MedPath

The Effects of Enoximone in Acute Exacerbation COPD

Phase 4
Terminated
Conditions
COPD Exacerbation
Enoximone
Phosphodiesterase Inhibitor
Interventions
Registration Number
NCT04420455
Lead Sponsor
Rijnstate Hospital
Brief 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.

Detailed 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 & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
3
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
EnoximoneEnoximonePatients will receive three times a dose of 0.5 mg/kg enoximone with a one-hour-interval.
Primary Outcome Measures
NameTimeMethod
PEEPwithin 6 hoursmeasured every 15 minutes

Reduction in intrinsic PEEP, in cmH2O

Secondary Outcome Measures
NameTimeMethod
Airway resistencewithin 6 hours, measured every hour

cmH2O/L/sec

VCO2within 6 hours, measured every hour

ml/min

etCO2within 6 hours, measured every hour

kPa

FiO2within 6 hours, measured every hour

percentage

Vd/Vtwithin 6 hours, measured every hour

Measured by Bohr-equation, in percentage

Lung compliancewithin 6 hours, measured every hour

ml/H2O

VEIwithin 6 hours, measured every hour

ml

Shunt fractionwithin 6 hours, measured every hour

measured by Fick-equation, using the SvO2, in percentage

Cardiac Outputwithin 6 hours, measured every hour

Measured by echocardiography (LVOT VTI), ml/hr

RVSPwithin 6 hours, measured every hour

Measured by echocardiography, in mmHg

TAPSEwithin 6 hours, measured every hour

Measured by echocardiography, in mm

MAPSEwithin 6 hours, measured every hour

Measured by echocardiography, in mm

LV Ejection Fractionwithin 6 hours, measured every hour

Measured by echocardiography, in percentage

Bloodgas analysiswithin 6 hours, measured every hour

Arterial bloodgas analysis and central venous gas analysis (through catheter placed in superior vena cava)

Trial Locations

Locations (1)

M.V. Koning

🇳🇱

Arnhem, M, Netherlands

© Copyright 2025. All Rights Reserved by MedPath