The Effects of Enoximone in Acute Exacerbation COPD

Study Overview
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Brief Summary
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Introduction: The pharmacodynamic properties of enoximone could be beneficial for patients with an Acute Exacerbation COPD (AE-COPD). This research will focus on patients suffering of a severe AE-COPD and the bronchodilatory and inotropic effects of lower doses of enoximone. The main objective of the pilot study is to investigate if there is a bronchodilatory effect of enoximone in patients with AE-COPD. Secondary objective is to investigate a dose responsiveness in a range between 0.5 and 1.5 mg/kg enoximone. Methods: The study design is a prospective interventional non-randomized clinical series study involving patients admitted and intubated at the Intensive Care Unit (ICU) with an AE-COPD. Patients will receive three times a dose of 0.5 mg/kg enoximone with a one-hour-interval. The primary objective is a reduction in auto-positive end-expiratory pressure (PEEP) after enoximone compared to baseline. A dose-titration will test for dose dependency. Secondary objectives are a reduction in ventilator pressures, a reduction in pulmonary artery pressures and an increase in cardiac output.

Detailed Description
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Ventilator will be set during the study period at Volume Controle, 6 ml/kg, 5 PEEP and a respiratory rate of 15 bpm with an I:E-ratio of 1:2. Salbutamol/ipratropium bromide and magnesium sulphate will be administered at baseline (t=0h) and measurements will be made for an hour. At T=1h the first dose of 0.5 mg/kg enoximone will be administered and will be repeated at T=2h and T=3h. Ventilator derived variables will be obtained every fifteen minutes and echocardiography, arterial and central venous bloodgas analyses every hour until t=6h.

Official Title
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The Effects of Enoximone in Acute Exacerbation COPD

Conditions
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COPD Exacerbation, Enoximone, Phosphodiesterase Inhibitor

Intervention / Treatment
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* Drug: Enoximone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with an AE-COPD for which intubation occurred within 24 hours before enrolment. Exclusion Criteria: Patients with known asthma or interstitial lung disease (ILD) Known neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Guillain-Barre and Dementia Hypertrophic obstructive cardiomyopathy (HOCM) Severe aortic stenosis with aortic valve area < 1cm2 Known ventricular arrhythmias Severe kidney disorders with Glomerular Filtration Rate (GFR) < 30 Severe liver insufficiency with spontaneous PT/INR > 1.5 Pregnancy Lactation High dose-diuretics use (daily dose of >480 mg furosemide)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enoximone<br>Patients will receive three times a dose of 0.5 mg/kg enoximone with a one-hour-interval. | Drug: Enoximone<br>* Patients will receive three times a dose of 0.5 mg/kg enoximone with a one-hour-interval.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PEEP | Reduction in intrinsic PEEP, in cmH2O | within 6 hoursmeasured every 15 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung compliance | ml/H2O | within 6 hours, measured every hour | 
| Airway resistence | cmH2O/L/sec | within 6 hours, measured every hour | 
| VEI | ml | within 6 hours, measured every hour | 
| VCO2 | ml/min | within 6 hours, measured every hour | 
| etCO2 | kPa | within 6 hours, measured every hour | 
| Vd/Vt | Measured by Bohr-equation, in percentage | within 6 hours, measured every hour | 
| FiO2 | percentage | within 6 hours, measured every hour | 
| Shunt fraction | measured by Fick-equation, using the SvO2, in percentage | within 6 hours, measured every hour | 
| Cardiac Output | Measured by echocardiography (LVOT VTI), ml/hr | within 6 hours, measured every hour | 
| RVSP | Measured by echocardiography, in mmHg | within 6 hours, measured every hour | 
| TAPSE | Measured by echocardiography, in mm | within 6 hours, measured every hour | 
| MAPSE | Measured by echocardiography, in mm | within 6 hours, measured every hour | 
| LV Ejection Fraction | Measured by echocardiography, in percentage | within 6 hours, measured every hour | 
| Bloodgas analysis | Arterial bloodgas analysis and central venous gas analysis (through catheter placed in superior vena cava) | within 6 hours, measured every hour |