Clinical trial NCT04228471: Early PReserved SPONtaneous Breathing Activity in Mechanically Ventilated Patients With ARDS (PReSPON)
Official title: Early PReserved SPONtaneous Breathing Activity in Mechanically Ventilated Patients With Acute Respiratory Distress Syndrome - The PReSPON Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Respiratory Distress Syndrome, Adult
Keywords: Airway Pressure Release Ventilation
Bilevel Continuous Positive Airway Pressure
Biphasic Continuous Positive Airway Pressure
Mechanical Ventilation
Ventilator-Induced Lung Injury
Spontaneous Breathing
Lead sponsor: University Hospital, Bonn
Sponsor class: OTHER
Collaborators: name: European Society of Anaesthesiology
First posted: 2020-01-14
Enrollment: 840
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The potential benefits of preserved early spontaneous breathing activity during mechanical ventilation are an increased aeration of dependent lung regions, less need for sedation, improved cardiac filling, and better matching of pulmonary ventilation and perfusion and thus oxygenation. Two small randomized controlled trials (RCTs) in patients with acute respiratory distress syndrome (ARDS) reported less time on mechanical ventilation and in the intensive care unit (ICU) with preserved early spontaneous breathing activity during Airway Pressure Release Ventilation (APRV).

Debate exists over the net effects of preserved early spontaneous breathing activity with regard to ventilator-associated lung injury (VALI). In fact, by taking advantage of the potential improvement in oxygenation and recruitment at lower inflation pressures associated with APRV, physicians could possibly reduce potentially harmful levels of inspired oxygen, tidal volume, and positive end-expiratory pressure (PEEP). However, spontaneous breathing during mechanical ventilation has the potential to generate less positive pleural pressures that may add to the alveolar stretch applied from the ventilator and contribute to the risk of VALI. This has led to an ongoing controversy whether an initial period of controlled mechanical ventilation with deep sedation and neuromuscular blockade or preserved early spontaneous breathing activity during mechanical ventilation is advantageous with respect to outcomes in ARDS patients.

A RCT investigating the effects of early spontaneous breathing activity on mortality in moderate to severe ARDS has been highly recommended in the research agenda for intensive care medicine.

The objective of this study is to evaluate the efficacy and safety of preserved spontaneous breathing activity during APRV in the early phase of moderate to severe ARDS.


Eligibility criteria: Inclusion Criteria:

1. Moderate to severe ARDS for ≤ 48 hours according to the Berlin definition will be defined by acute onset of:

   1. PaO2/FiO2 ≤ 200 mmHg (equivalent to ≤ 26.7 kPa) under invasive mechanical ventilation with PEEP ≥ 5 cmH2O
   2. Bilateral infiltrates documented by chest radiograph
   3. Not fully explained by cardiac failure or fluid overload (e.g. echocardiography)
2. Requirement for positive pressure ventilation via an endotracheal tube/ tracheotomy
3. Presence of informed consent according to local regulations
4. Age ≥ 18 years
5. Expected duration of mechanical ventilation \> 48 hours at randomization

Exclusion Criteria:

1. Need of extracorporeal lung support, high frequency oscillation and/or inhaled vasodilators for severe hypoxemia prior to inclusion
2. Woman known to be pregnant, lactating or having a positive or indeterminate pregnancy test
3. Neuromuscular disease that impairs ability to ventilate spontaneously
4. Severe chronic respiratory disease (e.g. COPD, pulmonary fibrosis, and other chronic diseases of the lung, chest wall or neuromuscular system) requiring home oxygen therapy or mechanical ventilation (non-invasive ventilation or via tracheotomy) except for Continuous Positive Airway Pressure (CPAP) or non-invasive Biphasic Positive Airway Pressure (BiPAP) used solely for sleep-disordered breathing
5. Chronic kidney disease stage V (requirement of dialysis) according to the K/DOQI definition of chronic kidney disease
6. Massive diffuse alveolar haemorrhage
7. Recent lung transplant \< 12 months
8. Morbid obesity defined as weight greater than 1 kg / cm
9. Burns \> 70% total body surface
10. Suspected or known elevated intracranial pressure
11. Chronic liver disease (Child-Pugh grade C)
12. Ongoing chemotherapy and/or bone marrow transplantation within the last 3 months
13. Moribund patient not expected to survive 48 hours
14. Patients not expected to survive 90 days on the basis of the premorbid health status
15. Patient, surrogate, or physician not committed to full life support

Primary outcomes:
measure: All-cause mortality at study day 28 (D28)
timeFrame: All-cause mortality at D28 will be defined as number of patients who deceased at day 28.
measure: Number of Ventilator Free Days (VFD) until day 28 (D28)
timeFrame: Number of Ventilator Free Days will be measured until day 28.
Secondary outcomes:
measure: All-Cause Mortality Rate at study day 90 (D90)
timeFrame: All-cause mortality at D90 will be defined as number of patients who deceased at day 90.
measure: Number of Vasoactive Drug Free Days until study day 28 (D28)
timeFrame: Number of Vasoactive Drug Free Days will be measured until D28.
measure: Number of Renal Support Free Days until study day 28 (D28)
timeFrame: Number of Renal Support Free Days will be measured until study day 28.
measure: Sequential Organ Failure Assessment (SOFA)
timeFrame: The score will be assessed pre-randomization on study day 1 (D1) and daily up to study day 7 (D7) and while the patient is in the ICU until D28.
Other outcomes:
measure: Level of Sedation until study day 7 (D7)
timeFrame: For each study day, the distribution of Ramsay scale, Richmond Agitation-Sedation Scale, or Riker Sedation-Agitation Scale and the number of patients deviating from the target will be described until D7.
measure: Level of Analgesia until study day 7 (D7)
timeFrame: The distribution of Behavioural Pain Scale will be described for each study day until D7.
measure: Occurrence of barotrauma w/o Chest Tube until ICU discharge or study day 28 (D28)
timeFrame: The number of patients with barotrauma will be counted until ICU discharge or D28 whatever comes first.
measure: Occurrence of pneumonia until ICU discharge or study day (D28)
timeFrame: Will be counted until ICU discharge or D28 whatever comes first.
measure: Weaning Failure until study day 28 (D28)
timeFrame: Will be measured until D28.
measure: Use of Prone Positioning until study day 28 (D28)
timeFrame: Will be counted until D28.
measure: Use of Extra-corporeal Membrane Oxygenation (ECMO) as a rescue therapy until study day 28 (D28)
timeFrame: Use of Extra-corporeal Membrane Oxygenation (ECMO) will be counted until study day 28 (D28).
measure: Use of an inhaled vasodilator (e.g. inhaled nitric oxide) as a rescue therapy until study day 28 (D28)
timeFrame: Use of an inhaled vasodilator will be counted until study day 28 (D28).
measure: Use of an neuromuscular blocking agent (NMBA) (if not in the Control Group) as a rescue therapy until study day 28 (D28)
timeFrame: Use of an neuromuscular blocking agent (NMBA) (if not in the Control Group) will be counted until study day 28 (D28).
measure: Use of high-frequency oscillation as a rescue therapy until study day 28 (D28)
timeFrame: Use of high-frequency oscillation will be counted until study day 28 (D28).
Locations:
city: Bonn
country: Germany
facility: University Hospital Bonn, Department of Anesthesiology and Critical Care Medicine
Study officials:
affiliation: University Hospital, Bonn
name: Christian Putensen, M.D., PhD.
role: PRINCIPAL_INVESTIGATOR
References: