Comparison of High Flow Nasal Cannula (HFNC), Face-mask Non-Invasive Ventilation (NIV) & Helmet NIV in COVID-19 ARDS Patients (NIV COVID19)

December 22, 2021 updated by: Abdulhakeem Al-Hashim, Sultan Qaboos University

Objective: To determine whether NIV delivered through helmet interface reduces intubation rate among patients with COVID-19 ARDS compared to face-mask NIV and HFNC.

Design, setting & participants: Two-center randomized clinical trial of 360 patients with mild to moderate ARDS and confirmed COVID-19 requiring non-invasive ventilation between August 2020 to January 2021. The patients with respiratory rate (RR) more than 30/min or oxygen saturation (SpO2) less than 90% or PaO2/FiO2 ratio less than 300 despite standard oxygen therapy by face mask (<15 L/min) who present to Royal hospital or Sultan Qaboos University Hospital (SQUH) emergency department, medical wards or intensive care unit (ICU).

Intervention: Patients will be randomly assigned (block randomization) to either face-mask NIV, HFNC or Helmet NIV. The helmet is a transparent hood that covers the entire head of the patient and has a rubber collar neck seal.

Main outcome and measures: The primary outcome is the rate of endotracheal intubation at 28-days. Secondary outcomes include hospital mortality at 28 and 90 days, NIV free days, invasive ventilator free days and hospital length of stay.

Expected results: We assume the failure rate of Helmet NIV to be 30%, failure rate of HFNC to be 40% and failure rate of face-mask NIV to be 50%. A sample size of 360 patients (120/group) will achieve a power of 0.90 at a significance level of 0.05. To account for 10% dropout rate, the total sample required is 396 subjects(132/group).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Inclusion criteria:

  • > 18 years of age
  • confirmed COVID-19
  • Within 48 hours of presentation in the emergency department, high dependency area or intensive care unit (ICU)
  • ARDS according to Berlin definition (P/F < 300) or O2 saturation < 90% or RR > 30/min) in room air
  • Standard oxygen therapy at flow rate < 15L/min x 60 minutes

Exclusion criteria:

  • More than 48 hours of admission to the emergency room, high dependency or intensive care unit
  • On non-invasive ventilation or HFNC for more than 4 hours before enrollement
  • Impending cardiopulmonary arrest
  • Need for immediate endotracheal intubation
  • Hemodynamic instability or life-threatening arrhythmias
  • GCS < 8
  • Active intracranial pathology or high ICP
  • Inability to cooperate or protect the airway
  • Pregnancy
  • Tracheostomy
  • DNR or refusing intubation
  • Known type 2 respiratory failure
  • On chronic home oxygen therapy

Enrolment:

Multi-centre randomized trial of confirmed COVID-19 cases presenting to the emergency department, the ward, high dependency or intensive care unit (ICU) with ARDS requiring non-invasive mechanical ventilation. It is an open label randomized clinical trial. We will perform permuted block randomization of 9 and perform concealment.

Consent:

A written consent must be taken from the patient or the decision maker prior to enrollment.

Each of the three arms have pre-specified treatment protocol in the form of algorithm.

For the helmet NIV group, for type 1 respiratory failure (hypoxemia & normal pCO2), CPAP will be started at 10 cmH2O & FiO2 0.6. Re-assessment will be done every 15-30 minutes and CPAP and FiO2 will be increased accordinly (CPAP to 15 & FiO2 of 1.0 maximum) If patients develops hypercapnia, the mode will be changed to BiPAP: IPAP 12-25 cmH2O (max 20) EPAP 8-15 cmH2O.

In the face-mask NIV group, CPAP will be started at 5 cmH2O & FiO2 0.6. Re-assess will be performed every15-30 minutes. Thereafter CPAP & FiO2 will be adjusted accordingly (maximum CPAP 12 & FiO2: 1.0) If the patient develops high pCO2 :BiPAP: IPAP 8-20 cmH2O (max 20) EPAP 4-12 cmH2O.

In the high flow nasal cannula group, HFNC will be started at at 20-30 L/min Adjust FiO2 to keep SpO2 > 92%. Thereafter, it will be titrated to flow to max 60 L/min & FiO2 100%

For all the three groups, these are the following targets:

Target:

SPO2 ≥ 92 % RR ≤ 30/min ROX index > 2.85 at 2 hours and > 3.85 at 12 hours (HFNC group)

If the above targets are not achieved, the ICU team will assess them for possible endotracheal intubation. In case the patient doesn't tolerate any of the two NIV interfaces, they will be allowed to cross over to the other with intention to treat analysis. For the high flow oxygen group, a trial of non-invasive ventilation will be allowed at the physician discretion before endotracheal intubation with intention to treat analysis.

Statistical Analysis:

We tested the null hypothesis that there is no difference between the Helmet-NIV, HFNC and face-mask-NIV intubation rate and the alternative hypothesis that Helmet NIV and HFNC is superior to face-mask-NIV. We assumed the failure rate of Helmet NIV to be 30% and the failure rate of HFNC to be 40% and failure rate of face-mask NIV is 50%. The group subject counts are allocated 1:1:1. The effect size is 0.12. A sample of 360 subjects, (120/group) achieves a power of 0.90 at a significance level of 0.05. To account for 10% dropout rate, the total sample required is 396 subjects(132/group).

Baseline characteristics will be reported by mean and standard deviation for the continuous variables and numbers and proportions for categorical variables. Intention to treat analysis to analysis will be used for the results for the primary efficacy point of reduction in the rate of the intubation between the three groups. Fisher's exact test will be used between-group differences in the rate of intubation. The face-mask-NIV is considered as a control group as it is the standard treatment and will calculate t the relative risk and absolute risk difference for the primary end points. The log-rank test will compare the time from enrollment to ET intubation for the three groups using Kaplan-Meier curves plot. Similar analysis will be performed for the 28-day mortality for as the secondary end points. All P values reported for on primary and secondary end points are based on two-sided tests of 0.05. The SAS statistical software is used to analyze the data.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
161

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Oman
      • Muscat, Oman, 123
        • Sultan Qaboos University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • > 18 years of age
  • confirmed COVID-19
  • Within 48 hours of presentation in the emergency department, high dependency area or intensive care unit (ICU)
  • ARDS according to Berlin definition (P/F < 300) or O2 saturation < 90% or RR > 30/min) in room air
  • Standard oxygen therapy at flow rate < 15L/min x 60 minutes

Exclusion Criteria:

  • More than 48 hours of admission to the emergency department, high dependency or intensive care unit
  • More than 4 hours on NIV or HFNC before enrolment
  • Impending cardiopulmonary arrest
  • Need for immediate endotracheal intubation
  • Hemodynamic instability or life-threatening arrhythmias
  • GCS < 8
  • Active intracranial pathology or high ICP
  • Inability to cooperate or protect the airway
  • Pregnancy
  • Tracheostomy
  • DNR or refusing intubation
  • Known type 2 respiratory failure
  • On chronic home oxygen therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: control
Face-mask NIV is the standard of care
Device: Face-mask NIV
NIV interface
Active Comparator: intervention 1
High flow nasal cannula
Device: High flow nasal cannula (HFNC)
High flow nasal cannula as a form of non-invasive oxygen delivery
Active Comparator: Intervention 2
Helmet NIV
Device: Helmet NIV
NIV interface

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Rate of endotracheal intubation
Time Frame: within the study period with an average of one month.
The patient will be randomly assigned to one of the treatment arms. Then the patient will be followed up for one month for the primary outcome which is endotracheal intubation.
within the study period with an average of one month.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Hospital mortality
Time Frame: 90 days from the hospital mortality.
Number of patients who survived compared to who died in each intervention
90 days from the hospital mortality.
Hospital length of stay
Time Frame: Throughout the study completion. An average of 90 days.
total number of days patients remain in the hospital as inpatient in each intervention
Throughout the study completion. An average of 90 days.
Ventilator free days
Time Frame: Throughout the study completion. An average of 90 days.
number of days patients remain off intervention (invasive or non-invasive)
Throughout the study completion. An average of 90 days.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sultan Qaboos University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 2, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 9, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 11, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 9, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 16, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 20, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 12, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 22, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SQU-EC/206/2020

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Publish in a journal

IPD Sharing Time Frame

after July 2021

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

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