Those Receiving & Working in Dialysis at Risk for Infection ADVANCE (blog) Those of us who work in acute care hospitals shouldn't forget the large number of people being cared for in outpatient, ambulatory settings. Some of these centers also carry a significant risk for a healthcare acquired infection. I'm specifically thinking.

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With half a decade of treatment-resistant hypertension behind him, Cincinnati pediatrician Bill Thistlethwaite, 64, enrolled in a clinical trial evaluating renal nerve ablation as a way to curtail his high blood pressure.

It's been about a month since the minimally invasive procedure, and Thistlethwaite has not seen a significant drop in blood pressure, Dean Kereiakes, MD, a co-principal investigator of the trial at Cincinnati's Christ Hospital Heart and Vascular Center in Cincinnati told MedPage Today.

That doesn't necessarily mean the treatment isn't working because Thistlethwaite could be in the sham treatment arm of the randomized single-blind Symplicity HTN-3 pivotal trial.

In addition, previous studies have shown that initial nonresponders to the therapy can have a delayed response, generally defined as a reduction in systolic blood pressure of 10 mmHg or more.

In the nonrandomized Symplicity HTN-1 trial, the percentage of responders increased over time, reported Paul A. Sobotka, MD, from Ohio State University in Columbus, at the 2012 American College of Cardiology meeting. At 1 month, 69% of 143 patients responded; at 12 months, it was 79% of 130 patients; at 2 years, it was 90% of 59 patients; and at 3 years, 100% of 24 patients followed for 36 months responded.

The Symplicity HTN-3 trial will enroll more than 500 patients from 90 sites in a 2:1 ratio to bilateral renal artery denervation or a sham treatment. Only patients with arteries at least 3 mm in diameter and at least 20 mm in length will be enrolled and patients with multiple renal arteries are excluded.

When Enough is Enough

When Thistlethwaite was first referred to The Christ Hospital, Kereiakes made several attempts to get his blood pressure under control, but without success. Thistlethwaite then agreed to participate in the trial.

"One thing I like about this trial is that patients in the control arm can cross over at 6 months to treatment if they qualify," Kereiakes said. "It will require another procedure, but that is the only option we have in the U.S. right now."

The Symplicity Renal Denervation radiofrequency (RF) single-electrode probe from Medtronic, which is sponsoring the trial, is currently not approved for use in the U.S.

The procedure involves threading a catheter through the groin to the renal arteries. Radiofrequency energy is applied to disrupt the sympathetic nerve pathways that lie within the renal artery walls. The procedure generally takes under an hour to complete and patients could feasibly go home afterwards, but for the trial they are required to spend the night in the hospital.

Although Thistlethwaite was the first patient to be enrolled in the trial at Cincinnati center, he was among 100-plus patients screened for enrollment.

"The bar has been set very high for inclusion," Kereiakes said. "Patients must have a documented systolic blood pressure of 160 mmHg or greater for three measurements on the first screening. Their uncontrolled blood pressure must then be confirmed on 24-hour ambulatory monitoring."

In addition, patients must be taking at least three antihypertensive medications, with one being a diuretic, and they must achieve their blood pressure inclusion criteria on the maximum tolerated dose. Reasons for not achieving it on the maximum tolerated dose must be documented, Kereiakes said.

"It can be frustrating sometimes," he said, "because patients miss the mark in one screening with a reading of 155 mmHg and they're on five blood pressure medications, but they can't get into the trial."

Personally, Kereiakes would have set the limit at 150 mmHg, which would have enabled more people to potentially get treatment. "Even a 10-point drop from 150 to 140 mmHg translates into a 30% relative reduction in the risk of stroke over a decade," he said.

"We face a dilemma," he said. "Do we leave these patients on their five medications or do we scale back on a few drugs so their pressure goes up temporarily and they qualify for the trial?"

Thislethwaite has the advantage of being a clinician as well as a patient, so MedPage Today,asked him about cutting back on medications to qualify for the trial. If it were his decision, Thistlethwaite said he would take a patient off one or two drugs to assure eligibility.

"That's a powerful statement made by a physician-patient," Kereiakes said. "In a way, he has the patients' best long-term interest at heart."

Where It All Began

About 10 years ago, Thistlethwaite said he began to have some issues with type 2 diabetes and he had a stent implanted for unstable angina.

It's only been in the last 5 years that his internist has prescribed more and more blood pressure medication to bring his BP under better control. He has not, however, had any of the typical symptoms associated with high blood pressure, such as shortness of breath with exertion or headaches, "which is not uncommon," Kereiakes said. "After all, hypertension is called the silent killer."

In the Symplicity HTN-3 trial, the goal is not to see how many medications patients can eliminate. In fact, medications are to be kept the same unless a patient's blood pressure falls too low, at which point either the dose can be reduced or a medication stopped.

The biggest complication risk during renal artery denervation is injury to the renal artery, such as dissection or a tear, Kereiakes said. Vascular access site bleeds are a risk, as is renal artery stenosis, "which hasn't materialized in studies following patients for 2 years," he said.

Other denervation systems being tested include multi-electrode RF probes, balloon catheter RF probes, and probes that use ultrasonic energy. There also is research into using drugs that seep into the renal arterial wall where they have a neurotoxic effect.

After 6 months of active enrollment, the trial has nearly 50 people enrolled, three of them at Christ Hospital. Kereiakes expects end up with between five and ten patients, "which is like giving birth to barbed wire," he said referring to the slow enrollment relative to the number of patients screened.

The Symplicity HTN-3 trial is sponsored by Medtronic.

Kereiakes reported receiving research and grant support from Medtronic.

From the American Heart Association:

• Resistant Hypertension: Diagnosis, Evaluation, and Treatment

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Chris Kaiser

Cardiology Editor

Chris has written and edited for medical publications for more than 15 years. As the news editor for a United Business Media journal, he was awarded Best News Section. He has a B.A. from La Salle University and an M.A. from Villanova University. Chris is based outside of Philadelphia and is also involved with the theater as a writer, director, and occasional actor.

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