Dr. Maria Ali, CMO, and Meg Jardine, MBBS, Associate Professor at the University of New South Wales and member of the CREDENCE steering committee, discuss the results and implications of the CREDENCE trial.

Associate Professor Meg Jardine

Meg Jardine


Maria: As a physician, you’ve chosen to focus on research. Why is research like CREDENCE so important for healthcare in general and, in the case of CREDENCE, for nephrology?

Meg: I decided to specialize in nephrology because I saw an unmet need in a group of patients with a huge clinical burden. Research became my focus because that’s where you can make the most impact. Now I spend most of my time in research with people with chronic diseases trying to prevent progression and complications of those diseases. I’m particularly interested in trials because that’s the most rigorous way to find new treatments.

Let me add, however, that research should not end with trials. I am a firm believer in the concept of a learning health system—and what that means is research needs to be embedded in every step of health care—every aspect of what we do should ideally be evaluated with research. For example, we need to be researching ways to best implement the things we learn in trials into clinical practice. Actually kidney disease is a prime example of that gap. Even though angiotensin medications were developed nearly two decades ago, we find in survey after survey that many patients aren’t getting these drugs. So, relating back to CREDENCE—which has now proven a new frontier in chronic disease treatment—we don’t want to wait 5–10 years for the benefits to be fully implemented into health practice. For that to happen, we need to research better implementation practices.

As for CREDENCE, it’s a once-in-a-generation result for the treatment of kidney disease and more. Kidney disease affects nearly every parameter of your health, and it’s slow and progressive. Kidney disease was really in the desert waiting for new treatments. We’ve had the renin-angiotensin blockers but no new treatments to stop the progression of kidney disease and prevent dialysis for nearly two decades. Now, CREDENCE has shown the SGLT2 inhibitor Canagliflozin reduces kidney disease progression by around one third. CREDENCE even showed a reduced need for dialysis and transplantation. This is significant, because there’s been no other study that’s shown you can prevent dialysis. That’s a transformational result.

We’re also getting equally exciting news from the SGLT2 inhibitor trials for cardiovascular results. This class of medications has profound implications in multiple areas, and the magnitude of benefit is often better than anything that’s gone before. It’s hugely exciting and represents hope for millions of patients. I don’t think five years ago anyone expected the benefits would be this strong. Once again, it shows the importance of high-quality trials.

 

Maria: How do you achieve success in a large global trial like CREDENCE?

Meg: It’s certainly not by accident. We had 690 sites in 34 countries representing a huge workforce. The most important element to success is having a really connected team with a unified health purpose that stays engaged with the science throughout the trial. Our medical and scientific leadership maintained open communication with our investigators and coordinators throughout the trial. Our discussions were focused on the science of this trial and of the field. With so many individual national characteristics and viewpoints from different kinds of practitioners, we shared a lot of unique insights into what the problem was and why we thought SGLT2 inhibitors might help. The result of all these discussions was we had a really engaged team.

 

Maria: How would you rate the success of CREDENCE? Is there something that could have been done better?

Meg: Actually, on every metric, this trial did well. It recruited to time, which is not always the case. We were able to find a great group of patients who were willing to commit to the study – without them, we wouldn’t have found this great treatment that will benefit thousands and thousands around the world. The staff involved in this trial were unified in their purpose and stayed focused on answering the scientific question. They looked after the participants all through the study.

The next step for us as a clinical community is to get this treatment to the patients. We are interested in ongoing engagement with the community and translating this research into implementation. Part of that is helping physicians and patients understand how to use this medication. There are always many barriers to getting a new treatment into clinical practice but that’s the next challenge with this new class of drugs that have proven to have such great benefits for potentially millions of people around the world.

 

Meg Jardine will be presenting at the upcoming ASN Conference in Washington, D.C.:

Session: Diabetic Kidney Disease VI. New Approaches to Prevention and Treatment
Presentation: SGLT-2 Inhibition for DKD
Nov. 6th, 2:30 PM, 150, Walter E. Washington Convention Center

 

Poster Session: TH-PO1202 – Canagliflozin slows declines in kidney function in people with baseline eGFR
Presentation: Late-Breaking Clinical Trials
Nov. 7th, 10:00 AM, Exhibit Hall, Walter E. Washington Convention Center

 

Poster  Session: TH-PO1204 – Impact of Canagliflozin on eGFR slope in people with optimized glucose control: randomized analyses from CREDENCE
Presentation: Late-Breaking Clinical Trials
Nov 7th, 10:00 AM, Exhibit Hall, Walter E. Washington Convention Center

 

Session: CREDENCE
Presentation: Major Clinical Trials for Diabetic Kidney Disease: CREDENCE and SONAR
Nov. 8th, 10:30 AM, Hall D, Walter E. Washington Convention Center

 

Session: Renal, Cardiovascular, and Safety Outcomes of Canagliflozin According to Baseline Kidney Function: A CREDENCE Secondary Analysis
Presentation: Moving the Needle for Treatment of Diabetic Kidney Disease (OR0602-2)
Nov. 9th, 4:30 PM, Ballroom C, Walter E. Washington Convention Center