A Medical Device Daily

Data from a multi-center registry of targeted renal therapy (TRT) in patients at high risk for contrast-induced nephropathy (CIN) — described as a cause of kidney failure and a large unmet need — were presented at the 32nd Annual Scientific Meeting of the Society of Interventional Radiology (SIR; Fairfax, Virginia) in Seattle by Bret Wiechmann, MD, a vascular and interventional radiologist at Vascular and Interventional Physicians, North Florida Regional Medical Center (Gainesville).

TRT is the delivery of therapeutic agents to the kidneys via the renal arteries through the Benephit Infusion Catheter System made by FlowMedica (Fremont, California).

TRT may offer benefit in direct infusion of therapeutic levels of medications without the side effects that can be encountered with conventional IV delivery, according to SIR.

Wiechmann’s presentation, “Targeted Renal Therapy for the Prevention of Contrast-Induced Nephropathy [CIN],” included analysis of 366 patients enrolled in the Benephit System Renal Infusion Therapy (Be-RITe!) international registry being conducted at 16 institutions worldwide.

CIN is an increase in serum creatinine which damages the kidneys. A rise in creatinine levels may indicate that the kidneys are not functioning well. Normal levels of creatinine in the blood range from 0.5 to 1.11 mg/dL.

The Be-RITe! Registry is intended to capture “real world” use, device performance characteristics, clinical outcomes and adverse events data associated with the delivery of TRT with either the Benephit CV (cardiovascular) or Benephit PV (peripheral vascular) Infusion Systems. Both systems have received clearance for the infusion of physician-specified agents in the peripheral vasculature including but not limited to the renal arteries.

Wiechmann reported that the renal arteries were accessed bilaterally with the Benephit catheter with a mean time of two minutes in 94% of patients. There were a total of four (1.1%) reported complications, all resolved without lasting adverse effects.

Agents infused using TRT included: fenoldopam mesylate (92.5% of patients), sodium bicarbonate (4.7%), alprostadil (2.8%) and nesiritide (0.6%).

A sub-set analysis of the registry population was completed on 189 patients who had available SCr (serum creatinine) follow-up at 48 hours after the intra-renal infusion of fenoldopam mesylate during coronary or peripheral intervention and/or diagnostics. Based on a model for predicting the incidence of CIN, published by Mehran et al. in the Journal of the American College of Cardiology, 30.6% of the 189 patients in the registry population would be expected to develop CIN.

“Yet 9.4% of the 189 patients who received an intra-renal infusion of fenoldopam developed CIN, an estimated 69% reduction in relative risk when compared to the predicted incidence of CIN in the same population,” Wiechmann said.

Major risk factors for the patients evaluated in the sub-set analysis included: high incidence of diabetes (60.7%); high average volume of contrast dye (155.3 mL), low average creatinine clearance (37.1 mL/min) and high serum creatinine (2.1 mg/dL). “Patients in our registry were at very high risk, with some having three or more risk factors, yet fewer than one in 10 developed CIN,” Wiechmann said. “Further studies are needed to support these results.”

A randomized, placebo-controlled clinical trial to evaluate the efficacy of TRT with fenoldopam to prevent CIN is currently being designed and organized. It is anticipated that SIR, with the Cooperative Alliance for Interventional Radiology Research (CAIRR) involved in the trial.

FlowMedica’s initial solutions for TRT — the Benephit Infusion Systems — have received 510(k) clearance and CE marking for the infusion of physician-specified agents in the peripheral vasculature including, but not limited to, the renal arteries.

The company’s products have not received FDA clearance to treat CIN or any other condition

In other reports from the meeting:

CELSION (Columbia, Maryland) reported that Sergio Dromi, MD, a research fellow in the Diagnostic Radiology Department of the Clinical Center at the National Institutes of Health presented data on Pulsed-High Intensity Focused Ultrasound (HIFU) enhanced delivery of tissue levels of doxorubicin and resultant tumor growth inhibition when using heat-sensitive liposomes encapsulating doxorubicin (ThermoDox).

The study used Celsion’s Prolieve Thermodilatation system, a minimally invasive transurethral microwave system which combines a transurethral microwave thermotherapy device with pressure applied by a balloon catheter.

Michael Tardugno, Celsion’s president/CEO, said that the study demonstrated the ability of the company’s heat-activated liposome to deliver high levels of anticancer drugs to tumor tissue. With this HIFU-based study, in addition to our on-going studies using radiofrequency ablation and microwave energy, we have further demonstrated that ThermoDox is indifferent to the heating medium triggering the drug release.”

He added: “NIH and Celsion are collaborating on a number of pre-clinical and clinical projects. These results further underscore the utility and versatility of our platform technology. This work will be used to refine tumor targeting and ultimately to improve the efficacy of drugs using our heat activated delivery system.”

Prolieve is marketed, in the U.S., under a distribution agreement with Boston Scientific (Natick, Massachusetts).

The study was conducted under the leadership of Steven Libutti, MD, of the Surgery Branch of the National Cancer Institute, with Brad Wood, MD, and Victor Frenkel, PhD, of the Diagnostic Radiology Department & Molecular Imaging Laboratory of the NIH Cancer Center.