Medical Device Daily

Cardium Therapeutics and its subsidiary InnerCool Therapies (both San Diego) reported the enrollment of the first patient in the Rapid Intravascular Cooling in Myocardial Infarction as Adjunctive to Percutaneous Coronary Intervention (RAPID MI-ICE) study at Lund University Hospital (Sweden).

The purpose of the study is to assess the safety and potential utility of early and rapid cooling of patients with myocardial infarction (MI, or heart attack). Previous clinical data suggest early and rapid cooling with InnerCool's endovascular catheter-based temperature modulation system immediately prior to reperfusion during angioplasty and stent procedures holds great promise for heart attack patients as a potential means of reducing cardiac tissue injury following reperfusion.

Brad Klos, VP of sales and marketing for InnerCool, told Medical Device Daily that it was previously believed that hypothermia could be induced before or after angioplasty to reduce tissue damage following a heart attack, but that researchers have since learned that is not the case.

"You've got to cool them very well before the angioplasty. You've got to get the patient cooled to 35-degrees Celsius or lower before the balloon goes up," Klos said.

The RAPID MI-ICE study is expected to enroll about 20 patients who present within six hours of heart attack and require angioplasty and stent procedures in order to restore blood flow to the heart.

Eligible patients will be randomized to one of two treatment protocols, and the effects on heart tissue damage will be compared.

Patients randomized to the cooling part of the study (hypothermia) will receive an iced saline infusion in addition to the use of the InnerCool Accutrol endovascular catheter, which contains an integrated temperature sensor that accurately measures the patient's core body temperature.

Patients assigned to the normothermia part of the study will receive routine standard of care without induced hypothermia. The trial will employ cardiac MRI to provide an assessment of the damage to the heart, as measured by infarct size, within days of the heart attack.

Klos said the enrollment period for the single-site study is expected to be about 12 months.

Researchers from the Interventional Cardiology Center at Lund University Hospital presented their pre-clinical results at the Transcatheter Cardiovascular Therapeutics 2006 annual meeting in Washington last year. In a porcine heart attack model, the investigators evaluated rapid cooling, induced by a combination of cold saline infusion along with InnerCool's catheter-based system, prior to or coincident with angioplasty and stent procedures.

The data showed that cooling prior to reperfusion reduced overall infarct size (a measure of tissue damage) by 40% compared to the control group. In addition, a meta-analysis that included data from the Intravascular Cooling Adjunctive to Percutaneous Coronary Intervention (ICE-IT) study, a 228-patient study, suggested that a 20% to 40% reduction of infarct size is possible when patients are cooled early and rapidly with an endovascular temperature modulation system as an adjunct to angioplasty and stent procedures.

"Preclinical and preliminary clinical data suggest that endovascular temperature modulation therapy may have the potential to enable interventional cardiologists to dramatically reduce heart tissue damage following a heart attack," said David Erlinge, MD, PhD, of the Lund University Cardiology Center.

Christopher Reinhard, CEO and chairman of Cardium and InnerCool, said, "We believe the InnerCool Accutrol endovascular catheter is best-in-class. It has the power to provide for rapid cooling and, with the unique integrated temperature sensor, it accurately measures the patient's core body temperature. This integrated combination of features is essential to handle the performance requirements of the RAPID MI-ICE study . . . "

According to Cardium, numerous scientific and medical articles have described the usefulness of temperature modulation, such as induced hypothermia, which is designed to protect endangered cells, prevent tissue death and preserve organ function following acute events associated with severe oxygen deprivation such as stroke or cardiac arrest.

Therapeutic hypothermia is believed to work by protecting critical tissues and organs — such as the brain, heart and kidneys — following ischemic or inflammatory events, by lowering metabolism and preserving cellular energy stores, thereby potentially stabilizing cellular structure and preventing or reducing injuries at the cellular, tissue and organ level, the company said.

InnerCool's endovascular approach to temperature modulation is based on a single-use flexible metallic catheter and a fully-integrated cooling system, which allows for rapid and controlled cooling and re-warming.

Its Celsius Control System integrates a number of features, including a slim catheter profile, a highly efficient flexible metallic heat transfer element, a built-in temperature monitoring sensor, and a programmable console capable of rapidly and controllably inducing, maintaining and reversing therapeutic cooling, according to the company.

The system has received FDA 510(k) clearance for use in inducing, maintaining and reversing mild hypothermia in neurosurgical patients, both in surgery and in recovery or intensive care. The system has also received FDA clearance for use in cardiac patients in order to achieve or maintain normal body temperatures during surgery and in recovery/ intensive care, and as an adjunctive treatment for fever control in patients with cerebral infarction and intracerebral hemorrhage. Potential additional applications of the technology include endovascular cooling for cardiac arrest, acute ischemic stroke and MI (heart attack).

Klos said one challenge of using temperature modulation to reduce tissue damage following a heart attack is being able to cool the patient in a cath lab while they are awake. That's why InerCool's catheter-based approach works well, he said.

"By integrating the temperature sensor in the catheter we get good core feedback in the machine so we really know what the patient's actual body temperature is," he said.

Earlier this month Cardium reported the closing of a $21.5 million private placement financing with institutional investors. The investment included the sale and issuance of roughly 8.6 million shares of common stock and warrants to buy up to about 3 million shares of common stock (Medical Device Daily, March 13, 2007).

Cardium and its subsidiaries, InnerCool and the Tissue Repair Company, are primarily focused on the development of therapeutic products and devices for cardiovascular, ischemic and related indications.