Paroxysmal or persistent, non-valvular, atrial fibrillation MedDRA version: 20.0 Level: PT Classification code 10003658 Term: Atrial fibrillation System Organ Class: 10007541 - Cardiac disorders MedDRA version: 20.0 Level: LLT Classification code 10034039 Term: Paroxysmal atrial fibrillation System Organ Class: 10007541 - Cardiac disorders MedDRA version: 20.0 Level: LLT Classification code 10071667 Term: Persistent atrial fibrillation System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: Dopram®
Pharmaceutical Form: Solution for injection
Sponsors
Ruprecht-Karls University Heidelberg Medical Faculty, University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 18 – 80 years, 2. Patient meets in-house eligibility criteria for non-emergent, electrical or pharmacological cardioversion (absence of AF-inducing medical conditions such as e.g. valvular disease, sufficient anticoagulation, and/or exclusion of cardiac thrombus), 3. Available previous ECG in sinus rhythm to allow for an assessment of QT time, 4. Ability to understand and willingness to comply with study interventions, and 5. Voluntarily signed informed consent after full explanation of the study to the patient. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Any participation in a clinical drug trial within 5 times the documented terminal half-life of the respective active drug or if half-life is unknown within the last four weeks before inclusion, 2. Any physical disorder as judged by the investigator that could interfere with the patient’s safety during the clinical trial or with the study objectives, 3. Inability to communicate well with the investigator due to language problems or poor mental development, 4. Pregnancy or lactation, 5. Intake of antiarrhythmic agents as co-medication (Vaughan Williams classification), except class II beta-blockers, within less than 5 half-lives of the respective drug as related to planned exposure: class Ia: e.g. quinidine, ajmaline, procainamide, or disopyramide, class Ib: e.g. lidocaine, phenytoin, mexiletine, or tocainide, class Ic: e.g. encainide, flecainide, propafenone, or moricizine, class III: e.g. amiodarone, sotalol, ibutilide, dofetilide, dronedarone, or vernakalant, class IV: e.g. verapamil ordiltiazem, class V: e.g. adenosine, digoxin, or digitoxin, unclassified: ranolazine, 6. Any adenosine like drugs (e.g. ticagrelor) within less than 5 half-lives of the respective drug, 7. Any magnesium intake (> 500 mg) within 4 h of planned exposure, if magnesium has been applied within 24 h prior to planned exposure magnesium blood level must not higher than the upper limit of normal (+ 10%), 8. Any theophylline intake within 3 d as related to planned exposure, 9. Contraindication for doxapram use present such as a) known intolerance to doxapram, b) systolic blood pressure 170 mmHg, c) diastolic blood pressure 100 mmHg, d) Heart rate 430 ms, female participants with QTc > 450ms) or short QT syndrome in an ECG in sinus rhythm recorded. 15. Body weight > 140 kg
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Antiarrhythmic potential for cardioversion from AF to SR after i.v. administration of doxapram;Secondary Objective: • Recommended i.v. doxapram dose for cardioversion • Time to cardioversion from AF to SR after i.v. doxapram administration • Time to recurrence of AF within 7 ± 2 d of cardioversion • Doxapram PK after i.v. administration of one or two equal consecutive bolus doses • Doxapram PK after continuous i.v. administration over 8 h • Safety and tolerability of doxapram after i.v. administration ;Primary end point(s): Number of patients with cardioversion from AF to SR (yes/no) within 6 h after i.v. doxapram as measured by 12-lead ECG. For the primary objective SR is defined as any rhythm originating in the atrium, the junctional area or the His bundle, which is not atrial fibrillation.;Timepoint(s) of evaluation of this end point: 6 h (i.v.) after application depending on the route of administration. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Time to cardioversion from AF to SR as documented by 12-lead ECG • Persistence of rhythm over 7 ± 2 d of cardioversion as measured by 7-d Holter ECG • Doxapram PK: plasma concentrations of doxapram and derived PK parameters after bolus injection or continuous i.v. infusion (e.g. highest concentration (Cmax), time to highest concentration (Tmax), area under the curve from 0 to 6 h (AUC0-6) after i.v. administration, and half-life (t1/2). • AEs as assessed by open questions and predefined procedures including assessment of well-being, physical examination, vital signs, and laboratory measurements.;Timepoint(s) of evaluation of this end point: From exposure till end of study | — |
Countries
Germany
Contacts
Public ContactDepartment of Clinical Pharmacology
University of Heidelberg
Outcome results
None listed