Ignite Creation Date:
2024-07-17 @ 12:00 PM
Last Modification Date:
2024-10-26 @ 3:33 PM
Study NCT ID:
NCT06473116
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-25
First Post:
2024-06-05
Brief Title:
Epinephrine Versus Isoprenaline During Out-of-Hospital Cardiac Arrest With Asystole
Sponsor:
University of Southern Denmark
Organization:
University of Southern Denmark
Study Overview
Official Title:
Epinephrine Versus Isoprenaline During Out-of-Hospital Cardiac Arrest With Asystole A Randomized Clinical Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
EPISO
Brief Summary:
Background During out-of-hospital cardiac arrest OHCA the patient presents with either a shockable or a non-shockable rhythm Early cardiopulmonary resuscitation CPR and defibrillation of the shockable rhythm may increase chance of survival to more than 50 however if untreated the heart rhythm will deteriorate to a non-shockable rhythm with dismal survival outcomes of 1-5 Isoprenaline is a pro-arrhythmic drug used to treat bradycardia and has a structural resemblance to epinephrine which is the drug of choice during cardiac arrest with non-shockable rhythms
Aims To evaluate whether intravebous IV administration of isoprenaline increases the chance of return of spontaneous circulation ROSC to hospital arrival main outcome compared with IV epinephrine
Study design A randomized-controlled trial
Setting The study will be conducted in the Region of Southern Denmark which has about 12 million inhabitants and an annual incidence of 1200 OHCAs The study will include bystander-witnessed patients with asystole at the arrival of the emergency medical services EMS Randomization will take place on arrival of the EMS where the OHCA patients randomly will be assigned to receive an intravenous injection of isoprenaline 600 µg or an intravenous injection of adrenaline 1 mg in a 11 ratio The study will include 1178 OHCAs over a time period of about 35 years
Aims To evaluate whether intravebous IV administration of isoprenaline increases the chance of return of spontaneous circulation ROSC to hospital arrival main outcome compared with IV epinephrine
Study design A randomized-controlled trial
Setting The study will be conducted in the Region of Southern Denmark which has about 12 million inhabitants and an annual incidence of 1200 OHCAs The study will include bystander-witnessed patients with asystole at the arrival of the emergency medical services EMS Randomization will take place on arrival of the EMS where the OHCA patients randomly will be assigned to receive an intravenous injection of isoprenaline 600 µg or an intravenous injection of adrenaline 1 mg in a 11 ratio The study will include 1178 OHCAs over a time period of about 35 years
Detailed Description:
Background Out-of-hospital cardiac arrest OHCA is the leading cause of death in industrialized countries During OHCA the patient will present with either a non-shockable or a shockable rhythm A shockable rhythm is treated by defibrillation which means delivering an electrical shock through the heart to reestablish normal cardiac electric activity If a shockable rhythm is defibrillated early chances of survival can exceed 50 However if the shockable rhythm remains untreated it will deteriorate into a non-shockable rhythm with dismal survival rates of 1-5 Epinephrine increases the chance of return of spontaneous circulation ROSC however there is increasing evidence that use of epinephrine is associated with severe neurological impairment in survivors Isoprenaline is a pro-arrhythmic drug used to treat bradycardia The drug has structural resemblance to epinephrine however it has no effect on alfa-adrenoceptors in the cerebral bloodflow and only stimulates beta-adrenoceptors These pro-arrhythmic properties may induce cardiac electrical activity during OHCA with a non-shockable rhythm converting it to a shockable rhythm treatable by defibrillation while preserving microcirculatory cerebral blood flow
Hypothesis Injection of isoprenaline in bystander witnessed OHCAs with asystole increases the chance of ROSC at hospital arrival compared with the injection of epinephrine
Population According to the Danish Cardiac Arrest Registry the annual incidence of OHCAs in the Region of Southern Denmark is about 1200 half of which are bystander witnessed In the recent 2022 report the incidence of non-shockable first rhythm among these was 1044 out of 1233 patients 85 of which about 9 out of 10 had asystole Therefore an annual number of 450 bystander witnessed OHCAs with non-shockable rhythm could be eligible for study entry however despite eligibility previous study have found that about 20-25 of patients are not enrolled in similar OHCA trials and the expected annual number of enrollments will therefore be 360 OHCAs
Settings The study will take place in the Region of Southern Denmark The Region has 42 EMS ambulance stations and 6 physician-manned vehicles with a median response time of about 8 minutes The EMS ambulance has an emergency medical technician EMT and an EMT assistant trained in analysing shockablenon-shockable rhythms and administering intravenous drugs according to the advanced life support algorithm
Intervention On EMS arrival OHCA patients will be randomly assigned to receive an intravenous injection of isoprenaline or to receive an intravenous injection of adrenaline in a 11 ratio
Study design A randomized-controlled trial
Main outcome Main outcome is ROSC at hospital arrival Secondary outcomes are conversion from non-shockable to shockable rhythm 30-day survival with good neurological outcome Cerebral Performance Category Scale of 1 or 2
Power analysis Thirty-day survival among OHCAs with non-shockable rhythm is reported at 1-5 In a Danish study the conversion of a non-shockable rhythm to a shockable rhythm increased the rate of ROSC at hospital arrival to 145 compared with 84 for sustained non-shockable rhythms Thirty-day survival in the two groups were 42 versus 12 respectively According to this study about 1 in 8 non-shockable rhythms converted to a shockable rhythm Presuming that isoprenaline injection may double the conversion to shockable rhythm to 1 in 4 non-shockable rhythms this would increased chance of ROSC at hospital arrival to approximately 13 Therefore assuming a conservative difference estimate of about 5 estimate of 13 in the intervention group and 8 in the control group this study will require a total sample size of 1178 patients with 589 OHCAs in each group power value of 080 and significance level of 005 to evaluate the hypothesis An inclusion time of approximately 35 years is therefore to be expected
Hypothesis Injection of isoprenaline in bystander witnessed OHCAs with asystole increases the chance of ROSC at hospital arrival compared with the injection of epinephrine
Population According to the Danish Cardiac Arrest Registry the annual incidence of OHCAs in the Region of Southern Denmark is about 1200 half of which are bystander witnessed In the recent 2022 report the incidence of non-shockable first rhythm among these was 1044 out of 1233 patients 85 of which about 9 out of 10 had asystole Therefore an annual number of 450 bystander witnessed OHCAs with non-shockable rhythm could be eligible for study entry however despite eligibility previous study have found that about 20-25 of patients are not enrolled in similar OHCA trials and the expected annual number of enrollments will therefore be 360 OHCAs
Settings The study will take place in the Region of Southern Denmark The Region has 42 EMS ambulance stations and 6 physician-manned vehicles with a median response time of about 8 minutes The EMS ambulance has an emergency medical technician EMT and an EMT assistant trained in analysing shockablenon-shockable rhythms and administering intravenous drugs according to the advanced life support algorithm
Intervention On EMS arrival OHCA patients will be randomly assigned to receive an intravenous injection of isoprenaline or to receive an intravenous injection of adrenaline in a 11 ratio
Study design A randomized-controlled trial
Main outcome Main outcome is ROSC at hospital arrival Secondary outcomes are conversion from non-shockable to shockable rhythm 30-day survival with good neurological outcome Cerebral Performance Category Scale of 1 or 2
Power analysis Thirty-day survival among OHCAs with non-shockable rhythm is reported at 1-5 In a Danish study the conversion of a non-shockable rhythm to a shockable rhythm increased the rate of ROSC at hospital arrival to 145 compared with 84 for sustained non-shockable rhythms Thirty-day survival in the two groups were 42 versus 12 respectively According to this study about 1 in 8 non-shockable rhythms converted to a shockable rhythm Presuming that isoprenaline injection may double the conversion to shockable rhythm to 1 in 4 non-shockable rhythms this would increased chance of ROSC at hospital arrival to approximately 13 Therefore assuming a conservative difference estimate of about 5 estimate of 13 in the intervention group and 8 in the control group this study will require a total sample size of 1178 patients with 589 OHCAs in each group power value of 080 and significance level of 005 to evaluate the hypothesis An inclusion time of approximately 35 years is therefore to be expected
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None