The Effects of Enoximone in Acute Exacerbation COPD

COPD Exacerbation Clinical Trial

Official title:

The Effects of Enoximone in Acute Exacerbation COPD

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04420455
• Other study ID #: 2019-1432
• Status: Terminated
• Phase: Phase 4
• Start date: May 12, 2020
• Est. completion date: December 21, 2021

Study information

• Verified date: December 2021
• Source: Rijnstate Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: December 21, 2021
• Est. primary completion date: December 21, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• COPD Exacerbation
• Enoximone
• Phosphodiesterase Inhibitor

Intervention

Drug:
• Enoximone
Patients will receive three times a dose of 0.5 mg/kg enoximone with a one-hour-interval.

Locations

Country	Name	City	State
Netherlands	M.V. Koning	Arnhem	M

Sponsors (1)

Lead Sponsor	Collaborator
Rijnstate Hospital

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PEEP	Reduction in intrinsic PEEP, in cmH2O	within 6 hoursmeasured every 15 minutes
Secondary	Lung compliance	ml/H2O	within 6 hours, measured every hour
Secondary	Airway resistence	cmH2O/L/sec	within 6 hours, measured every hour
Secondary	VEI	ml	within 6 hours, measured every hour
Secondary	VCO2	ml/min	within 6 hours, measured every hour
Secondary	etCO2	kPa	within 6 hours, measured every hour
Secondary	Vd/Vt	Measured by Bohr-equation, in percentage	within 6 hours, measured every hour
Secondary	FiO2	percentage	within 6 hours, measured every hour
Secondary	Shunt fraction	measured by Fick-equation, using the SvO2, in percentage	within 6 hours, measured every hour
Secondary	Cardiac Output	Measured by echocardiography (LVOT VTI), ml/hr	within 6 hours, measured every hour
Secondary	RVSP	Measured by echocardiography, in mmHg	within 6 hours, measured every hour
Secondary	TAPSE	Measured by echocardiography, in mm	within 6 hours, measured every hour
Secondary	MAPSE	Measured by echocardiography, in mm	within 6 hours, measured every hour
Secondary	LV Ejection Fraction	Measured by echocardiography, in percentage	within 6 hours, measured every hour
Secondary	Bloodgas analysis	Arterial bloodgas analysis and central venous gas analysis (through catheter placed in superior vena cava)	within 6 hours, measured every hour