IMV to Accelerate Recovery of Lung Function in Veno-venous Extracorporeal Membrane Oxygenation; Lung Rest Or Moderate Mechanical Ventilation in ECMO

NCT ID: NCT06006676

Last Updated: 2024-02-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-22
• Study Completion Date: 2026-03-01

Brief Summary

Feasibility trial to inform a future multicentre randomized control trial. The investigators aim to evaluate the feasibility of a trial of near apnoeic ventilation (two breaths per minute) compared with standard ventilation (respiratory rate between 10 and 30 breaths) for patients with acute respiratory distress syndrome (ARDS) supported with veno-venous extracorporeal membrane oxygenation (V-V ECMO). Additionally, when a patient is determined as ready to wean from ECMO the investigators will explore the feasibility of two ECMO weaning strategies and explore the physiological effects on respiratory effort and gas exchange.

Detailed Description

Background

Acute respiratory distress syndrome (ARDS) is a common clinical syndrome characterised by life threatening respiratory failure requiring mechanical ventilation. Although lifesaving, mechanical ventilation can cause further injury to the lungs, known as ventilator-induced lung injury (VILI). Strategies to mitigate VILI in ARDS have proven to improve patient outcomes. ARDS patients that have severe lung failure, despite mechanical ventilation, often require veno-venous extracorporeal membrane oxygenation (ECMO). ECMO uses an artificial membrane lung to take over gas exchange. This allows reduction in injurious ventilator settings thereby also reducing VILI.

While the indications for ECMO initiation are standardised in the UK and ECMO utilisation is increasing,there remains uncertainty as to the best approach to mechanical ventilation whilst patients are receiving ECMO and what strategies are maximally attenuating VILI during its use. Importantly it is known that despite the reduction in ventilatory pressures and volumes facilitated by ECMO, these sickest and most fragile lungs continue to be susceptible to VILI. A reduction in respiratory rate (RR) to near apnoeic ventilation (2 breaths per minute) seems to be associated with the greatest physiological reduction in VILI components, whilst maintaining important physiological mechanisms such as surfactant production which rely on some lung inflation. Employing a near apnoeic ventilation strategy may be associated with faster resolution of ARDS resulting in reduced duration of ECMO, ventilation and ICU stay, and healthcare costs.

Rationale

Interventions which mitigate VILI lead to less lung inflammation/oedema and better outcomes in ARDS patients. However, the recent REST trial of extracorporeal carbon dioxide removal showed that the resultant modest reduction in volume and pressure had no clinical effect. Hence, a modest reduction in ventilation may not be as effective as an almost complete absence (near apnoeic) of ventilation. The latter can only be achieved alongside ECMO support. Reductions in respiratory rate to near apnoeic ventilation have multiple effects on VILI, including:

1. Modulation of disease activity through reduced opening and closing of lung units (atelectrauma);

2. Reductions in frequency of applied driving pressure and overall intensity of minute ventilation (barotrauma)

3. Prevention of overdistension of the aerated lung (volutrauma)

4. Attenuation of circulating markers of lung injury and inflammation ('biotrauma')

5. Reduced development of aberrant fibrosis within the lung [9]. Patients on ECMO are prone to pulmonary fibrosis, for which VILI is known to be major contributor

Multinational surveys of mechanical ventilation during ECMO support show that 45.7% of centres used a moderate respiratory rate (10-20 breaths per minute) delivered with ~10-15 cmH2O PEEP and 10-15 cmH2O driving pressure. Evidence shows a 3% increase in the hazard of death for every 1 cmH2O increase in ventilator driving pressure during ECMO support. Taken together, international experience and trend show that ventilator mechanical power (a measure of the energy transmitted to the lung) is a major determinant of VILI and is only modestly decreased by the currently employed moderate ventilation strategies which mainly reduce the driving pressure applied per breath. Mechanical power is, however, significantly reduced by lower respiratory rates. Near apnoeic ventilation during ECMO is clinically feasible with gas exchange and oxygen delivery being maintained by ECMO.

The ROMEO trial

The investigators have conducted a detailed search of PubMed, Ovid, Cochrane databases, Google Scholar and the WHO International Clinical Trials Registry Platform. To-date, no large prospective studies have or are addressing the use of near apnoeic ventilation during ECMO. Consequently, a multicentre randomised open label study of near apnoea ventilation versus standard of care is planned. This future multicentre trial will be powered for patient centred outcomes (e.g., time to ECMO decannulation and mortality) together with a trial cost utility analysis at 12 months.

To demonstrate the feasibility of our trial design, we will conduct a 50 patient feasibility study at Guy's and St Thomas' NHS Foundation Trust. This will evaluate the feasibility of the intervention (ability to recruit; ability to deliver the ventilator strategy; ability to deliver the ECMO weaning strategies), the physiological changes induced by near apnoea ventilation together with the impact on plasma and broncho-alveolar lavage biomarkers and collect exploratory data on clinical outcomes.

As there is a paucity of evidence regarding predictors of ECMO weaning success, we will evaluate comprehensive physiological data obtained during each weaning trial attempt to evaluate the patient-ventilator-membrane lung interactions.

Conditions

ARDS

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Near Apnoeic Ventilation

Near Apnoeic ventilation (with a respiratory rate of 2 breaths per minute, plateau pressure of 30cmH20 and PEEP set according to the mean airway pressure being delivered during mechanical ventilation prior to randomisation) for a 72 hour period following randomisation

Group Type: EXPERIMENTAL

Near Apnoeic ventilation

Intervention Type: OTHER

Near Apnoeic ventilation (with a respiratory rate of 2 breaths per minute, plateau pressure of 30cmH20 and PEEP set according to the mean airway pressure being delivered during mechanical ventilation prior to randomisation) for a 72 hour period following randomisation

Crossover standardised ECMO weaning trials

Intervention Type: OTHER

When all patients are eligible for a trial of ECMO weaning, they will have standardised ECMO weaning trials lasting up to 1 hour with 0 sweep gas flow. 1) "One-stage weaning"- sweep gas flow rate sequentially decreased to zero 2) "Two-stage weaning"- fraction of oxygen of sweep gas flow decreased to 0.21 sequentially. Then the sweep gas flow rate decreased to 0 sequentially

Standard Care

Standard care for patient on ECMO as per consultant with respiratory rate of 15-30, PEEP of 10cmH20 or more and Plateau pressure of 25cmH20 or less for a 72 hour period following randomisation

Group Type: ACTIVE_COMPARATOR

Crossover standardised ECMO weaning trials

Intervention Type: OTHER

When all patients are eligible for a trial of ECMO weaning, they will have standardised ECMO weaning trials lasting up to 1 hour with 0 sweep gas flow. 1) "One-stage weaning"- sweep gas flow rate sequentially decreased to zero 2) "Two-stage weaning"- fraction of oxygen of sweep gas flow decreased to 0.21 sequentially. Then the sweep gas flow rate decreased to 0 sequentially

Interventions

Near Apnoeic ventilation

Near Apnoeic ventilation (with a respiratory rate of 2 breaths per minute, plateau pressure of 30cmH20 and PEEP set according to the mean airway pressure being delivered during mechanical ventilation prior to randomisation) for a 72 hour period following randomisation

Intervention Type: OTHER

Crossover standardised ECMO weaning trials

When all patients are eligible for a trial of ECMO weaning, they will have standardised ECMO weaning trials lasting up to 1 hour with 0 sweep gas flow. 1) "One-stage weaning"- sweep gas flow rate sequentially decreased to zero 2) "Two-stage weaning"- fraction of oxygen of sweep gas flow decreased to 0.21 sequentially. Then the sweep gas flow rate decreased to 0 sequentially

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Adult patients aged 18 years or older on the date of screening
• Acute and potentially reversible cause of ARDS
• Receiving invasive mechanical ventilation
• Requiring ECMO for severe ARDS
• Tidal volume ≥ 2.5ml/kg predicted body weight

Exclusion Criteria

Patients who meet the one or more of the following will be excluded from the trial.

• Declined consent
• >12 hours following ECMO initiation
• Patient likely to die or for withdrawal of life sustaining therapies within 24 hours
• Use of V-A ECMO or hybrid ECMO modes
• Current pregnancy

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

Sponsors

Guy's and St Thomas' NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Luigi Camporota, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Guy's and St Thomas' NHS Foundation Trust

Locations

Guys & St. Thomas' NHS Foundation Trust

London, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Luigi Camporota, MD, PhD

Role: CONTACT

luigi.camporota@gstt.nhs.uk

02071883036

Gill Radcliffe

Role: CONTACT

gill.radcliffe@gstt.nhs.uk

02071888070

Facility Contacts

Luigi Camporota, MD

Role: primary

luigi.camporota@gstt.nhs.uk

Gill Radcliffe, PhD

Role: backup

gill.radcliffe@gstt.nhs.uk

Other Identifiers

256932

Identifier Type: -

Identifier Source: org_study_id