The Effects of Enoximone in Acute Exacerbation COPD

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.

Study Overview

• Status: Terminated
• Conditions: COPD Exacerbation; Enoximone; Phosphodiesterase Inhibitor
• Intervention / Treatment: Drug: Enoximone

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • M
    • Arnhem, M, Netherlands
      • M.V. Koning

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rijnstate Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2020
• Primary Completion (Actual): December 21, 2021
• Study Completion (Actual): December 21, 2021

Study Registration Dates

• First Submitted: January 31, 2020
• First Submitted That Met QC Criteria: June 3, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): January 13, 2022
• Last Update Submitted That Met QC Criteria: December 23, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Enoximone
• Other Study ID Numbers: 2019-1432

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Time Frame: after publication
• IPD Sharing Access Criteria: upon reasonable request, available by the researchers
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No