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

NCT ID: NCT04228471

Last Updated: 2021-02-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 840 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-08
• Study Completion Date: 2024-07-31

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.

Conditions

Respiratory Distress Syndrome, Adult

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Spontaneous Breathing Group

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.

Group Type: EXPERIMENTAL

spontaneous breathing activity during APRV

Intervention Type: PROCEDURE

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

Controlled Mechanical Ventilation Group

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.

Group Type: EXPERIMENTAL

No spontaneous breathing activity

Intervention Type: PROCEDURE

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

Interventions

spontaneous breathing activity during APRV

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

Intervention Type: PROCEDURE

No spontaneous breathing activity

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

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Society of Anaesthesiology

OTHER

Sponsor Role: collaborator

University Hospital, Bonn

OTHER

Sponsor Role: lead

Responsible Party

Christian Putensen

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christian Putensen, M.D., PhD.

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Bonn

Locations

University Hospital Bonn, Department of Anesthesiology and Critical Care Medicine

Bonn, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Christian Putensen, M.D., PhD.

Role: CONTACT

Christian.Putensen@ukbonn.de

+49 228 287 ext. 14119

Stefan Muenster, M.D.

Role: CONTACT

Stefan.Muenster@ukbonn.de

+49 228 287 ext. 14119

Facility Contacts

Christian Putensen, MD, PhD

Role: primary

christian.putensen@ukbonn.de

+4922828714119

Stefan Muenster, MD

Role: backup

stefan.muenster@ukbonn.de

+4922828714119

Other Identifiers

UKB_PReSPON

Identifier Type: -

Identifier Source: org_study_id