Extracorporeal Lung Assist Device in Acute Lung Impairment

NCT ID: NCT02550600

Last Updated: 2015-09-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2017-12-31

Brief Summary

The purpose of this study is to compare the effect of interventional Lung Assist iLA activve to standard therapy in mechanically ventilated patients with severe acute lung impairment. Hypothesis: iLA(active) reduces the incidence of an increase in SOFA-Score of ≥3 points (or death) within 28 days compared to standard treatment.

Detailed Description

Background:

Mechanical ventilation in patients with acute lung impairment further injures the lungs by inspiration forces and inflammatory response. Large efforts have been invested in reducing ventilator-associated lung damage by lower tidal volumes. However, benefits are limited by potential harms of permissive hypercapnia.

Therefore, extracorporeal membrane oxygenation (ECMO) and CO2-removal have been studied for more than 40 years. However, ECMO remained restricted to few specialized centres capable to provide extensive resources. Transfer of patients implicates loss of time and risks of transportation. Therefore, less invasive devices have been developed, including "pump-less "extracorporeal lung assist" (pECLA) and pump-driven ECLA (e.g. iLA activve). Despite pilot trials supporting feasibility, safety and efficient oxygenation and decarboxylation by pump-driven ECLA, there are no randomized controlled trials (RCT) proving a benefit regarding long-term endpoints.

Objectives:

Therefore, the aim of this multicentre RCT is to compare the outcome of 150 patients with early (after ≤96h of mechanical ventilation) acute lung impairment treated by pump-driven ECLA with iLA activve with a blood flow of at least 1L/min vs. 150 controls with standard intensive care including low tidal volume ventilation.

Main inclusion and exclusion criteria:

While most trials on ECMO and (p)ECLA included patients in a rescue scenario with severe and persisting ARDS, earlier inclusion also implicates modified inclusion criteria: A cumulative Murray score of ≥6 points without radiological points is the most important inclusion criterion. At least four points must result from pO2/FiO2 (mandatory pO2/FiO2<300mmHg) and PEEP criteria of the Murray score. In order to provide sufficient time for conservative attempts to optimize ventilation, inclusion criteria can be fulfilled for a maximum of 48h before inclusion as long as the patient can be included within a maximum of 96h of mechanical ventilation.

Primary efficacy endpoint:

Incidence of an increase in SOFA-Score ≥3 points or death within 28 days.

Statistical analyses:

Generalized linear mixed model (logit link function) will be used to compare the primary efficacy endpoint, the proportion of patients with an increase in SOFA of ≥3 points or death within 28d, between the two groups. In this analysis the random factor variable study centre and anticoagulation therapy will be considered as adjustment variables. The test of group effect estimated by the multivariable mixed logistic model will be conducted at a two-sided 0.05 level of significance.

The primary efficacy analysis will be based on the intention-to-treat population. Missing values of SOFA score will be replaced by last-value carry forward approach.

Survival status of lost to follow-up patients will be replaced conservatively: missing survival status will be replaced by attribute "death" for patients in the verum arm and replaced by attribute "alive" for patients in the standard treatment arm.

A supportive complete case and per-protocol analysis will be conducted for purpose of sensitivity analysis of the primary endpoint. Further sensitivity analyses will be provided to evaluate robustness of results in regard to unexpected circumstances (e.g. impact of 'cross-over' patients who are not treated as randomized but are required to be analyzed as randomized (ITT-principle)). Secondary endpoints will be analyzed in an exploratory manner.

Chi-Square test or Fisher-exact test will be used to compare categorical data. For comparisons of continuous data between groups non-parametric tests (Kruskal-Wallis test, Mann-Whitney-U test) will be performed. 95% confidence intervals will be calculated for relevant measurements. SAS software (version 4.9 or future follow-up version).

Conditions

Acute Respiratory Distress Syndrome

Study Design

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

Study Groups

Intervention group

Intervention: iLA activve treatment. iLA activve treatment also requires anticoagulation with un-fractionized heparin and pre-defined PTT-goals (45s-60s depending on blood flow).

Group Type: EXPERIMENTAL

iLA activve treatment

Intervention Type: PROCEDURE

iLA activve is aimed at efficient extracorporeal membrane oxygenation with an initial blood flow of ≥2L/min. The length of therapy is at the discretion of the treating physician.

Treating physicians are recommended to use a pre-specified algorithm to optimize the extracorporeal lung assist (choice of cannulas and oxygenator, titration of blood flow and sweep gas flow). Primary/mandatory goals are pO2≥65mmHg, P_peak ≤30cm H2O, TV ≤6ml/kg PBW and pH ≥7.25. Secondary suggested goals are setting the PEEP level within the limits suggested by the ARDSnet low and high PEEP strategy, 35mmHg ≤ pCO2 ≤45mmHg, Delta-pressure (= P_peak - PEEP) ≤15 cm H2O and P_peak ≤25 cm H2O.

iLA activve treatment also requires anticoagulation with un-fractionized heparin (PTT-goal 45s-60s depending on blood flow).

Control group

Controls: standard care according to good clinical practice and recent guidelines; no extracorporeal lung assist.

For ethical reasons patients of the control group can be treated with iLA activve after fulfilling the primary endpoint criterium of an increase in SOFA ≥3 points. These cross-over patients will be analyzed as controls ("intention to treat").

Group Type: ACTIVE_COMPARATOR

Control group

Intervention Type: PROCEDURE

The controls will be treated according to the recent guideline of the German Sepsis Society and the German Interdisciplinary Association of Intensive Care and Emergency Medicine and good clinical practice including lung-protective ventilation with low tidal volume (LTV), moderate hypercapnia, PEEP according to ARDSnet, adjunctive measures (e.g. prone positioning; neuromuscular blockers as appropriate) and treatment of the underlying disease as applied in the experimental group.

There will be no sham treatment of iLA activve.in the controls. All adjunctive measures (e.g. prone positioning; neuromuscular blockers as appropriate) are also available for the intervention group.

Interventions

iLA activve treatment

iLA activve is aimed at efficient extracorporeal membrane oxygenation with an initial blood flow of ≥2L/min. The length of therapy is at the discretion of the treating physician.

Treating physicians are recommended to use a pre-specified algorithm to optimize the extracorporeal lung assist (choice of cannulas and oxygenator, titration of blood flow and sweep gas flow). Primary/mandatory goals are pO2≥65mmHg, P_peak ≤30cm H2O, TV ≤6ml/kg PBW and pH ≥7.25. Secondary suggested goals are setting the PEEP level within the limits suggested by the ARDSnet low and high PEEP strategy, 35mmHg ≤ pCO2 ≤45mmHg, Delta-pressure (= P_peak - PEEP) ≤15 cm H2O and P_peak ≤25 cm H2O.

iLA activve treatment also requires anticoagulation with un-fractionized heparin (PTT-goal 45s-60s depending on blood flow).

Intervention Type: PROCEDURE

Control group

The controls will be treated according to the recent guideline of the German Sepsis Society and the German Interdisciplinary Association of Intensive Care and Emergency Medicine and good clinical practice including lung-protective ventilation with low tidal volume (LTV), moderate hypercapnia, PEEP according to ARDSnet, adjunctive measures (e.g. prone positioning; neuromuscular blockers as appropriate) and treatment of the underlying disease as applied in the experimental group.

There will be no sham treatment of iLA activve.in the controls. All adjunctive measures (e.g. prone positioning; neuromuscular blockers as appropriate) are also available for the intervention group.

Intervention Type: PROCEDURE

Other Intervention Names

ECMO; Extra-corporeal lung assist

Eligibility Criteria

Inclusion Criteria

• Potentially reversible lung failure AND
• Cumulative Murray score ≥6 points without radiological points for a maximum of 48h AND
• Cumulative Murray score ≥4 points for pO2/FiO and PEEP AND
• Cumulative Murray score ≥1 point for pO2/FiO
• Mechanical ventilation for ≤96h AND
• Age ≥ 18 years.

Exclusion Criteria

• SOFA-Score >20
• Life expectancy <24h
• mechanical ventilation >96h
• Heparin-induced thrombopenia
• Intracranial bleeding

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

Sponsors

Novalung GmbH, Heilbronn, Germany

UNKNOWN

Sponsor Role: collaborator

Studiensekretariat Intensivmedizin; II. Medizinische Klinik; Klinikum rechts der Isar; Munich

UNKNOWN

Sponsor Role: collaborator

Technical University of Munich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wolfgang Huber, MD

Role: PRINCIPAL_INVESTIGATOR

II. Medizinische Klinik; Klinikum rechts der Isar; Ismaningerstrasse 22; D-81675 München; Germany

Locations

Medical University of Vienna/General Hospital of Vienna

Vienna, , Austria

Klinik für Intensivmedizin; Universitätsklinikum Hamburg-Eppendorf (UKE)

Hamburg, , Germany

Abteilung für Intensivmedizin; Krankenhaus Barmherzige Brüder; München

Munich, , Germany

I. Medizinische Klinik; Klinikum rechts der Isar; Technische Universität München

Munich, , Germany

II. Medizinische Klinik; Klinikum rechts der Isar; Technische Universität München

München, , Germany

Klinik für Anästhesiologie; Klinikum rechts der Isar; Technische Universität München

München, , Germany

Department of Anaesthesiology and Intensive Therapy; University of Szeged

Szeged, , Hungary

St. Bartholomew's & London Chest Hospitals

London, , United Kingdom

Countries

Austria; Germany; Hungary; United Kingdom

Central Contacts

Wolfgang Huber, MD

Role: CONTACT

Wolfgang.Huber@lrz.tum.de

++49-89-4140-5214

Regina Sommer, Study Nurse

Role: CONTACT

Regina.Sommer@lrz.tum.de

++49-89-4140-5478

Facility Contacts

Thomas Staudinger, MD

Role: primary

thomas.staudinger@meduniwien.ac.at

++43-01-40400-44920

Stefan Kluge, MD

Role: primary

s.kluge@uke.de

++49-40-7410-57010

Bernd Saugel, MD

Role: backup

b.saugel@uke.de

++49-40-7410-52415

Franz Brettner, MD

Role: primary

franz.brettner@barmherzige-muenchen.de

++49-89-1797-2218

Petra Hoppmann, MD

Role: primary

Petra.Hoppmann@mri.tum.de

++49-89-4140-9670

Juliane Jaitner, MD

Role: backup

Juliane.Jaitner@gmx.de

++49-89-4140-2367

Wolfgang Huber, MD

Role: primary

Wolfgang.Huber@lrz.tum.de

++49-89-4140-5214

Regina Sommer, Study Nurse

Role: backup

Regina.Sommer@lrz.tum.de

++49-89-4140-5478

Ralf Bogdanski, MD

Role: primary

r.bogdanski@lrz.tu-muenchen.de

++49-89-4140-5472

Zsolt Molnar, MD

Role: primary

z_molnar@hotmail.com

Eva Zollei, MD

Role: backup

Benjamin O´Brien, MD; PhD

Role: primary

Sibtain Anwar, MD

Role: backup

Other Identifiers

EXO_1

Identifier Type: -

Identifier Source: org_study_id