Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Extracorporeal Carbon Dioxide Removal, ECCO2R, Noninvasive Ventilation, NIV, Acute Hypercapnic Respiratory Failure, Respiratory Acidosis, COPD Exacerbation, Do-Not-Intubate Order
Brief summary
This study will evaluate whether adding extracorporeal carbon dioxide removal (ECCO2R) to noninvasive ventilation can improve breathing in adults hospitalized with a severe worsening of chronic obstructive pulmonary disease (COPD). Participants will have high carbon dioxide levels and increased acidity in their blood despite treatment with noninvasive ventilation and will not be eligible for invasive mechanical ventilation through a breathing tube. A total of 14 participants will be assigned by chance to receive either noninvasive ventilation alone or noninvasive ventilation together with ECCO2R. ECCO2R removes carbon dioxide directly from the blood through a catheter placed in a large vein. The main aim is to determine whether adding ECCO2R reduces the breathing rate within 4 hours. The study will also assess blood carbon dioxide and acidity, duration of noninvasive ventilation, length of hospital stay, survival, and complications related to ECCO2R.
Detailed description
Acute exacerbations of chronic obstructive pulmonary disease (COPD) may cause severe hypercapnic respiratory failure. Noninvasive ventilation (NIV) is the standard initial respiratory support, but some patients have persistent respiratory acidosis despite NIV. Treatment options are particularly limited when invasive mechanical ventilation is not considered appropriate or is declined by the patient. Extracorporeal carbon dioxide removal (ECCO2R) uses a low-flow extracorporeal circuit to remove carbon dioxide directly from the blood. When used together with NIV, ECCO2R may reduce the ventilatory demand and work of breathing, improve respiratory acidosis, and facilitate earlier withdrawal of NIV. This single-center, open-label, randomized proof-of-concept trial will compare NIV plus ECCO2R with NIV alone in patients with an acute exacerbation of COPD and persistent hypercapnic respiratory acidosis after 4 hours of NIV. The study is intended to provide preliminary evidence regarding the physiological effects, clinical feasibility, and safety of adding ECCO2R to standard NIV in this highly selected population. The findings may inform the design of larger clinical trials.
Interventions
Low-flow extracorporeal carbon dioxide removal will be provided using the Prismalung+ membrane connected to the PrisMax 2 system. Treatment will be initiated within 12 hours after randomization through a 13- to 14-Fr double-lumen venous catheter. The initial sweep gas flow will be 10 L/min, and blood flow will be set as high as tolerated by the system, with a target of approximately 450 mL/min. Treatment settings will be adjusted according to carbon dioxide removal and arterial pH.
DEVICENoninvasive Ventilation
Noninvasive ventilation will be delivered according to current clinical guidelines and usual clinical practice. Ventilator settings and duration of treatment will be adjusted by the treating clinical team according to the participant's respiratory status and clinical response.
Sponsors
Hospital del Mar Research Institute (IMIM)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants are randomly assigned in a 1:1 ratio to receive either noninvasive ventilation plus extracorporeal carbon dioxide removal or noninvasive ventilation alone.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older. * Confirmed diagnosis of chronic obstructive pulmonary disease (COPD). * Acute exacerbation of COPD, defined as increased dyspnea, cough, and/or sputum production. * Acute hypercapnic respiratory failure requiring noninvasive ventilation, with arterial pH \<7.30 and PaCO2 \>50 mmHg. * Not eligible for endotracheal intubation because of a medical decision or the participant's prior decision. * Persistent respiratory acidosis, defined as arterial pH \<7.30 with PaCO2 \>45 mmHg, after 4 hours of noninvasive ventilation.
Exclusion criteria
* Contraindication to extracorporeal carbon dioxide removal due to a coagulation disorder. * Inability to establish adequate vascular access.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Respiratory Rate From Baseline to 4 Hours | Baseline and 4 hours after initiation of the assigned treatment | Change in respiratory rate, measured in breaths per minute, from the study baseline to 4 hours after initiation of ECCO2R in the experimental arm or the corresponding study time point in the control arm. A negative value indicates a reduction in respiratory rate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Arterial Carbon Dioxide Pressure | Baseline and 4 hours after initiation of the assigned treatment | Change in arterial partial pressure of carbon dioxide (PaCO2), measured in mmHg, from baseline to 4 hours after initiation of the assigned treatment. |
| Change in Arterial pH | Baseline and 4 hours after initiation of the assigned treatment | Change in arterial blood pH from baseline to 4 hours after initiation of the assigned treatment. |
| Duration of Noninvasive Ventilation | From initiation of noninvasive ventilation until its permanent discontinuation, assessed through hospital discharge or death | Total duration of noninvasive ventilation, measured in hours, from initiation until permanent discontinuation during the index hospitalization. |
| Hospital Length of Stay | From hospital admission through hospital discharge or death, anticipated up to 90 days | Number of days from hospital admission to hospital discharge or in-hospital death. |
| In-Hospital Mortality | From randomization through hospital discharge, anticipated up to 90 days | All-cause mortality occurring during the index hospitalization. |
| Incidence of ECCO2R-Related Adverse Events | From initiation of ECCO2R through hospital discharge or death, anticipated up to 90 days | Number and proportion of participants experiencing one or more adverse events considered related to ECCO2R, including bleeding, thrombocytopenia, vascular catheter complications, hemolysis, circuit clotting, air entry, reduced blood flow, or other mechanical system failures. |
Countries
Spain
Contacts
CONTACTFrancisco José Parrilla Gómez, MD, PhD
CONTACTAndrea Castellvi-Font, MD, PhD
PRINCIPAL_INVESTIGATORFrancisco José Parrilla Gómez, MD, PhD
Hospital del Mar
Outcome results
None listed