Respiratory Supports and COVID-19 Mortality

May 10, 2021 updated by: Yale University

Respiratory Supports and COVID-19 Mortality: a One-year Cohort Study Across a Health Care System

Critically ill COVID-19 patients have a relatively high mortality rate (~30%). Most critically ill COVID-19 patients require respiratory supports. The respiratory supports used in this patient population included conventional oxygen therapy (COT) via nasal cannula or face mask, non-invasive ventilation (NIV), and invasive mechanical ventilation (IMV). NIV has three different methods, including high-flow nasal cannula (HFNC), bilevel positive airway pressure (BiPAP), and continuous positive airway pressure (CPAP). There are outstanding questions that remain to be answered. One is which NIV is more effective; the other is if the use of IMV leads to increased mortality. Another relevant question is if ventilator settings (such as tidal volume, drive pressure, and positive end-expiratory pressure) are associated with different mechanical ventilated patients' outcomes. To answer these questions, a retrospective cohort study based on all patients who had been treated in the ICUs in Yale New Haven Health System throughout the first pandemic year was designed.

Study Overview

Status

Status

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

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

Statistical methods

Continuous data are presented as mean and standard deviation (SD) if it follows a normal distribution assessed using histograms and Q-Q plots; otherwise, as median and interquartile range (IQR). Categorical data are presented as numbers and percentages. Missing data will not be imputed. Patients from a specific analysis were excluded if the data for the related variable are missing.

The first objective is to investigate the relative effectiveness of different NIVs, including high-flow nasal cannula (HFNC), bilevel positive airway pressure (BiPAP), and continuous positive airway pressure (CPAP). Patients will be divided into three groups per the type of NIV they first received. Patients who received invasive mechanical ventilation (IMV) before NIV will be excluded. Patients who received two or three different types of NIV will also be excluded in this analysis. Patients who received IMV after the use of NIV are eligible.

The secondary objective is to investigate the impact of IMV on mortality via comparison with patients who received NIV only. The role of lung protective ventilation in patients who received IMV will also be investigated. The characteristics of the ventilator settings that are associated with an improved outcome will be explored.

The primary outcome is in-hospital mortality and patients will be followed until hospital discharge. Patients are considered alive if they were discharged alive from the hospital or are still hospitalized at the closure of data extraction. For the first objective, the rate of respiratory support escalation from NIV to IMV will also be analyzed (as a secondary outcome measure in this analysis).

Patients will be balanced using propensity score matching. The propensity score model will include demographic characteristics, comorbidities, the pandemic phase, severity of acute illness (24 hours before the targeted respiratory support), laboratory results (24 hours before the targeted respiratory support), and vital signs (24 hours before the targeted respiratory support). The balance between matched pairs will be assessed using a standardized 10% difference and calculated using the method described by Yang and Dalton. A stratified Cox proportional-hazards model will be used to analyze the matched pairs. Additionally, survival will be estimated using the product-limit Kaplan-Meier estimator, and the log-rank statistic will be used to compare survival curves.

The backup statistical analysis plan is as follows. The univariate Cox proportional-hazard models to screen for potential factors associated with lower mortality will be performed. A multivariable Cox proportional-hazards model to estimate independent associations between respiratory supports and mortality will be performed. The confounders included in the multivariable analysis are as follows: 1) known risk factors for mortality (age, sex, and hypertension); 2) the severity of the acute illness 24 hours before the targeted respiratory support (Sequential Organ Failure Assessment score and Glasgow Coma Scale score); 3) the various phases during the first pandemic year, including the first phase (February 1, 2020, to May 31, 2020), the second phase (June 1, 2020, to August 31, 2020), the third phase (September 1, 2020, to November 30, 2020), and the fourth phase (December 1, 2020, to last date of data extraction); 4) the demographics and comorbidities with a P-value < 0.25 in the univariate analysis; and 5) the laboratory results and vital signs 24 hours before the targeted respiratory support that have a P-value < 0.25 in the univariate analysis. All treatments considered to be part of COVID-19 management will be included in the multivariable analysis for confounding control. To avoid collinearity, only one variable will be included if two variables have an absolute Pearson's or Spearman's rank correlation coefficient greater than 0.5. Variables with more than 10% missing data will also be excluded. Multiple testing will be corrected using the Bonferroni method to reduce the chance of type I error at a two-sided 0.05 alpha level, considering the hypotheses for all of the COVID-19-related respiratory supports/treatments as a family. The association between exposures and mortality will be estimated using hazard ratios (HRs) and reported with 95% confidence intervals (CIs). To account for clustering within hospitals, robust sandwich estimators to compute standard errors for the HRs will be used. The proportional hazards assumption will be assessed using Schoenfeld residuals.

With a two-tailed hypothesis test, the significance level for each general hypothesis is 0.05. All analyses will be performed in R software (version 3.5.3, R Foundation for Statistical Computing).

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.
Observational

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.
2300

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

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale University School of Medicine

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

Sampling Method

Non-Probability Sample

Study Population

All COVID-19 patients treated in the ICUs in Yale New Haven Health System throughout the first pandemic year

Description

Inclusion Criteria:

  • All COVID-19 patients treated in the ICUs in Yale New Haven Health System throughout the first pandemic year

Exclusion Criteria:

  • None

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

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 in-hospital mortality
Time Frame: through study completion, an average of 11 days
the number of all-cause death during hospitalization divided by the number of patients who were discharged from hospital or remained hospitalized but alive on the last day of data extraction
through study completion, an average of 11 days

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
rate of escalation from non-invasive ventilation to invasive mechanical ventilation
Time Frame: through study completion, an average of 11 days
the number of patients who require respiratory support escalation from non-invasive ventilation to invasive mechanical ventilation divided by the number of patients who require non-invasive ventilation disregarding the requirement of escalation
through study completion, an average of 11 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.
Yale University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Kimberly Kunze, Yale 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.
April 1, 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.
April 20, 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.
April 20, 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).
March 29, 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.
April 2, 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.
April 5, 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.
May 13, 2021

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.
May 10, 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.
May 1, 2021

More Information

Terms related to this study

Keywords

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.
  • 2000028070

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Institutional approval is required for patient data sharing.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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