The Effects of Enoximone in Acute Exacerbation COPD

NCT04420455 — Phase 4, Terminated, 3 participants, Rijnstate Hospital

ClinicalTrials Daily · Areas · Conditions · Drugs · Sponsors ·

Registry	NCT04420455
Status	Terminated - A limited number of inclusions due to the Covid-pandemic
Phase	Phase 4
Study type	Interventional; na, single group, masking: none, treatment
Enrollment	3 (Actual)
Sponsor	Rijnstate Hospital (Other)
Conditions	COPD Exacerbation, Enoximone, Phosphodiesterase Inhibitor
Interventions	Enoximone (Drug)
Dates	start 2020-05-12, primary completion 2021-12-21, completion 2021-12-21, first posted 2020-06-09, last updated 2022-01-13
Locations	1 site in Netherlands

-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.

Expand all sections · Collapse all

+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.

+Arms and interventions

Arm	Type	Interventions	Description
Enoximone	Experimental	Drug: Enoximone	Patients will receive three times a dose of 0.5 mg/kg enoximone with a one-hour-interval.

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

+Outcome measures

Primary outcomes

PEEP [within 6 hoursmeasured every 15 minutes]: Reduction in intrinsic PEEP, in cmH2O

Secondary outcomes

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

+Eligibility

Sex: All, ages: 18 Years to any

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)

+Locations (1)

Facility	City	Country	Status
M.V. Koning	Arnhem, M	Netherlands