The CHIEF-HF trial, a randomized placebo-controlled study that was conducted remotely without in-person interactions between doctors and patients, successfully demonstrated that the sodium–glucose cotransporter 2 (SGLT2) inhibitor canagliflozin significantly reduces symptom burden in patients with heart failure (HF). This novel trial design could improve the way in which clinical studies are conducted in the future, by reducing costs and by increasing the speed of data acquisition.

“At the time this trial was designed, there was limited information on the health status benefits of the SGLT2 inhibitors in patients with HF,” explains John Spertus, first author of the study. “We thus worked with Janssen to design a clinical trial without any face-to-face visits to simplify the process of participating in a clinical trial for patients,” he adds.

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Given the recent qualification of the Kansas City Cardiomyopathy Questionnaire (KCCQ) by the FDA as a clinical outcome assessment and the fact that KCCQ data can be collected using smartphones, the CHIEF-HF trial investigators sought to conduct a completely decentralized virtual study to evaluate whether canagliflozin improves symptom burden in patients with HF. In total, 476 participants with HF were randomly assigned to canagliflozin (100 mg daily) or placebo. The participants provided informed consent via a mobile phone app, and the study drug and wearable activity monitor were shipped directly to their homes. Patients were asked to report the number of days that they took the study drug via the app, and they completed the KCCQ over the 12-week treatment period. The patients’ symptom reports were assessed at weeks 2, 4, 6 and 12 after initiation of the drug.

At 12 weeks, the improvement in KCCQ total symptom score was significantly greater in canagliflozin-treated patients than in placebo-treated patients. The reduction in symptom burden with canagliflozin was consistent across the range of ejection fraction and in patients with or without diabetes mellitus. Of note, the difference in KCCQ total symptom score between the treatment groups was apparent as early as 2 weeks after starting drug therapy.

This novel trial design could improve the way in which clinical studies are conducted in the future, by reducing costs and by increasing the speed of data acquisition

Importantly, this trial was initiated 2 weeks before a US national shutdown related to the COVID-19 pandemic. “The decentralized and completely virtual nature of this trial exemplifies how novel strategies for trial implementation might be helpful in circumstances in which traditional trials are difficult to conduct, such as during the COVID-19 pandemic,” comments Prakriti Gaba (Brigham and Women’s Hospital, USA), who was not involved in the study. “Moreover, the investigators noted greater generalizability by enrolling a higher number of women and minorities, a longstanding limitation of traditional clinical trials,” she adds.