Clinical Trial: Combined Vasopressin, Methylprednisolone, and Epinephrine for Inhospital Cardiac Arrest

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase 2, Single-Center, Placebo-Controlled Study of the Effects of Combined Administration of Vasopressin, Methylprednisolone, and Epinephrine During Cardiopulmonary Resuscitation on Survival After Ca

Brief Summary: A randomized controlled trial did not show benefit of vasopressin versus epinephrine in inhospital cardiac arrest. Preceding laboratory data suggest that combined vasopressin and epinephrine ensure long-term survival and neurologic recovery. Also, postresuscitation abnormalities mimic severe sepsis. The investigators hypothesized that combined vasopressin and epinephrine during cardiopulmonary resuscitation (CPR), and steroid supplementation during and after (when required) CPR may improve survival in cardiac arrest.

Detailed Summary:

Inhospital cardiac arrest still constitutes an important clinical problem with survival to discharge ranging within 0-42% (most common range = 15-20%). Survival after witnessed, pulseless ventricular fibrillation/tachycardia(VF/VT) that is responsive to one or two direct current countershock(s) may exceed 30%. However, survival after inhospital asystole, pulseless electrical activity, or refractory VF/VT (defined as not responsive to two countershocks) may be substantially lower (< 5-10%). As in nonsurvivors, both endogenous vasopressin and adrenocorticotrophin are reduced compared to survivors, we hypothesized that the addition of exogenous vasopressin and steroids to the standard CPR protocol may increase the rates of both the return of spontaneous circulation (ROSC) and of post-arrest survival. The mechanistic basis of this hypothesis comprises the simultaneous activation of adrenergic and vasopressin receptors, in conjunction with a potential steroid-mediated enhancement of the vascular reactivity to epinephrine.

Adult in-patients with cardiac arrest not responsive to two direct current countershocks (when applicable) or asystole or pulseless electrical activity are randomized to receive either arginine vasopressin (Pitressin, 20 IU/CPR cycle for the first 5 CPR-cycles in non-VF/VT and from the second to sixth CPR-cycle in VF/VT) plus epinephrine (1 mg/CPR-cycle) plus methylprednisolone (single dose = 40 mg during the first and second CPR-cycle in non-VF/VT and VF/VT, respectively) or normal saline-placebo plus epinephrine (1 mg/CPR-cycle) plus normal saline-placebo during the first 5 or second to sixth CPR-cycles. Further CPR-vasopressor treatment includes epinephrine (1 mg/CPR-cycle) for both groups. Apart from the initial, combined drug administration in the study group, CPR is conducted in full concordance with the 2005 European Resuscitation Council Guidelines
Sponsor: University of Athens

Current Primary Outcome: 1) Return of Spontaneous Circulation for > 15 min and 2) Survival to discharge either to home or to a rehabilitation facility. [ Time Frame: 60 days (actual) ]

Original Primary Outcome:

  • Return of spontaneous circulation for ≥ 15 min.
  • Survival to discharge either to home or to a rehabilitation facility.


Current Secondary Outcome:

  • Sequential Organ Dysfunction Assessment Score during follow-up. Organ failure free days. [ Time Frame: 60 days (actual) ]
  • Neurological status during follow-up. [ Time Frame: 60 days (actual) ]
  • Cerebral performance during follow-up and at discharge. [ Time Frame: 60 days (actual) ]
  • Peri-arrest arterial pressure [ Time Frame: 30 minutes (actual) ]
  • Plasma cytokine concentration [ Time Frame: 7 days (actual) ]


Original Secondary Outcome:

  • Sequential Organ Dysfunction Assessment Score during follow-up.
  • Neurological status during follow-up.
  • Cerebral performance during follow-up and at discharge.


Information By: University of Athens

Dates:
Date Received: December 14, 2006
Date Started: June 2006
Date Completion:
Last Updated: January 8, 2016
Last Verified: January 2016