Clinical trial NCT04420455: The Effects of Enoximone in Acute Exacerbation COPD
Official title: The Effects of Enoximone in Acute Exacerbation COPD
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: COPD Exacerbation
Enoximone
Phosphodiesterase Inhibitor
Lead sponsor: Rijnstate Hospital
Sponsor class: OTHER
First posted: 2020-06-09
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: PEEP
timeFrame: within 6 hoursmeasured every 15 minutes
Secondary outcomes:
measure: Lung compliance
timeFrame: within 6 hours, measured every hour
measure: Airway resistence
timeFrame: within 6 hours, measured every hour
measure: VEI
timeFrame: within 6 hours, measured every hour
measure: VCO2
timeFrame: within 6 hours, measured every hour
measure: etCO2
timeFrame: within 6 hours, measured every hour
measure: Vd/Vt
timeFrame: within 6 hours, measured every hour
measure: FiO2
timeFrame: within 6 hours, measured every hour
measure: Shunt fraction
timeFrame: within 6 hours, measured every hour
measure: Cardiac Output
timeFrame: within 6 hours, measured every hour
measure: RVSP
timeFrame: within 6 hours, measured every hour
measure: TAPSE
timeFrame: within 6 hours, measured every hour
measure: MAPSE
timeFrame: within 6 hours, measured every hour
measure: LV Ejection Fraction
timeFrame: within 6 hours, measured every hour
measure: Bloodgas analysis
timeFrame: within 6 hours, measured every hour
Other outcomes:
Locations:
city: Arnhem
country: Netherlands
facility: M.V. Koning
state: M
Study officials:
References: