Hypercapnia, Respiratory Insufficiency
Conditions
Keywords
Hypercapnia, noninvasive ventilation, acute respiratory failure, endotracheal intubation, invasive mechanical ventilation
Brief summary
The study´s intention is to evaluate the feasibility, safety and effectiveness of a pump driven extracorporeal device for removal of carbon dioxide from the blood in oder to avoid intubation and invasive mechanical ventilation in patients with acute respiratory failure retaining carbon dioxide due to the failure of their ventilatory muscle pump and not responding to prior non-invasive mask ventilation.
Detailed description
The study´s intention is to evaluate the feasibility, safety and effectiveness of a pump driven extracorporeal device for removal of carbon dioxide from the blood in oder to avoid intubation and invasive mechanical ventilation in patients with acute respiratory failure retaining carbon dioxide due to the failure of their ventilatory muscle pump and not responding to prior non-invasive mask ventilation. Since intubation with subsequent (prolonged) invasive mechanical ventilation is associated with considerable side effects this new strategy has the potential to improve overall clinical outcome in this selected patient group.
Interventions
DEVICEvv-ECCO2R (Novalung GmbH, Germany)
Treatment with the extracorporeal lung assist (ECLA) The ECLA is a pump driven (centrifugal pump) venovenous circuit, which removes carbon dioxide from the patients blood by means of a membrane through which the patients blood runs on the one side of the membrane and sweep gas on the other side removing the patient´s carbon dioxide. Blood flow range from 0.5 to 4.5 l/min and sweep gas flow between 1 and 10 l/min. At blood flows of 2 l/min and higher the device also oxygenates the patients blood. The diameter and length of cannulas and the sites of venous insertions are left to the decision of the treating physician. Cannulas are inserted in seldinger technique under sterile conditions. Function and patency of the extracorporeal circuit requires mild therapeutic anticoagulation.
Sponsors
Universitätsklinikum Hamburg-Eppendorf
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* acute or acute-on-chronic hypercapnic respiratory insufficiency (pH ≤ 7,35, PaCO2 \> 45 mmHg) * failure of noninvasive ventilation * fulfilling criteria for endotracheal intubation
Exclusion criteria
* under 18 years of age * prior inclusion in other interventional study * pregnancy * heparin allergy or heparin-induced thrombocytopenia type 2 * on home non-invasive ventilator * Do not resuscitate order or moribund condition * life expectancy less than 6 months * no informed consent available
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Need for Intubation for Invasive Mechanical Ventilation | 21 days | The number of patients in the ECLA-group who had to be intubated and mechanically ventilated under the given criteria for inclusion and exclusion is collected. Since every patient in the matched control group was intubated, the comparison of the groups shows whether the use of a pump-driven venovenous extracorporeal lung assist can reduce the frequency of intubation and mechanical ventilation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of Non-invasive Ventilation | 90 days | The duration of non-invasive ventilation up to day 90 is used to evaluate the respiratory outcomes of ECLA versus invasive mechanical ventilation. |
| Complication Rates | 90 days | Major complication associated with the pump driven extracorporeal lung assist device or with non-invasive or invasive mechanical ventilation or any associated treatments during the observational period |
| Length of Invasive Mechanical Ventilation if Intubated | 90 days | Describes the length of invasive mechanical ventilation in days, in case intubation and mechanical ventilation became necessary |
| Length of Stay in ICU | 90 days | Describes the length of stay in ICU |
| Mortality | 90 days | Comparison of 90-day mortality between the study arms. Seven patients died in each of the two arms after 90 days, so the stated values are correct. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ECLA Group Treatment with a pump driven, venovenous extracorporeal lung assist
vv-ECCO2R (Novalung GmbH, Germany): Treatment with the extracorporeal lung assist (ECLA) The ECLA is a pump driven (centrifugal pump) venovenous circuit, which removes carbon dioxide from the patients blood by means of a membrane through which the patients blood runs on the one side of the membrane and sweep gas on the other side removing the patient´s carbon dioxide. Blood flow range from 0.5 to 4.5 l/min and sweep gas flow between 1 and 10 l/min. At blood flows of 2 l/min and higher the device also oxygenates the patients blood. The diameter and length of cannulas and the sites of venous insertions are left to the decision of the treating physician. Cannulas are inserted in seldinger technique under sterile conditions. Function and patency of the extracorporeal circuit requires mild therapeutic anticoagulation. | 25 |
| Control Group Control patients were identified and their data retrospectively collected from a large patient database at the principal study centre. The control patients had also been admitted to Intensive Care Unit with hypercapnic ventilatory failure and subsequently failed non-invasive ventilation (NIV) treatment followed by intubation and invasive mechanical ventilation. Matching criteria for the historical controls were acute diagnosis leading to hypercapnic respiratory failure, age (±10), SAPS-II score (±6) on ICU admission and pH (±0.06) at the time of NIV failure. | 25 |
| Total | 50 |
Baseline characteristics
| Characteristic | ECLA Group | Control Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 15 Participants | 15 Participants | 30 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 10 Participants | 20 Participants |
| Age, Continuous | 67 years | 68 years | 67 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 25 Participants | 25 Participants | 50 Participants |
| Region of Enrollment Austria | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Germany | 21 participants | 25 participants | 46 participants |
| Region of Enrollment Netherlands | 2 participants | 0 participants | 2 participants |
| Sex: Female, Male Female | 13 Participants | 12 Participants | 25 Participants |
| Sex: Female, Male Male | 12 Participants | 13 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 25 | 7 / 25 |
| other Total, other adverse events | 4 / 25 | 8 / 25 |
| serious Total, serious adverse events | 11 / 25 | 2 / 25 |
Outcome results
Primary
Number of Patients With Need for Intubation for Invasive Mechanical Ventilation
The number of patients in the ECLA-group who had to be intubated and mechanically ventilated under the given criteria for inclusion and exclusion is collected. Since every patient in the matched control group was intubated, the comparison of the groups shows whether the use of a pump-driven venovenous extracorporeal lung assist can reduce the frequency of intubation and mechanical ventilation.
Time frame: 21 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ECLA-group | Number of Patients With Need for Intubation for Invasive Mechanical Ventilation | 11 Participants |
| Control Group | Number of Patients With Need for Intubation for Invasive Mechanical Ventilation | 25 Participants |
Secondary
Complication Rates
Major complication associated with the pump driven extracorporeal lung assist device or with non-invasive or invasive mechanical ventilation or any associated treatments during the observational period
Time frame: 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ECLA-group | Complication Rates | 11 Participants |
| Control Group | Complication Rates | 2 Participants |
Secondary
Length of Invasive Mechanical Ventilation if Intubated
Describes the length of invasive mechanical ventilation in days, in case intubation and mechanical ventilation became necessary
Time frame: 90 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| ECLA-group | Length of Invasive Mechanical Ventilation if Intubated | 8.3 days |
| Control Group | Length of Invasive Mechanical Ventilation if Intubated | 13.7 days |
Secondary
Length of Non-invasive Ventilation
The duration of non-invasive ventilation up to day 90 is used to evaluate the respiratory outcomes of ECLA versus invasive mechanical ventilation.
Time frame: 90 days
Population: As the control group receives 100% invasive mechanical ventilation by definition, this group is not analysed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| ECLA-group | Length of Non-invasive Ventilation | 4.6 days |
Secondary
Length of Stay in ICU
Describes the length of stay in ICU
Time frame: 90 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| ECLA-group | Length of Stay in ICU | 28.9 days |
| Control Group | Length of Stay in ICU | 24.0 days |
Secondary
Mortality
Comparison of 90-day mortality between the study arms. Seven patients died in each of the two arms after 90 days, so the stated values are correct.
Time frame: 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ECLA-group | Mortality | 7 Participants |
| Control Group | Mortality | 7 Participants |