Pre-Resuscitation Intra-Nasal Cooling Effectiveness (PRINCE) Study

BeneChill completed the first randomized intra-arrest cooling study performed using the RhinoChill™ Intra-Nasal Cooling System, a novel intra-nasal cooling method and showed much faster and earlier cooling in treated patients and significantly higher neurologically intact survival-to-discharge rate in many patients. The Pre-Resuscitation Intra-Nasal Cooling Effectiveness (PRINCE) study involved 200 patients and was conducted by 15 Emergency Medical Systems (EMS) in Belgium, Germany, Italy, Czech Republic and Sweden. (Scroll down for a list of the site investigators).  The aim was to determine safety and efficacy of intra-nasal cooling during ongoing resuscitation of cardiac arrest patients even before the return of spontaneous circulation (ROSC). The findings were presented in Orlando, FL during the recent American Heart Association’s Resuscitation Science Symposium “Best of the Best” presentations.

The trial was designed to determine the safety and effectiveness of early cooling initiated at the site of the arrest. The RhinoChill™ Intra-Nasal Cooling System technology enabled cooling to start much earlier than is possible with conventional methods used in a hospital setting. Additional endpoints included cooling rates, time to achieve target temperature, ease of use in the field, resuscitation rates, survival and neurologically intact survival. EMS personnel recruited adults over 18 years old who were in cardiac arrest and not hospitalized during resuscitation.  All patients who were deemed eligible for advanced cardiac life support (ACLS) were included as long as the arrest was witnessed and cardiopulmonary resuscitation (CPR) was initiated within 20 minutes of collapse.

The results of the study included:

• Cooling was initiated 23 minutes following arrest and lowered brain temperature (tympanic) (34.2 °C vs. 35.5°C) and body (core) temperature (35.1°C vs. 35.8°C ) significantly by ER arrival. 
• Time to target tympanic temperature of 34 degrees was three hours faster and time to target core temperature was two hours faster in patients cooled intra-nasally in the field compared to those receiving hospital cooling alone.
• Survival to discharge was higher in treated patients admitted to hospital (46.7% vs 31%) and significantly higher in those in whom CPR was initiated within 10 minutes of collapse, irrespective of rhythm (59.1% vs 29.4%).
• Neurologically intact survival to discharge was higher in treated patients admitted to the hospital (36.7% vs 21.4%) and significantly higher in those in whom CPR was initiated within 10 minutes of collapse, irrespective of rhythm (45.5% vs 17.6%).
• Intra-nasal cooling with the RhinoChill™ Intra-Nasal Cooling System was feasible and safe during an arrest.  Nasal discoloration was the most commonly reported adverse event occurring in 13 patients. This resolved spontaneously in all patients who were successfully resuscitated.

PRINCE Study Sites and Investigators

Click for abstract (PDF); Click for presentation (PowerPoint).

Additional Clinical Studies

RhinoChill™ Intra-Nasal Cooling System ER Cooling Study

BeneChill conducted a single-arm safety and feasibility study of early cooling with the RhinoChill™ Intra-Nasal Cooling System in patients resuscitated from cardiac arrest. Eighty-four patients were treated at 11 sites in Europe from September 2007 through August 2008. Patients were enrolled in the study as soon as they were admitted to the hospital facility treating cardiac arrest in the emergency room (ER), cardiac catheterization lab, or intensive care unit (ICU) and found to meet study inclusion criteria. Thirty-three percent of patients experienced an in-hospital cardiac arrest and the remaining 67% were admitted following an out of hospital arrest.

The RhinoChill™ Intra-Nasal Cooling System was used to cool patients as soon as it was feasible and cooling was continued until target temperature was reached or when standard systemic cooling methods were ready to be initiated. The RhinoChill™ Intra-Nasal Cooling System was used to begin cooling 35 minutes (median value) after patients were admitted to the hospital. A cooling gradient between temperatures observed with relative cooling rates of 2.4, 1.6, and 0.9°C/hr measured in the tympanon, esophagus or peripheral artery and bladder or rectum, respectively. A therapeutic temperature of 34°C was reached within 27 and 51 minutes of use for the tympanon and whole body, respectively. There was a single serious device-related event in which a patient in irreversible cardiogenic shock underwent cold-related tissue damage to the peri-nasal region.

RhinoChill™ Intra-Nasal Cooling System Neuro-ICU Cooling Study

BeneChill conducted a single-arm safety and feasibility study of cooling induction with the RhinoChill™ Intra-Nasal Cooling System in patients requiring therapeutic hypothermia after experiencing a cerebral ischemic event. Fifteen patients were treated at three sites in the US from November 2007 through February 2009. Patients were enrolled in the study after admission to the Neuro-ICU and therapeutic hypothermia was ordered to treat either elevated intra-cranial pressure or neurogenic fever. Eight (53%) patients underwent hemorrhagic stroke or other cerebral hemorrhagic event, six patients experienced a large ischemic stroke and one patient had traumatic brain injury. Three patients undergoing a hemorrhagic event also sustained secondary brain trauma.

The RhinoChill™ Intra-Nasal Cooling System was used to cool patients for one hour to induce cooling while systemic cooling methods were being readied for use.  A cooling gradient between temperatures observed with relative cooling rates of 2.2, 1.5, and 1.1°C/hr measured in the tympanon, brain or core (primarily bladder), respectively. The initial average intracranial pressure was 16mmHg and dropped an average of 5.2mmHg, or 32.5% over the hour of RhinoChill™ cooling. Brain cooling was as effective in febrile patients as it was afebrile. Additionally, brain cooling was effective in two morbidly obese patients that underwent very little systemic cooling due to their large mass.

There was a single serious device/procedure-related event in which a comatose patient underwent an increase in mean arterial pressure from 75 to 94mmHg within the first 15 minutes of RhinoChill™ cooling which was sustained for an additional 15 minutes. Pressure normalized after cooling was stopped and sedation was administered.

Future Clinical Trials

On-going, physician-sponsored studies include the PRINCESS cardiac arrest study and a small stroke study. The aim of the PRINCESS study is to initiate cooling much earlier during the arrest in an attempt to improve outcomes further. The purpose of the the small stroke study, which is being conducted in Heidelberg, Germany, is to compare ease-of-use, cooling efficacy and hemodynamics using different cooling techniques.

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