CREDENCE Brings Together Multiple Groups in Successful Trial
Sun Kim, MD, MS, associate professor of endocrinology, was a principal investigator at Stanford for a recent randomized, placebo-controlled clinical trial of the drug canagliflozin, which is a sodium glucose co-transporter 2 inhibitor. This class of drug for Type 2 diabetes controls high blood sugar while lowering the risk of death from heart attack or stroke in patients who also have heart disease.
Canagliflozin was approved by the Food and Drug Administration based on the CANagliflozin cardioVascular Assessment Study, or CANVAS, which assessed the drug in patients with or at high risk of cardiovascular disease. Patients were excluded unless they had “almost normal kidneys,” according to Tara Chang, MD, associate professor of nephrology, who is director of clinical research for the division of nephrology.
Yet patients with Type 2 diabetes are at high risk for kidney disease, so testing the drug in diabetic patients with kidney disease became the aim of another clinical trial, CREDENCE (Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants with Diabetic Nephropathy).
“What made us so excited about CREDENCE was that we focused on people with advanced kidney disease,” says Chang. “CREDENCE was a sicker population than CANVAS with regard to kidney disease, and canagliflozin worked amazingly well.”
The primary composite end point of the study included end-stage kidney disease, doubling of serum creatinine, or renal or cardiovascular death. End-stage kidney disease was defined as needing dialysis, getting a kidney transplant, or having kidney function less than 15% of normal. In the end, says Chang, “People randomized to canagliflozin had a 30% lower rate of this primary outcome compared with patients who were randomized to placebo.”
That was a home run: The trial was ended early because of benefit, a rarity. It is the first trial in nearly 20 years to identify a therapy that slows progression to renal failure in patients with Type 2 diabetes.
A few years ago, says Kim, Stanford’s Department of Medicine participated in few clinical trials. “Stanford has a long history of strength in basic science research,” she explains, “and we have really great mechanistic and physiology studies. But we weren’t focusing much on clinical trials. The infrastructure to support clinical research was very cumbersome; just simple Institutional Review Board approval was very time-consuming.”
Then Ken Mahaffey, MD, professor of cardiovascular medicine, started up the Stanford Center for Clinical Research, and the department began to grow its participation in clinical trials. Kim mentions a few pain points that have eased in recent years: “Ken streamlined a lot of logistics and helped with operational aspects of the larger programs for grant and proposal submissions.”
Much of the reward of participating in CREDENCE for Kim was working with a team to design and conduct the trial, including other Stanford researchers with important roles: Mahaffey as the overall study co-principal investigator with Vlado Perkovic from Australia as well as Chang and Glenn Chertow, MD, MPH, professor of nephrology, as national leaders in the United States responsible for site recruitment and retention and data quality. Mahaffey also co-led and Chang was a member of the event adjudication committee.
Kim affectionately calls her partnership with Mahaffey and Chang the CKD (cardiology, kidney, diabetes) group. As a caregiver, she says, “It’s exciting to tell a patient that this drug can control glucose, and it has other benefits like helping the kidneys and the heart.”
The CREDENCE database is a rich one, and abstracts are already underway for upcoming meetings in endocrinology, nephrology, and cardiology to inform the medical community about the striking results.