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VA comparison of two 'water pills' will use new clinical-trial approach

January 26, 2016

Dr. Frank Lederle is chairing a VA
Dr. Frank Lederle is chairing a VA "point of care" study comparing two diuretics. (Photo by April Eilers)

Dr. Frank Lederle is chairing a VA "point of care" study comparing two diuretics. (Photo by April Eilers)

VA is launching a clinical trial comparing two diuretics—medications that get rid of excess water in the body by increasing urine flow. The drugs, also known as "water pills," can help lower blood pressure in people with hypertension.

Nothing revolutionary there. In fact, each of the drugs has been around for decades.

What is new is the way the trial is being run.

The study is one of the first examples in VA of "point of care" research. It's an innovative model that experts say is more cost-effective than conventional clinical trials. And the results, they say, are easier to translate into everyday care.

"We are using a new, efficient, less expensive study design," says study chair Dr. Frank Lederle, a physician at the Minneapolis VA Health Care System and an investigator with VA's Center for Chronic Disease Outcomes Research. "All patient care, including the study drug, will be managed by the Veteran's regular primary care provider. It's a clinically integrated design."

"The trial is run entirely from a central headquarters, which is why we expect such a dramatic reduction in cost."

Lederle is also a professor at the University of Minnesota School of Medicine.

Leading the study with him is Dr. William Cushman, a well-known hypertension expert with the Memphis VA Medical Center and the University of Tennessee Health Science Center.

The trial will get underway in Boston in March 2016 and then be rolled out to a handful of other VA sites: Minneapolis, Memphis, Houston, Cleveland, and West Los Angeles. More sites may be added as the study progresses.

No need for on-site research personnel

The key to the cost-savings, says Lederle, is that no special research personnel are required at any of the study sites.

"The most exciting part to a trialist is that there are no local research personnel," he says. "The trial is run entirely from a central headquarters, which is why we expect such a dramatic reduction in cost."

The two drugs being compared are both thiazides. These drugs act on the kidneys to remove more salt and water from the body through urination. This relaxes blood pressure walls and lowers blood pressure.

More than a million VA patients are prescribed such drugs each year. The great majority—more than 95 percent—get hydrochlorothiazide. Only about 2 or 3 percent get chlorthalidone, which costs about the same. But indirect evidence suggests the less commonly used drug—chlorthalidone—may actually do a better job of preventing stroke, heart attack, and other life-threatening cardiovascular events.

Lederle coauthored a 2014 editorial in the American Journal of Kidney Disease that reviewed the evidence and stressed "the urgent need for a comparative efficacy outcome trial" pitting the two diuretics head to head.

The new VA study will do just that. It aims to enroll 13,500 Veterans over three years. All the participants are age 65 or older, and all are currently taking hydrochlorothiazide.

About half the Veterans will be randomly assigned to continue taking hydrochlorothiazide. The others will be switched to an equivalent dose of chlorthalidone. The study team will follow the Veterans for three years, on average, to track their cardiovascular and mortality outcomes.

Study conducted within framework of routine care

Unlike most clinical trials, the entire protocol will be conducted within the framework of routine care. VA primary care providers will see an alert in the records of patients who meet the eligibility guidelines for the study. The provider can read about the study and decide whether to allow the research team to contact the patient. Patients who agree to take part and who complete informed-consent paperwork are then randomized to one drug or the other.

At this point, care returns to the regular provider. He or she will see orders for the assigned treatment in the electronic medical record, and prescribe accordingly.

"There's very little disruption in the patient's care," notes Lederle.

The research team will use the electronic medical record and other databases to passively track clinical outcomes. They'll also collect data on deviations from treatment protocols, and patient compliance with the assigned treatment. As far as patients are concerned, there are no research interviews, surveys, or study visits to deal with. Just routine care.

Lederle says the point-of-care design, still relatively new, is likely to become more common in clinical research over the next few years. "We expect it will not only lower costs significantly, but that the study results will be available much sooner to help guide clinical practice."


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