Respiratory Distress Syndrome, AdultPReSPONNCT04228471
Early PReserved SPONtaneous Breathing Activity in Mechanically Ventilated Patients With ARDS (PReSPON)
A study testing spontaneous breathing activity during APRV and No spontaneous breathing activity in people with Respiratory Distress Syndrome, Adult, run by University Hospital, Bonn at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Respiratory Distress Syndrome, Adult
- What is being tested?
- spontaneous breathing activity during APRV and No spontaneous breathing activity
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 840 participants
- Where
- 1 siteGermany
- Study dates
- 8 Feb 2020to Jul 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
University Hospital Bonn, Department of Anesthesiology and Critical Care Medicine
Bonn, 53127
Christian Putensen, MD, PhD, +4922828714119, christian.putensen@ukbonn.de
Stefan Muenster, MD, +4922828714119, stefan.muenster@ukbonn.de
About this study
Official title: Early PReserved SPONtaneous Breathing Activity in Mechanically Ventilated Patients With Acute Respiratory Distress Syndrome - The PReSPON Randomized Controlled Trial
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.
Read more
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.
- Conditions
- Respiratory Distress Syndrome, Adult
- Being tested
- spontaneous breathing activity during APRV, No spontaneous breathing activity
- Keywords
- Airway Pressure Release Ventilation, Bilevel Continuous Positive Airway Pressure, Biphasic Continuous Positive Airway Pressure, Mechanical Ventilation, Ventilator-Induced Lung Injury, Spontaneous Breathing
- Medical subject headings
- Respiratory Distress Syndrome, Ventilator-Induced Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
spontaneous breathing activity during APRVProcedure or surgery
Allowing spontaneous breathing activity with APRV throughout the first 48 hours.
No spontaneous breathing activityProcedure or surgery
No spontaneous breathing activity will be allowed with pressure controlled ventilation throughout the first 48 hours.
| Study group | Role | What they receive |
|---|---|---|
| Spontaneous Breathing Group | Experimental | 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. Receives: Procedure: spontaneous breathing activity during APRV |
| Controlled Mechanical Ventilation Group | Experimental | 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. Receives: Procedure: No spontaneous breathing activity |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: All-cause mortality at D28 will be defined as number of patients who deceased at day 28.
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.
Measured: Number of Ventilator Free Days will be measured until day 28.
Secondary outcomes (4)
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.
Measured: All-cause mortality at D90 will be defined as number of patients who deceased at day 90.
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.
Measured: Number of Vasoactive Drug Free Days will be measured until D28.
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.
Measured: Number of Renal Support Free Days will be measured until study day 28.
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2020
- Study start8 Feb 2020
- Primary completionFeb 2024 (estimated)
- Study completionJul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Respiratory Distress Syndrome, AdultStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 840 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bonn
- Sponsor type
- University, hospital or other
- Collaborators
- European Society of Anaesthesiology
- Responsible party
- Principal investigator, Christian Putensen, University Hospital, Bonn
- Investigators
- Christian Putensen, M.D., PhD., Principal investigator, University Hospital, Bonn
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04228471
- Sponsor's protocol ID
- UKB_PReSPON
- Acronym
- PReSPON
- Status last verified
- Feb 2021
- First submitted
- 19 Dec 2019
- Last updated
- 9 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early PReserved SPONtaneous Breathing Activity in Mechanically Ventilated Patients With Acute Respiratory Distress Syndrome - The PReSPON Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04228471
- Acronym / sponsor ID
- PReSPON / UKB_PReSPON
- 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
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 840 participants (estimated)
- Lead sponsor
- University Hospital, BonnUniversity, hospital or other
- Collaborators
- European Society of Anaesthesiology
- Study start
- 8 Feb 2020 (actual)
- Primary completion
- Feb 2024 (estimated)
- Study completion
- Jul 2024 (estimated)
- First posted
- 14 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Spontaneous Breathing Group | Experimental | Procedure: spontaneous breathing activity during APRVSpontaneous 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. |
| Controlled Mechanical Ventilation Group | Experimental | Procedure: No spontaneous breathing activityPressure 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Moderate to severe ARDS for ≤ 48 hours according to the Berlin definition will be defined by acute onset of:
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| spontaneous breathing activity during APRVAllowing spontaneous breathing activity with APRV throughout the first 48 hours. | Procedure or surgery | Spontaneous Breathing Group |
| No spontaneous breathing activityNo spontaneous breathing activity will be allowed with pressure controlled ventilation throughout the first 48 hours. | Procedure or surgery | Controlled Mechanical Ventilation Group |
Primary outcome
All-cause mortality at study day 28 (D28)
Time frame: All-cause mortality at D28 will be defined as number of patients who deceased at day 28.
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)
Time frame: Number of Ventilator Free Days will be measured until day 28.
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.
4 secondary outcomes
All-Cause Mortality Rate at study day 90 (D90)
Time frame: All-cause mortality at D90 will be defined as number of patients who deceased at day 90.
Number of Vasoactive Drug Free Days until study day 28 (D28)
Time frame: Number of Vasoactive Drug Free Days will be measured until D28.
Number of Renal Support Free Days until study day 28 (D28)
Time frame: Number of Renal Support Free Days will be measured until study day 28.
Sequential Organ Failure Assessment (SOFA)
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christian Putensen, M.D., PhD. principal investigator
University Hospital, Bonn
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing spontaneous breathing activity during APRV and No spontaneous breathing activity in people with Respiratory Distress Syndrome, Adult, run by University Hospital, Bonn at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Christian Putensen, M.D., PhD. (+49 228 287 ext. 14119, Christian.Putensen@ukbonn.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All-cause mortality at study day 28 (D28) (time frame: All-cause mortality at D28 will be defined as number of patients who deceased at day 28.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2021.