Clinical trial NCT00312273: Aminophylline in Bradyasystolic Cardiac Arrest
Official title: Aminophylline in Bradyasystolic Cardiac Arrest: A Randomized Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cardiac Arrest
Keywords: Heart Arrest
Cardiopulmonary Resuscitation
Aminophylline
Bradycardia
Humans
Emergency Medical Services
Lead sponsor: Vancouver General Hospital
Sponsor class: OTHER
Collaborators: name: Heart and Stroke Foundation of Canada
name: Vancouver Coastal Health Research Institute
First posted: 2006-04-07
Enrollment: 966
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the effect of aminophylline in patients with out-of-hospital bradyasystolic cardiac arrest.

Detailed description: Out-of-hospital cardiac arrest treated by emergency medical services has an estimated incidence of 54.99 per 100,000 person years, which translates to some 155,000 episodes annually in the United States. Bradyasystole is the first recorded rhythm in up to 52 percent of cardiac arrests, and many additional patients with an initial cardiac arrest rhythm of ventricular fibrillation deteriorate to bradyasystole after defibrillation efforts. Survival to hospital discharge occurs in less than 3 percent of patients presenting with bradyasystole; however, due to its frequency, this rhythm accounts for over 17 percent of all cardiac arrest survivors. As a result, even a small improvement in survival from bradyasystolic cardiac arrest would result in thousands of lives saved annually.

Adenosine is an endogenous purine nucleoside that depresses the sinoatrial node, blocks atrioventricular conduction, inhibits the pacemaker activity of the His-Purkinje system and attenuates the effects of catecholamines. Since adenosine is produced and released by myocardial cells during ischemia and hypoxia, it may be a reversible factor in the etiology or perpetuation of bradyasystole. Aminophylline is a competitive antagonist of adenosine. The use of aminophylline for bradycardia and heart block has been described, and a number of anecdotal reports and small studies have been published on the use of aminophylline in cardiac arrest. We undertook this study to evaluate the effect of aminophylline during cardiopulmonary resuscitation (CPR) of patients with out-of-hospital bradyasystolic cardiac arrest unresponsive to initial therapy.

Eligibility criteria: Inclusion Criteria:

* Cardiac arrest
* Bradyasystole either as the presenting rhythm or as a rhythm developing during the course of the resuscitation
* Endotracheally intubated and ventilated with 100% oxygen
* Intravenous (IV) access established
* Bradyasystolic without palpable pulses after 1 mg of epinephrine and 3 mg of atropine.

Exclusion Criteria:

* A do-not-resuscitate directive
* Pregnancy
* Evidence of hemorrhage, trauma or hypothermia as a cause of the cardiac arrest
* Renal dialysis
* Theophylline hypersensitivity
* Patients taking an oral theophylline product
* Resuscitations directed by a paramedic student under practicum supervision

Primary outcomes:
measure: The return of spontaneous circulation (ROSC), defined as the development of a palpable pulse of any duration.
Secondary outcomes:
measure: Maximum duration of ROSC (the duration of the longest episode of sustained pulse return)
measure: ROSC duration by survival analysis
measure: Survival to hospital admission
measure: Survival to hospital discharge
measure: Length of hospital stay
measure: Non-sinus tachyarrhythmias in the first 24 hours after study drug administration
measure: Seizures in the first 24 hours after study drug administration
measure: Neurologic outcome
measure: Proportion of subjects receiving one versus two doses of study drug
measure: Proportion of subjects achieving ROSC with initial-rhythm bradyasystole versus bradyasystole which developed after paramedic arrival.
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
Study officials:
affiliation: Department of Emergency Medicine, Vancouver General Hospital
name: Riyad B Abu Laban, MD, MHSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Abu-Laban RB, McIntyre CM, Christenson JM, van Beek CA, Innes GD, O'Brien RK, Wanger KP, McKnight RD, Gin KG, Zed PJ, Watts J, Puskaric J, MacPhail IA, Berringer RG, Milner RA. Aminophylline in bradyasystolic cardiac arrest: a randomised placebo-controlled trial. Lancet. 2006 May 13;367(9522):1577-84. doi: 10.1016/S0140-6736(06)68694-7.