4 is required to maintain SpO2 at 88-93% on HFNC treatment

Exclusion Criteria:

1. If the patients have a consistent SpO2<80% when on evaluation with a FiO2 of 0.6, or signs of respiratory fatigue (RR > 40/min, PaCO2> 50mmHg / pH<7.30, and obvious accessory respiratory muscle use);

2. Immediate need for intubation (PaO2/FiO2< 50mmHg or SpO2/FiO2 <90, unable to protect airway or mental status change);

3. unstable hemodynamic status(SBP<90mmHg, MBP below 65 mmHg or requirement for vasopressor);

4. unable to collaborate with HFNC/PP with agitation or refuse HFNC/PP.

5. chest trauma or any contraindication for PP

6. pneumothorax

7. age < 18 years

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rush University Medical Center	Chicago	Illinois	United States	60612

Sponsors and Collaborators

• Rush University Medical Center

Investigators

• Principal Investigator: Jie Li, PhD, Rush University Medical Center

Study Documents (Full-Text)

• Study Protocol and Informed Consent Form: Informed Consent Form - Apr 1, 2020
• Study Protocol and Statistical Analysis Plan: Study Protocol and Statistical Analysis Plan - Sep 15, 2020

More Information

Publications

• Ding L, Wang L, Ma W, He H. Efficacy and safety of early prone positioning combined with HFNC or NIV in moderate to severe ARDS: a multi-center prospective cohort study. Crit Care. 2020 Jan 30;24(1):28. doi: 10.1186/s13054-020-2738-5.
• Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, Prat G, Boulain T, Morawiec E, Cottereau A, Devaquet J, Nseir S, Razazi K, Mira JP, Argaud L, Chakarian JC, Ricard JD, Wittebole X, Chevalier S, Herbland A, Fartoukh M, Constantin JM, Tonnelier JM, Pierrot M, Mathonnet A, Béduneau G, Delétage-Métreau C, Richard JC, Brochard L, Robert R; FLORALI Study Group; REVA Network. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015 Jun 4;372(23):2185-96. doi: 10.1056/NEJMoa1503326. Epub 2015 May 17.
• Guérin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, Mercier E, Badet M, Mercat A, Baudin O, Clavel M, Chatellier D, Jaber S, Rosselli S, Mancebo J, Sirodot M, Hilbert G, Bengler C, Richecoeur J, Gainnier M, Bayle F, Bourdin G, Leray V, Girard R, Baboi L, Ayzac L; PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013 Jun 6;368(23):2159-68. doi: 10.1056/NEJMoa1214103. Epub 2013 May 20.
• Li J, Pavlov I, Laffey JG, Roca O, Mirza S, Perez Y, McNicholas B, Cosgrave D, Vines D, Tavernier E, Ehrmann S. Meta-trial of awake prone positioning with nasal high flow therapy: Invitation to join a pandemic collaborative research effort. J Crit Care. 2020 Dec;60:140-142. doi: 10.1016/j.jcrc.2020.07.020. Epub 2020 Jul 24.
• Munshi L, Del Sorbo L, Adhikari NKJ, Hodgson CL, Wunsch H, Meade MO, Uleryk E, Mancebo J, Pesenti A, Ranieri VM, Fan E. Prone Position for Acute Respiratory Distress Syndrome. A Systematic Review and Meta-Analysis. Ann Am Thorac Soc. 2017 Oct;14(Supplement_4):S280-S288. doi: 10.1513/AnnalsATS.201704-343OT. Review.
• Pavlov I, He H, McNicholas B, Perez Y, Tavernier E, Trump MW, Jackson JA, Zhang W, Rubin DS, Spiegel T, Hung A, Estrada MÁI, Roca O, Vines DL, Cosgrave D, Mirza S, Laffey JG, Rice TW, Ehrmann S, Li J. Awake Prone Positioning in Non-Intubated Patients With Acute Hypoxemic Respiratory Failure Due to COVID-19. Respir Care. 2021 Jul 7. pii: respcare.09191. doi: 10.4187/respcare.09191. [Epub ahead of print] Review.
• Respiratory care committee of Chinese Thoracic Society. [Expert consensus on preventing nosocomial transmission during respiratory care for critically ill patients infected by 2019 novel coronavirus pneumonia]. Zhonghua Jie He He Hu Xi Za Zhi. 2020 Feb 20;17(0):E020. doi: 10.3760/cma.j.issn.1001-0939.2020.0020. [Epub ahead of print] Chinese.
• Scholten EL, Beitler JR, Prisk GK, Malhotra A. Treatment of ARDS With Prone Positioning. Chest. 2017 Jan;151(1):215-224. doi: 10.1016/j.chest.2016.06.032. Epub 2016 Jul 8. Review.
• Tavernier E, McNicholas B, Pavlov I, Roca O, Perez Y, Laffey J, Mirza S, Cosgrave D, Vines D, Frat JP, Ehrmann S, Li J. Awake prone positioning of hypoxaemic patients with COVID-19: protocol for a randomised controlled open-label superiority meta-trial. BMJ Open. 2020 Nov 11;10(11):e041520. doi: 10.1136/bmjopen-2020-041520.

• Responsible Party: Rush University Medical Center
• ClinicalTrials.gov Identifier: NCT04325906
• Other Study ID Numbers: COVID-19-HFNC+PP
• First Posted: Mar 30, 2020
• Last Update Posted: Mar 2, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Additional relevant MeSH terms: Coronavirus Infections; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury

Study Results

Participant Flow

Arm/Group Title	High Flow Nasal Cannula Only	HFNC Plus Prone Positioning
Arm/Group Description	Receive high flow nasal cannula only high flow nasal cannula (HFNC): HFNC will be initiated at 50 L/min (AIRVO2 or Optiflow, Fisher &Paykel Health care Limited., Auckland, New Zealand) with temperature set at 37 oC. Nasal cannula size will be determined by the patient's nostril size (≤ 50%). FIO2 will be adjusted to maintain SpO2 at 92% to 95%. Flow and temperature will be adjusted based on patient's comfort and clinical response.	Receive high flow nasal cannula plus prone positioning high flow nasal cannula (HFNC): HFNC will be initiated at 50 L/min (AIRVO2 or Optiflow, Fisher &Paykel Health care Limited., Auckland, New Zealand) with temperature set at 37 oC. Nasal cannula size will be determined by the patient's nostril size (≤ 50%). FIO2 will be adjusted to maintain SpO2 at 92% to 95%. Flow and temperature will be adjusted based on patient's comfort and clinical response. Prone positioning (PP): PP will be performed before or 1 hour after meal. Before PP, all the I.V. lines and nasal cannula will be checked by clinicians. PP will be performed by patient under the supervision of clinicians. Assistance will be offered if needed. If tolerated, PP will be maintained for at least 30 minutes, until the patients feel tired to keep that position. PP will be performed twice a day for the first 3 days after the patient's enrollment. FIO2 will be adjusted to maintain SpO2 at 92-95%.
Period Title: Overall Study
STARTED	112	112
COMPLETED	110	112
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	High Flow Nasal Cannula Only	HFNC Plus Prone Positioning	Total
Arm/Group Description	Receive high flow nasal cannula only high flow nasal cannula (HFNC): HFNC will be initiated at 50 L/min (AIRVO2 or Optiflow, Fisher &Paykel Health care Limited., Auckland, New Zealand) with temperature set at 37 oC. Nasal cannula size will be determined by the patient's nostril size (≤ 50%). FIO2 will be adjusted to maintain SpO2 at 92% to 95%. Flow and temperature will be adjusted based on patient's comfort and clinical response.	Receive high flow nasal cannula plus prone positioning high flow nasal cannula (HFNC): HFNC will be initiated at 50 L/min (AIRVO2 or Optiflow, Fisher &Paykel Health care Limited., Auckland, New Zealand) with temperature set at 37 oC. Nasal cannula size will be determined by the patient's nostril size (≤ 50%). FIO2 will be adjusted to maintain SpO2 at 92% to 95%. Flow and temperature will be adjusted based on patient's comfort and clinical response. Prone positioning (PP): PP will be performed before or 1 hour after meal. Before PP, all the I.V. lines and nasal cannula will be checked by clinicians. PP will be performed by patient under the supervision of clinicians. Assistance will be offered if needed. If tolerated, PP will be maintained for at least 30 minutes, until the patients feel tired to keep that position. PP will be performed twice a day for the first 3 days after the patient's enrollment. FIO2 will be adjusted to maintain SpO2 at 92-95%.	Total of all reporting groups
Overall Participants	110	112	222
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.5 (13.3)	62.2 (12.5)	62.3 (12.9)
Sex: Female, Male (Count of Participants)
Female	42 38.2%	40 35.7%	82 36.9%
Male	68 61.8%	72 64.3%	140 63.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	57 51.8%	65 58%	122 55%
Not Hispanic or Latino	53 48.2%	47 42%	100 45%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Treatment Failure (Intubation or Death)
Description	the treatment failure rate of HFNC/HFNC+PP support within 28 days of study enrollment
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High Flow Nasal Cannula Only	HFNC Plus Prone Positioning
Arm/Group Description	Receive high flow nasal cannula only high flow nasal cannula (HFNC): HFNC will be initiated at 50 L/min (AIRVO2 or Optiflow, Fisher &Paykel Health care Limited., Auckland, New Zealand) with temperature set at 37 oC. Nasal cannula size will be determined by the patient's nostril size (≤ 50%). FIO2 will be adjusted to maintain SpO2 at 92% to 95%. Flow and temperature will be adjusted based on patient's comfort and clinical response.	Receive high flow nasal cannula plus prone positioning high flow nasal cannula (HFNC): HFNC will be initiated at 50 L/min (AIRVO2 or Optiflow, Fisher &Paykel Health care Limited., Auckland, New Zealand) with temperature set at 37 oC. Nasal cannula size will be determined by the patient's nostril size (≤ 50%). FIO2 will be adjusted to maintain SpO2 at 92% to 95%. Flow and temperature will be adjusted based on patient's comfort and clinical response. Prone positioning (PP): PP will be performed before or 1 hour after meal. Before PP, all the I.V. lines and nasal cannula will be checked by clinicians. PP will be performed by patient under the supervision of clinicians. Assistance will be offered if needed. If tolerated, PP will be maintained for at least 30 minutes, until the patients feel tired to keep that position. PP will be performed twice a day for the first 3 days after the patient's enrollment. FIO2 will be adjusted to maintain SpO2 at 92-95%.
Measure Participants	110	112
Count of Participants [Participants]	45 40.9%	45 40.2%

2. Primary Outcome

Title	Number of Participants With Intubation
Description	intubation rate of HFNC/HFNC+PP support within 28 days of study enrollment
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High Flow Nasal Cannula Only	HFNC Plus Prone Positioning
Arm/Group Description	Receive high flow nasal cannula only high flow nasal cannula (HFNC): HFNC will be initiated at 50 L/min (AIRVO2 or Optiflow, Fisher &Paykel Health care Limited., Auckland, New Zealand) with temperature set at 37 oC. Nasal cannula size will be determined by the patient's nostril size (≤ 50%). FIO2 will be adjusted to maintain SpO2 at 92% to 95%. Flow and temperature will be adjusted based on patient's comfort and clinical response.	Receive high flow nasal cannula plus prone positioning high flow nasal cannula (HFNC): HFNC will be initiated at 50 L/min (AIRVO2 or Optiflow, Fisher &Paykel Health care Limited., Auckland, New Zealand) with temperature set at 37 oC. Nasal cannula size will be determined by the patient's nostril size (≤ 50%). FIO2 will be adjusted to maintain SpO2 at 92% to 95%. Flow and temperature will be adjusted based on patient's comfort and clinical response. Prone positioning (PP): PP will be performed before or 1 hour after meal. Before PP, all the I.V. lines and nasal cannula will be checked by clinicians. PP will be performed by patient under the supervision of clinicians. Assistance will be offered if needed. If tolerated, PP will be maintained for at least 30 minutes, until the patients feel tired to keep that position. PP will be performed twice a day for the first 3 days after the patient's enrollment. FIO2 will be adjusted to maintain SpO2 at 92-95%.
Measure Participants	110	112
Count of Participants [Participants]	39 35.5%	38 33.9%

3. Primary Outcome

Title	Mortality
Description	mortality of HFNC/HFNC+PP support within 28 days of study enrollment
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High Flow Nasal Cannula Only	HFNC Plus Prone Positioning
Arm/Group Description	Receive high flow nasal cannula only high flow nasal cannula (HFNC): HFNC will be initiated at 50 L/min (AIRVO2 or Optiflow, Fisher &Paykel Health care Limited., Auckland, New Zealand) with temperature set at 37 oC. Nasal cannula size will be determined by the patient's nostril size (≤ 50%). FIO2 will be adjusted to maintain SpO2 at 92% to 95%. Flow and temperature will be adjusted based on patient's comfort and clinical response.	Receive high flow nasal cannula plus prone positioning high flow nasal cannula (HFNC): HFNC will be initiated at 50 L/min (AIRVO2 or Optiflow, Fisher &Paykel Health care Limited., Auckland, New Zealand) with temperature set at 37 oC. Nasal cannula size will be determined by the patient's nostril size (≤ 50%). FIO2 will be adjusted to maintain SpO2 at 92% to 95%. Flow and temperature will be adjusted based on patient's comfort and clinical response. Prone positioning (PP): PP will be performed before or 1 hour after meal. Before PP, all the I.V. lines and nasal cannula will be checked by clinicians. PP will be performed by patient under the supervision of clinicians. Assistance will be offered if needed. If tolerated, PP will be maintained for at least 30 minutes, until the patients feel tired to keep that position. PP will be performed twice a day for the first 3 days after the patient's enrollment. FIO2 will be adjusted to maintain SpO2 at 92-95%.
Measure Participants	110	112
Count of Participants [Participants]	30 27.3%	21 18.8%

4. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	adverse events include skin breakdown, vomiting, arterial or central line dislodgement, and cardiac arrest
Time Frame	28 days of study enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High Flow Nasal Cannula Only	HFNC Plus Prone Positioning
Arm/Group Description	Receive high flow nasal cannula only high flow nasal cannula (HFNC): HFNC will be initiated at 50 L/min (AIRVO2 or Optiflow, Fisher &Paykel Health care Limited., Auckland, New Zealand) with temperature set at 37 oC. Nasal cannula size will be determined by the patient's nostril size (≤ 50%). FIO2 will be adjusted to maintain SpO2 at 92% to 95%. Flow and temperature will be adjusted based on patient's comfort and clinical response.	Receive high flow nasal cannula plus prone positioning high flow nasal cannula (HFNC): HFNC will be initiated at 50 L/min (AIRVO2 or Optiflow, Fisher &Paykel Health care Limited., Auckland, New Zealand) with temperature set at 37 oC. Nasal cannula size will be determined by the patient's nostril size (≤ 50%). FIO2 will be adjusted to maintain SpO2 at 92% to 95%. Flow and temperature will be adjusted based on patient's comfort and clinical response. Prone positioning (PP): PP will be performed before or 1 hour after meal. Before PP, all the I.V. lines and nasal cannula will be checked by clinicians. PP will be performed by patient under the supervision of clinicians. Assistance will be offered if needed. If tolerated, PP will be maintained for at least 30 minutes, until the patients feel tired to keep that position. PP will be performed twice a day for the first 3 days after the patient's enrollment. FIO2 will be adjusted to maintain SpO2 at 92-95%.
Measure Participants	110	112
Count of Participants [Participants]	0 0%	2 1.8%

Adverse Events

Time Frame	Within 28 days of study enrollment
Arm/Group Title	High Flow Nasal Cannula Only		HFNC Plus Prone Positioning
Arm/Group Description	Receive high flow nasal cannula only high flow nasal cannula (HFNC): HFNC will be initiated at 50 L/min (AIRVO2 or Optiflow, Fisher &Paykel Health care Limited., Auckland, New Zealand) with temperature set at 37 oC. Nasal cannula size will be determined by the patient's nostril size (≤ 50%). FIO2 will be adjusted to maintain SpO2 at 92% to 95%. Flow and temperature will be adjusted based on patient's comfort and clinical response.		Receive high flow nasal cannula plus prone positioning high flow nasal cannula (HFNC): HFNC will be initiated at 50 L/min (AIRVO2 or Optiflow, Fisher &Paykel Health care Limited., Auckland, New Zealand) with temperature set at 37 oC. Nasal cannula size will be determined by the patient's nostril size (≤ 50%). FIO2 will be adjusted to maintain SpO2 at 92% to 95%. Flow and temperature will be adjusted based on patient's comfort and clinical response. Prone positioning (PP): PP will be performed before or 1 hour after meal. Before PP, all the I.V. lines and nasal cannula will be checked by clinicians. PP will be performed by patient under the supervision of clinicians. Assistance will be offered if needed. If tolerated, PP will be maintained for at least 30 minutes, until the patients feel tired to keep that position. PP will be performed twice a day for the first 3 days after the patient's enrollment. FIO2 will be adjusted to maintain SpO2 at 92-95%.
All Cause Mortality
	High Flow Nasal Cannula Only		HFNC Plus Prone Positioning
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/110 (27.3%)		21/112 (18.8%)
Serious Adverse Events
	High Flow Nasal Cannula Only		HFNC Plus Prone Positioning
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/110 (0%)		0/112 (0%)
Other (Not Including Serious) Adverse Events
	High Flow Nasal Cannula Only		HFNC Plus Prone Positioning
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/110 (0%)		2/112 (1.8%)
Surgical and medical procedures
Central or arterial line dislodgement	0/110 (0%)	0	2/112 (1.8%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The study funder (Rice foundation) had no role in study design, data analysis, the preparation or approval of the manuscript, or the decision to submit the manuscript for publication