Repeated Measures Trial of Temporary Automated Manual Ventilation Versus Noninvasive Oxygenation or Conventional Vent

A Repeated Measures Trial of Temporary Automated Manual Ventilation Versus Noninvasive Oxygenation or Conventional Ventilation for the Treatment of COVID-19 ARDS

The COVID-19 pandemic has led to a potential shortage of life-saving mechanical ventilators. The purpose of this study is to determine whether a novel simpler to device, the automated bag-valve-mask (BVM) compressor, can be used to provide assisted ventilation temporarily to patients in need. This includes patients with COVID-19 lung infection and respiratory failure. If successful, this would increase the pool of total available ventilator hours to alleviate any shortage.

Study Overview

• Status: Withdrawn
• Conditions: Respiratory Failure
• Intervention / Treatment: Device: Mechanical ventilation with the automated BVM compressor

Detailed Description

This study will be performed in the emergency department and ICU's of Massachusetts General Hospital (MGH). Thirty patients requiring mechanical ventilation will be enrolled. The design is a case series with repeated measures analysis. All patients will receive the experimental treatment as well as conventional ventilation and unassisted oxygenation as observed prior to initiation of mechanical ventilation. The compressor used will be manufactured by Spiro LLC / 10xbeta based on the open source MIT design. The device is powered by an uninterrupted power supply from a standard electrical outlet and it alarms if unplugged.

The patient will be moved into a negative pressure room. After patients with respiratory failure are intubated and stabilized on a conventional ventilator, they will receive 15 minutes of artificial respirations with the automated compressor with the conventional ventilator standing by. They will be returned to the conventional respirator after this period, or sooner if necessary. The endotracheal tube will be briefly clamped during the rapid transition from one device to another to minimize aerosolization of any viral particles and to retain any PEEP.

If the initial study period demonstrates successful respiratory support, then the procedure may be repeated once with doubling of the automated compressor treatment time to 30 minutes. There will be a minimum 15-minute observation period with conventional mechanical ventilation between the two study periods. Additionally, there will be one hour of data collection after the study periods. The total duration of the two intervention periods, the intervening period and data collection is two hours. The primary outcome is arterial oxygenation.

Patients are chemically paralyzed to facilitate intubation as part of standard care. Rocuronium is typically used for intubating chemical paralysis in the MGH emergency department. It has a half-life of 66 minutes. A single repeat bolus will be provided if needed to ensure chemical paralysis for the duration of the study. If the patient is already intubated and no longer chemically paralyzed, than one bolus of rocuronium, and a second as needed, or just a temporary increase in ongoing sedation will be provided to minimize spontaneous respiration. The airway circuit will be continuously monitored with a separate pressure and flow monitor (Nico) with recorded digital output throughout the experiment.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Keith A Marill, MD; Phone Number: 617-643-8595; Email: kmarill@mgh.harvard.edu
• Study Contact Backup: Name: Blair Parry, CCRC; Phone Number: 617-724-4759; Email: bparry@mgh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient may be diagnosed with Covid-19 based on clinical presentation and available laboratory studies including specific Covid-19 testing.
• Patient with imminent respiratory failure or status post respiratory failure receiving mechanical ventilation, or requiring mechanical ventilation for airway protection or other cause.

• Evidence of no pulmonary disease, or mild to moderate ARDS based on:

  • fraction of inspired oxygen (FiO2) ≤ 60% with arterial oxygen saturation > 90%
  • positive end expiratory pressure (PEEP) ≤ 12 cm H20
• Using an adaptive trial design, the first 10 patients must require mechanical ventilation for reasons other than COVID-19 infection such as airway protection due to overdose, seizure, stroke, or trauma. The next 10 patients may have COVID-19 infection, but must demonstrate lung compliance ≥ 40 ml/cm H2O. If these 10 patients demonstrate a satisfactory course associated with treatment, then the final 10 patients may have lung compliance ≥ 30 ml/cm H2O. Satisfactory treatment course will include, at a minimum: oxygen saturation > 90%, with PEEP ≤ 12 cm H2O.

Exclusion Criteria:

• Lack of informed consent from patient, if deemed having capacity, or from surrogate if not
• Too medically unstable to participate in study per treating clinician
• Patients requiring more than one vasopressor medication for blood pressure support
• Age > 65 years
• Clinical evidence of acute coronary syndrome (ACS) including angina, or ECG evidence of acute ischemia or dysrhythmia
• Chronic lung disease including chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, or pulmonary hypertension
• Gross laboratory abnormalities including, when available: liver function tests (LFT) > 5x normal, C-reactive protein (CRP) > 200 mg/L, ferritin > 2000 µg/L, creatine phosphokinase (CPK) > 3x normal, D-Dimer > 2500 ng/ml
• Previously enrolled subject
• Children
• Pregnant women
• Estimated body mass index (BMI) greater than 30
• Prisoners

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interventional; All subjects will briefly be placed on the automated BVM compressor device. Measurements obtained while on this device will be compared to those obtained in the same subject prior to mechanical ventilation and while on a conventional ventilator.	Device: Mechanical ventilation with the automated BVM compressor; Mechanical ventilation is accomplished with a device that mechanically squeezes a manual bag valve instead of by hand. The rate and volume of compression are adjustable, and the device has appropriate alarms and safety features.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arterial oxygenation	Arterial oxygenation obtained as measured by noninvasive pulse oximetry and arterial blood gas.	Measurement 10 minutes after onset of initial period of automatic compressed ventilations
Arterial oxygenation	Arterial oxygenation obtained as measured by noninvasive pulse oximetry and arterial blood gas.	Measurement 20 minutes after onset of second period of automatic compressed ventilations

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expired pressure of carbon dioxide.	Expired carbon dioxide (CO2) pressure will be measured continuously with a monitor in the airway circuit.	2 hour total study period.
Airway pressure	The pressure (cm H2O) of inspired and expired air in the airway circuit while the subject is mechanically ventilated will be measured continuously using a Nico monitor.	2 hour total study period.
Heart rate	Subject heart rate (beats per minute) will be measured continuously using a telemetry monitor,	2 hour total study period.
Blood pressure	Subject blood pressure (mm Hg) will be measured episodically every 5 minutes using an automated arm cuff.	2 hour total study period.
Airway flow	The flow (L/min) of inspired and expired air in the airway circuit while the subject is mechanically ventilated will be measured continuously using a Nico monitor.	2 hour total study period.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	The subject will be followed clinically to assess for recovery and survival or death.	Duration of hospitalization, up to 2 months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Keith A Marill, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Al Husseini AM, Lee HJ, Negrete J, Powelson S, Servi AT, Slocum AH, Saukkonen J. Design and Prototyping of a Low-Cost Portable Mechanical Ventilator. J Med Device. 2010 Jun 1;4(2):027514. doi: 10.1115/1.3442790. Epub 2010 Aug 9.

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2022
• Primary Completion (Anticipated): November 1, 2023
• Study Completion (Anticipated): November 1, 2023

Study Registration Dates

• First Submitted: April 23, 2020
• First Submitted That Met QC Criteria: April 27, 2020
• First Posted (Actual): April 30, 2020

Study Record Updates

• Last Update Posted (Actual): March 15, 2023
• Last Update Submitted That Met QC Criteria: March 14, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: mechanical ventilator
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency
• Other Study ID Numbers: 2020P001051

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes