Potential Clinical Applications

From medical conditions like hypertension and peripheral arterial disease (PAD) to sports performance enhancement - discover how IC Therapeutics' technology can be applied to a variety of potential clinical applications.

 


(For Non-invasive IC)

 Hypertension

The Problem: Hypertension, the condition of having high blood pressure, is a very common health condition in the U.S. population and throughout the world. It is a major risk factor for heart disease, stroke, and many other vascular conditions. Although a plethora of anti-hypertensive medications have been developed by the pharmaceutical industry, the treatment of hypertension is still inadequate, with many patients on multiple medications but still with poor blood pressure control. Moreover, drug treatment itself is associated with the risk of adverse reactions and side effects. Therefore, what is needed is a non-invasive, non-pharmacological method of improving vascular health and assisting with blood pressure control.

ICT’s Solution: The Company proposes to use a home- or ambulatory-based device, the BPShield™, to perform multiple ischemic conditioning treatments (non-invasive, limb cuff) on a repeated schedule, either daily or every other day, in patients with chronic hypertension or prehypertension. This simple, easy-to-operate device will also be able to measure blood pressure.



Peripheral Arterial Disease (PAD)

The Problem: Lower extremity claudication (cramp like pains) caused by atherosclerotic occlusive disease and poor circulation affects an estimated 10% of the population over age 70 years and 2% to 3% of individuals aged 37 to 69 years, with a significant impact on quality of life. The aging population in Western societies indicates that its prevalence will increase significantly over the next decades. Because the use of the most effective pharmacologic agents (e.g., Trental, Pletal) results only in a modest improvement in claudication, participation in a structured program of regular exercise, control of associated medical diseases or risk factors, surgical revascularization, and balloon angioplasty are currently considered the most beneficial management options. Unfortunately, many PAD patients are not good candidates for these invasive procedures, are unable to tolerate exercise programs, or respond poorly to medical treatments; these patients are desperate for a simple, easyto-use, treatment that would allow them to walk further without getting severe, claudication pain. The pro-vascular health effects conveyed by ischemic conditioning treatment could benefit any PAD patient.

ICT’s Solution: The Company proposes to perform multiple ischemic conditioning treatments (non-invasive, limb cuff) on a repeated schedule, either daily or every other day, through the use of a simple, easy-to-use device, the PAD-Shield™, that will be marketed directly to PAD patients. A more sophisticated version will incorporate tissue ischemia monitoring and will be sold to vascular labs, where PAD patients are diagnosed and receive treatments.


Major Surgeries in High-Risk Patients

The Problem: Currently, over 25 million noncardiac (and over 500,000 cardiac) surgical procedures are performed annually in the U.S., and it is estimated that over the next 15 years, the number will grow to 38 million. Despite advances in perioperative care, major thoracic and abdominal surgeries, such as cancer resection and aortic aneurysm repair, continue to be associated with significant perioperative morbidity (incidence 10-36 %) and mortality (incidence 5-11%), resulting in higher health care expenditure. This perioperative morbidity and mortality is primarily comprised of major cardiopulmonary events (MCPE), such as myocardial infarction, supraventricular arrhythmias, pneumonia and acute respiratory distress syndrome (ARDS).

Minimal progress has been made in understanding the etiology of these major cardiopulmonary events, and the primary method of preventing them is the assessment of a patient’s risk (based on the patient’s age, functional status, and other medical conditions) before surgery and then delaying or even cancelling surgery in those patients deemed to be at high risk. This may be a reasonable option in patients scheduled for elective procedures, but surgeons, anesthesiologists, and internists often face the dilemma of how to minimize the risk of perioperative complications when potentially life-saving surgeries (e.g., cancer resection, aortic aneurysm, etc.) need to be performed on intermediate- or high-risk patients. Preoperative administration of certain medications, such as beta blockers, statins, or certain inhalational anesthetic agents, has been proposed, but their associated side effects make their use inappropriate for some patients; moreover, they may only help to prevent injury to heart tissue, and their usefulness in nonvascular surgeries has not been established. Clearly, there continues to be an urgent need for a widely-applicable method of improving the perioperative outcomes of major surgical procedures in these high-risk patients.

ICT’s Solution: The Company proposes to use a hospital-based device, the Surgi-Shield™, to perform one or two ischemic conditioning treatments (non-invasive, limb cuff) on these high-risk patients, prior to undergoing their major surgical procedure. This device should be appealing to hospitals, physicians, and health care payers because its usage would help to decrease the incidence of perioperative complications, reduce length of stay, and consequently, reduce health care costs.


Pulmonary Arterial Hypertension (PAH)

The Problem: Pulmonary arterial hypertension (PAH), previously known as primary pulmonary hypertension (PPH), is a debilitating chronic disorder of the blood vessels in the lungs. The condition consists of vasoconstriction and vascular hypertrophy within the pulmonary artery, leading to obstruction and increased pulmonary vascular resistance (PVR). Marked elevations in pulmonary artery pressures ensue, resulting in right-sided heart overload, eventual heart failure, and death. Common presenting symptoms of PAH are fatigue, dyspnea, weakness, and inability to tolerate exertion. A qualitative assessment of functional status is useful in monitoring disease progression and assessing the response to treatment. The World Health Organization (WHO) functionalclassification is a useful tool in this regard. Other markers of disease severity include the Borg dyspnea index (BDI), which employs a scale from 0 = no impairment to 10 = severe impairment; the 6-minute walk test (6-MWT), a method of formal cardiopulmonary exercise testing that will reveal decreased exercise tolerance and maximum oxygen consumption in these patients; and cardiopulmonary hemodynamic variables (mPAP, PVR, cardiac output).

Oral drug therapies are effective in patients with mild to moderate PAH, whereas IV prostacyclin infusions are the treatment of choice for moderate to severe PAH. These medications are very expensive, and not all patients exhibit a good response to them. Gradually escalating exercise training is typically recommended, but patients with advanced disease are unable to perform any exercise without becoming markedly short of breath.

ICT’s Solution: The Company proposes to use a device, the PA-Shield™, to perform multiple ischemic conditioning treatments (non-invasive, limb cuff) on a repeated schedule, either daily or every other day, in PAH patients who are respond poorly to drug-based treatments and are unable to tolerate exercise training. A hospital-based version will be used to develop an individualized protocol (number of cycles, duration of ischemic periods, etc.) for a PAH patient. A simpler, home-based version can be programmed to perform this individualized protocol on the patient, at home.


(For Invasive IC)

Anastomotic leakage

The Problem: Depending on the tissues that are operated on, certain surgical procedures are plagued by complications that arise because of injury that specific tissues sustain from inadequate blood flow (ischemia) during the surgery. This is known as ischemia/reperfusion injury, or IRI. For example, in resection surgery for esophageal cancer, the portion of the esophagus with the tumor is removed, and the top of the stomach is pulled upwards and connected to the portion of the esophagus that remains. This new connection is referred to as an anastomosis. An unfortunate complication of this surgery is anastomotic leakage, which can occur in about 10% of cases and results in significantly higher mortality. The likelihood that this complication will occur has been shown to be related to how much ischemic injury the stomach tissue has sustained before the new connection is made and adequate blood flow is reestablished.

ICT’s Solution: The Company proposes to market a specialized vascular clamp device, known as O-Shield™, which will enable a surgeon to perform ischemic conditioning on the tissues that will become part of the anastomotic connection, by occluding and releasing the artery that supplies blood to that tissue. O-Shield™ will be a hospital-based device that includes a tissue ischemia monitoring component.

The resection surgery market is a significant one. Although the number of esophageal resection surgeries is not huge, anastomotic leakage and fistula formation (incidence 5-15%) is a dramatic and feared consequence, resulting in higher mortality and increased health care expenditures. Over 400,000 colon resection surgeries are performed annually in the U.S., and with an incidence of anastomotic leakage of 10%, approximately 40,000 cases of leakage are anticipated annually. One research study evaluated the increased costs that are incurred when anastomotic leaks occur; the mean cost of the primary hospital stay was $3890 in the control group and $12,650 in the leakage group.


Organ procurement for transplantation

The Problem: Organ transplantation is another good example of when ischemic injury to body tissues has been linked to poorer outcomes. With transplant surgery, the procured organ (heart, liver, kidney, etc.) is typically cooled and placed in preservative solutions, but in the absence of blood flow, the organ often still sustains ischemic injury that will directly impact its viability after it has been transplanted into the recipient patient. Clearly, there is a need for a device or treatment that can reduce the ischemic injury that these tissues sustain and improve the outcomes of these surgical procedures.

ICT’s Solution: The Company proposes to market the O-Shield™ device to surgeons to enable them to perform ischemic conditioning on the organ, immediately before procurement, by occluding and releasing the artery that supplies blood to that organ.

The primary market for this vascular clamp device is comprised of surgeons who perform organ procurement surgeries for organ transplantation. The Company plans to initially target sales to these surgeons and their associated surgical centers or hospitals. The organ procurement and transplantation market holds tremendous potential. Indeed, over $1.5 billion is spent annually in the U.S. on organ procurement and transportation alone. A widening gulf exists between the number of patients on organ waiting lists and the number of viable donor organs. A large part of this discrepancy is due to the effective lifespan of a procured organ; if the organ is not transplanted within a few hours of procurement, the likelihood of a successful transplantation and recipient survival is greatly reduced. If ischemic conditioning can empower the procured organ to survive outside the human body for a longer period of time, the number of possible transplants will increase. Currently, 12,000 organ procurement surgeries are performed annually, and the Company believes this number will continue to grow if methods can effectively increase
post-procurement organ survival time.


Ancillary Markets

Sports (performance enhancement)

Research studies suggest that some of the physiologic benefits of ischemic conditioning (improved endothelial function and vascular reactivity) mimic those achieved through exercise training. Therefore, the Company is exploring the potential of developing a protocol in which repeated, noninvasive ischemic conditioning treatments can be used to improve athletic performance. Research studies have suggested that repeated ischemic conditioning treatments could improve the rate of oxygen consumption by muscles, slow the rate of lactate build-up, and improve endurance.

Sports Boost™ will be a simple device that can be used at home or “on the road”. The device will include a pulse oximetry PPG probe, so that improvement in the rate of oxygen consumption by muscle tissue can be monitored.



Prevention of chronic wounds and delayed healing in high-risk patients

Certain patient groups (e.g., diabetics, immunocompromised) are especially prone to poor wound healing. In these patients, surgical incisions and virtually any type of transcutaneous intervention that results in skin injury have a high potential to develop into a chronic, nonhealing wound. The Company is investigating the potential of utilizing ischemic conditioning prior to these anticipated procedures to bolster the body’s ability to quickly repair these wounds before they become chronic.