Clinical trial NCT04369274: Repeated Measures Trial of Temporary Automated Manual Ventilation Versus Noninvasive Oxygenation or Conventional Vent
Official title: A Repeated Measures Trial of Temporary Automated Manual Ventilation Versus Noninvasive Oxygenation or Conventional Ventilation for the Treatment of COVID-19 ARDS
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Respiratory Failure
Keywords: mechanical ventilator
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2020-04-30
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Arterial oxygenation
timeFrame: Measurement 10 minutes after onset of initial period of automatic compressed ventilations
measure: Arterial oxygenation
timeFrame: Measurement 20 minutes after onset of second period of automatic compressed ventilations
Secondary outcomes:
measure: Expired pressure of carbon dioxide.
timeFrame: 2 hour total study period.
measure: Airway pressure
timeFrame: 2 hour total study period.
measure: Heart rate
timeFrame: 2 hour total study period.
measure: Blood pressure
timeFrame: 2 hour total study period.
measure: Airway flow
timeFrame: 2 hour total study period.
Other outcomes:
measure: Mortality
timeFrame: Duration of hospitalization, up to 2 months
Locations:
Study officials:
affiliation: Massachusetts General Hospital
name: Keith A Marill, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.