Clinical Evaluation of an Airborne Pathogen Containment Device: Randomized Open-label Equivalence Trial During Endotracheal Intubation

Background and Rationale Pandemic spread of COVID-19 presents an unprecedented challenge for health care systems around the world. A highly infectious respiratory virus with long incubation, asymptomatic transmission and environmental stability, SARS-CoV-2 places health care workers (HCWs) at risk of contracting the infection and transmitting it to patients. The early problems with personal protective equipment (PPE) supply have led to a renewed urgency to develop a number of different layers of mitigation. Together, these would offer equitable protection and rational supply management. Central to PPE use are questions related to the type (droplets, aerosol or contact) and magnitude (viral load) of the risk in specific situations. Given the unprecedented transmissibility of the newer variants, there is an interest in further mitigating potential exposure. This would be particularly relevant for procedures that limit ability to apply source control such as masking the infectious individual.

Transmission of SARS-CoV-2 is currently understood to occur primarily by respiratory droplets (> 20 microns in diameter), aerosols (\< 5 microns) and direct mucosal contact with respiratory secretions. While aerosolization during aerosol generating medical procedures (AGMP) is still a significant focus of infection control protocols, it is increasingly clear that physiologic aerosolization is at least as important. Aerosols containing viral particles can remain suspended and viable in the air for up to 3 hours under experimental conditions. They can be carried by airstream and, when inhaled, be deposited into the lungs as deep as the alveoli. In the setting of perioperative care, AGMPs are administration of oxygen by high-flow nasal cannula, non-invasive positive pressure ventilation, endotracheal intubation and extubation. To minimize aerosol contamination of the facility, Canadian Anesthesiologists' Society and American Society of Anesthesiologists recommend that airway management should ideally be performed in a negative pressure room, while avoiding direct flow of pressurized gas into the patient's airway. This is achieved by limiting flow rate during preoxygenation, ensuring deep muscle relaxation to avoid cough, applying a HEPA filter to the endotracheal tube and inflating the tracheal cuff prior to connecting the ventilator circuit. Very few operating rooms in Canada (and worldwide) are built as isolation rooms. Furthermore, the risk to HCWs who are in the immediate vicinity of the source, performing the procedure, is however, minimally mitigated by these measures.

The ability to apply source control and contain the spread of aerosol at the time of AGMP including extubation would ensure timely patient care without compromising HCW safety and with minimal risk of facility contamination. Several improvised passive intubation shields or boxes have been reported, with significant limitations that make them likely ineffective and potentially harmful. The research proposed in this application builds on our original device design that has addressed the shortcomings of aerosol boxes. This study will provide much needed knowledge about safe clinical use to build on the research team's simulation trials (research funded by the IWK Research Foundation Project Grant).

The device is designed to: (1) be simple and intuitive to use (2) be portable and rapidly deployed (3) provide ergonomic operator access (4) contain the spread of aerosols (5) permanently trap contaminants while minimizing the risk of aerosol resuspension during removal and room cleaning (6) be easily and safely disposed of and (7) inexpensive. Previous testing of the ease of use, potential safety implications and the impact on facility contamination has provided evidence that informs clinical evaluation in this study. Study findings may extend to health system management, public health response, decision-making and planning within and across jurisdictions in Canada and internationally.

This equivalence trial will aim to determine whether intubation with the flexible, disposable, active aerosol containment device is similar to intubation without the enclosure device with respect to intubation times, secondary safety endpoint and exploratory endpoints representing patient and anesthesiologist experiences and perceptions.

Objectives

The trial objective is to test ease of use in the operating room environment and patient safety (as indicated by the time to airway placement and change in oxygen saturation) of prototype (model versions 2 and 3, see description below) of an airborne pathogen containment device intended to decrease viral contamination during airway management. The testing will address the following research questions centered on the effect of physical presence of the device during the intubation process:

Q1: What is the difference in time to placement of airway (ta) with and without the containment device? Q2: Is the change in physiologic parameters upon airway placement significantly different in the presence of the device? [13][14] Q3: Does the use of the device affect the first attempt airway placement success rate? Q4: What is the impact on patients' and anesthesiologists' experience and satisfaction?

Trial endpoints Primary endpoint: Intubation times The null hypothesis states that intubation times with (experimental group) and without the containment device (standard treatment) differ by more than the equivalence margin of 10% (see sample size calculation).

Secondary endpoint: the number of patients experiencing either of the 2 co-secondary endpoints.

Co-secondary endpoint 1: Number of patients with post-intubation SaO2 \<90% Co-secondary endpoint 2: The number of intubations requiring more than one attempt The 2 endpoints are not independent: requiring additional intubation attempts may lead to low SaO2 and positive pressure ventilation to maintain SaO2. Conversely, unduly persisting in 1st attempt may lead to low SaO2. These endpoints are thus complementary in capturing the potential effect of containment device. The benefit of combining them is avoidance of inflating the Type II error rate in controlling false discovery rate (which would be necessary with multiple endpoints).

The null hypothesis is that the number of patients with significant desaturation and/or multiple attempts will differ by more than the equivalence margin (see sample size calculation).

Exploratory endpoint 1: Absolute pre-post intubation change in end-tidal oxygen (change in ETCO2) Exploratory endpoint 2: Mean patient visual analogue scale (VAS) satisfaction score with the experience of "going to sleep" Exploratory endpoint 3: Mean anesthesiologist VAS "ease of airway management score"

Declaring device "success" or "failure" The trial can declare equivalence ("success") if statistical evidence is found to reject the null hypothesis for the primary endpoint of > 10% difference (equivalence margin) in intubation times.

It is, however, possible that the device does not meet the primary endpoint (the difference between intubation times is greater than the prespecified equivalence margin), but that the overall intubation times (at least 90% of the intubations) with device in place are within 60 seconds - a generally accepted "safe" intubation time. In this event, the device can still be deemed successful provided it meets the secondary (safety) endpoint. The secondary endpoint combines indicators that reflect adverse consequences of prolonged intubation time.

In the event that neither the primary nor the secondary endpoints are met, the device will have "failed" the clinical trial. The acquired data including exploratory endpoints and survey data will be reviewed and used to identify problems and, if possible, address them through device re-design.