Back to results

Early PReserved SPONtaneous Breathing Activity in Mechanically Ventilated Patients With ARDS (PReSPON) (PReSPON)

Primary Purpose

Respiratory Distress Syndrome, Adult

Status

Recruiting

Phase

Not Applicable

Locations

Germany

Study Type

Interventional

Intervention

spontaneous breathing activity during APRV

No spontaneous breathing activity

About this trial

This is an interventional treatment trial for Respiratory Distress Syndrome, Adult focused on measuring Airway Pressure Release Ventilation, Bilevel Continuous Positive Airway Pressure, Biphasic Continuous Positive Airway Pressure, Mechanical Ventilation, Ventilator-Induced Lung Injury, Spontaneous Breathing

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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)
Requirement for positive pressure ventilation via an endotracheal tube/ tracheotomy
Presence of informed consent according to local regulations
Age ≥ 18 years
Expected duration of mechanical ventilation > 48 hours at randomization

Exclusion Criteria:

Need of extracorporeal lung support, high frequency oscillation and/or inhaled vasodilators for severe hypoxemia prior to inclusion
Woman known to be pregnant, lactating or having a positive or indeterminate pregnancy test
Neuromuscular disease that impairs ability to ventilate spontaneously
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
Chronic kidney disease stage V (requirement of dialysis) according to the K/DOQI definition of chronic kidney disease
Massive diffuse alveolar haemorrhage
Recent lung transplant < 12 months
Morbid obesity defined as weight greater than 1 kg / cm
Burns > 70% total body surface
Suspected or known elevated intracranial pressure
Chronic liver disease (Child-Pugh grade C)
Ongoing chemotherapy and/or bone marrow transplantation within the last 3 months
Moribund patient not expected to survive 48 hours
Patients not expected to survive 90 days on the basis of the premorbid health status
Patient, surrogate, or physician not committed to full life support

Sites / Locations

University Hospital Bonn, Department of Anesthesiology and Critical Care MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Spontaneous Breathing Group

Controlled Mechanical Ventilation Group

Arm Description

Spontaneous breathing activity will be allowed during APRV within one hour after randomization throughout the first 48 hours. After 48 hours, standard routine care should be provided in both groups, although we suggest moderate sedation while spontaneous breathing is maintained with APRV, pressure support ventilation (PSV), or other assisting ventilator modes. Weaning off mechanical ventilation will be performed after 48 hours according to a protocol using spontaneous breathing trials.

Pressure controlled mechanical ventilation will be applied throughout the first 48 hours. After 48 hours, standard routine care should be provided in both groups, although we suggest moderate sedation while spontaneous breathing is maintained with APRV, pressure support ventilation (PSV), or other assisting ventilator modes. Weaning off mechanical ventilation will be performed after 48 hours according to a protocol using spontaneous breathing trials.

Outcomes

Primary Outcome Measures

All-cause mortality at study day 28 (D28)

All-cause mortality at D28 will be defined as number of patients deceased at D28 divided by number of all patients. In case of missing survival status in more than 1% of the patients, additional analyses will be carried out using multiple imputation or estimating-equation methods. The date of death will be recorded for all patients who die. Up to D28, the patient's location at the time of death (ICU or hospital) will also be recorded.

Number of Ventilator Free Days (VFD) until day 28 (D28)

Number of VFDs until D28 are defined as number of days alive and completely off the ventilator until day 28. A patient will be reported as ventilator free after two consecutive calendar days of unassisted spontaneous breathing (UAB). UAB is defined as: Spontaneously breathing with face mask, nasal prong oxygen or room air T-piece breathing Tracheostomy breathing CPAP ≤5 cmH2O without pressure support or another mode of assisted mechanical ventilation Use of CPAP or BIPAP solely for sleep apnoea management Patients still on positive pressure ventilation/receiving assisted breathing who are transferred to another hospital or healthcare facility prior to D28 will be followed up to assess the VFD outcome at D28.

Secondary Outcome Measures

All-Cause Mortality Rate at study day 90 (D90)

All-cause mortality at D90 is defined as number of patients deceased at D90 divided by number of all patients. Patients with missing survival status will be counted as non-survivor.

Number of Vasoactive Drug Free Days until study day 28 (D28)

Number vasoactive drug free days are defined as number of days alive and completely off the vasoactive drugs until D28. Any vasoactive support given to the patient will be recorded in the e-CRF. Vasoactive support includes: catecholamine and non-catecholamine vasopressors, inotropes and vasodilating agents.

Number of Renal Support Free Days until study day 28 (D28)

Number of Renal Support Free Days are defined as number of days alive and completely off the renal support until day 28. Any renal support given to the patient will be recorded on a specific page in the e-CRF.

Sequential Organ Failure Assessment (SOFA)

Organ failure status will be assessed using the mean SOFA score, which assesses six organ systems: respiration, coagulation, liver, cardiovascular, central nervous system and renal function. A patient will be defined as being free of organ failure when the SOFA score is zero.

Full Information

NCT ID

NCT04228471

First Posted

December 19, 2019

Last Updated

February 8, 2021

Sponsor

University Hospital, Bonn

Collaborators

European Society of Anaesthesiology

1. Study Identification

Unique Protocol Identification Number

NCT04228471

Brief Title

Early PReserved SPONtaneous Breathing Activity in Mechanically Ventilated Patients With ARDS (PReSPON)

Acronym

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

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Recruiting

Study Start Date

February 8, 2020 (Actual)

Primary Completion Date

February 2024 (Anticipated)

Study Completion Date

July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University Hospital, Bonn

Collaborators

European Society of Anaesthesiology

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

InvestigatorOutcomes Assessor

Masking Description

Double

Allocation

Randomized

Enrollment

840 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Spontaneous Breathing Group

Arm Type

Experimental

Arm Description

Arm Title

Controlled Mechanical Ventilation Group

Arm Type

Experimental

Arm Description

Intervention Type

Procedure

Intervention Name(s)

spontaneous breathing activity during APRV

Intervention Description

Allowing spontaneous breathing activity with APRV throughout the first 48 hours.

Intervention Type

Procedure

Intervention Name(s)

No spontaneous breathing activity

Intervention Description

No spontaneous breathing activity will be allowed with pressure controlled ventilation throughout the first 48 hours.

Primary Outcome Measure Information:

Title

All-cause mortality at study day 28 (D28)

Description

Time Frame

All-cause mortality at D28 will be defined as number of patients who deceased at day 28.

Title

Number of Ventilator Free Days (VFD) until day 28 (D28)

Description

Time Frame

Number of Ventilator Free Days will be measured until day 28.

Secondary Outcome Measure Information:

Title

All-Cause Mortality Rate at study day 90 (D90)

Description

All-cause mortality at D90 is defined as number of patients deceased at D90 divided by number of all patients. Patients with missing survival status will be counted as non-survivor.

Time Frame

All-cause mortality at D90 will be defined as number of patients who deceased at day 90.

Title

Number of Vasoactive Drug Free Days until study day 28 (D28)

Description

Time Frame

Number of Vasoactive Drug Free Days will be measured until D28.

Title

Number of Renal Support Free Days until study day 28 (D28)

Description

Time Frame

Number of Renal Support Free Days will be measured until study day 28.

Title

Sequential Organ Failure Assessment (SOFA)

Description

Time Frame

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 Pre-specified Outcome Measures:

Title

Level of Sedation until study day 7 (D7)

Description

Level of Sedation will be determined using the Ramsay scale [minimum value: 1 (anxious, agitated, restless) to 6 (no response to light glabellar tap or loud auditory stimulus)], the Richmond Agitation- Sedation Scale [minimum value: -5 (unarousable) to +4 (combative)], or the Riker Sedation-Agitation Scale [minimum value: 1 (unarousable) to 7 (dangerous agitation)]. Sedation/analgesia according to local standard will be titrated to achieve either a deep or a moderate sedation level. Deep sedation is defined as a Ramsay score of 5 to 6, which corresponds to a Richmond Agitation-Sedation Scale (RASS) of -4 to -5 or a Riker Sedation-Agitation Scale of 1 to 2. Moderate sedation is defined as a Ramsay score of 2 to 3, which corresponds to a RASS of 0 to -1 or a Riker Sedation-Agitation Scale of 3 to 4.

Time Frame

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.

Title

Level of Analgesia until study day 7 (D7)

Description

Level of analgesia will be determined using the Behavioural Pain Scale for pain assessment in intubated patients. The Behavioral Pain Scale quantifies pain using body language and patient-ventilator interactions for intubated patients. Minimum value: 3 (calm, no pain), maximum value: 12 (maximum pain, restless).

Time Frame

The distribution of Behavioural Pain Scale will be described for each study day until D7.

Title

Occurrence of barotrauma w/o Chest Tube until ICU discharge or study day 28 (D28)

Description

Barotrauma will be defined as newly developed pneumothorax, pneumomediastinum, subcutaneous emphysema, or pneumatocele larger than 2 cm in diameter with and without a chest tube and will be reported as adverse event (AE).

Time Frame

The number of patients with barotrauma will be counted until ICU discharge or D28 whatever comes first.

Title

Occurrence of pneumonia until ICU discharge or study day (D28)

Description

Any newly acquired pneumonia either microbiologically confirmed or radiologically and clinically suspected by the American Thoracic Society definition requiring antimicrobial treatment.

Time Frame

Will be counted until ICU discharge or D28 whatever comes first.

Title

Weaning Failure until study day 28 (D28)

Description

Weaning failure will be reported as failure to pass SBTs until D28. The proportion of patients with weaning failure will be analyzed.

Time Frame

Will be measured until D28.

Title

Use of Prone Positioning until study day 28 (D28)

Description

Prone positioning will be recorded until study day 28 (D28). The proportion of patients with prone positioning will be analyzed.

Time Frame

Will be counted until D28.

Title

Use of Extra-corporeal Membrane Oxygenation (ECMO) as a rescue therapy until study day 28 (D28)

Description

In refractory hypoxemia (PaO2/FIO2 < 60 mmHg) and in patients who do not respond with a substantial increase in arterial oxygenation in the transition from lower to higher PEEP a rescue therapy is allowed. The proportion of patients with Extra-corporeal Membrane Oxygenation (ECMO) will be analyzed.

Time Frame

Use of Extra-corporeal Membrane Oxygenation (ECMO) will be counted until study day 28 (D28).

Title

Use of an inhaled vasodilator (e.g. inhaled nitric oxide) as a rescue therapy until study day 28 (D28)

Description

In refractory hypoxemia (PaO2/FIO2 < 60 mmHg) and in patients who do not respond with a substantial increase in arterial oxygenation in the transition from lower to higher PEEP a rescue therapy is allowed. The proportion of patients with the use of an inhaled vasodilator will be analyzed.

Time Frame

Use of an inhaled vasodilator will be counted until study day 28 (D28).

Title

Use of an neuromuscular blocking agent (NMBA) (if not in the Control Group) as a rescue therapy until study day 28 (D28)

Description

In refractory hypoxemia (PaO2/FIO2 < 60 mmHg) and in patients who do not respond with a substantial increase in arterial oxygenation in the transition from lower to higher PEEP a rescue therapy is allowed. The proportion of patients with the use of an neuromuscular blocking agent (NMBA) (if not in the Control Group) will be analyzed.

Time Frame

Use of an neuromuscular blocking agent (NMBA) (if not in the Control Group) will be counted until study day 28 (D28).

Title

Use of high-frequency oscillation as a rescue therapy until study day 28 (D28)

Description

In refractory hypoxemia (PaO2/FIO2 < 60 mmHg) and in patients who do not respond with a substantial increase in arterial oxygenation in the transition from lower to higher PEEP a rescue therapy is allowed. The proportion of patients with the use of high-frequency oscillation will be analyzed.

Time Frame

Use of high-frequency oscillation will be counted until study day 28 (D28).

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Moderate to severe ARDS for ≤ 48 hours according to the Berlin definition will be defined by acute onset of: PaO2/FiO2 ≤ 200 mmHg (equivalent to ≤ 26.7 kPa) under invasive mechanical ventilation with PEEP ≥ 5 cmH2O Bilateral infiltrates documented by chest radiograph Not fully explained by cardiac failure or fluid overload (e.g. echocardiography) Requirement for positive pressure ventilation via an endotracheal tube/ tracheotomy Presence of informed consent according to local regulations Age ≥ 18 years Expected duration of mechanical ventilation > 48 hours at randomization Exclusion Criteria: Need of extracorporeal lung support, high frequency oscillation and/or inhaled vasodilators for severe hypoxemia prior to inclusion Woman known to be pregnant, lactating or having a positive or indeterminate pregnancy test Neuromuscular disease that impairs ability to ventilate spontaneously 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 Chronic kidney disease stage V (requirement of dialysis) according to the K/DOQI definition of chronic kidney disease Massive diffuse alveolar haemorrhage Recent lung transplant < 12 months Morbid obesity defined as weight greater than 1 kg / cm Burns > 70% total body surface Suspected or known elevated intracranial pressure Chronic liver disease (Child-Pugh grade C) Ongoing chemotherapy and/or bone marrow transplantation within the last 3 months Moribund patient not expected to survive 48 hours Patients not expected to survive 90 days on the basis of the premorbid health status Patient, surrogate, or physician not committed to full life support

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Christian Putensen, M.D., PhD.

Phone

+49 228 287

Ext

14119

Christian.Putensen@ukbonn.de

First Name & Middle Initial & Last Name or Official Title & Degree

Stefan Muenster, M.D.

Phone

+49 228 287

Ext

14119

Stefan.Muenster@ukbonn.de

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Christian Putensen, M.D., PhD.

Organizational Affiliation

University Hospital, Bonn

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospital Bonn, Department of Anesthesiology and Critical Care Medicine

City

Bonn

ZIP/Postal Code

53127

Country

Germany

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Christian Putensen, MD, PhD

Phone

+4922828714119

christian.putensen@ukbonn.de

First Name & Middle Initial & Last Name & Degree

Stefan Muenster, MD

Phone

+4922828714119

stefan.muenster@ukbonn.de

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

Early PReserved SPONtaneous Breathing Activity in Mechanically Ventilated Patients With ARDS (PReSPON)

We'll reach out to this number within 24 hrs