Novel Trial Design: CHIEF-HF

John A Spertus, Mary C Birmingham, Javed Butler, Ildiko Lingvay, David E Lanfear, Antonio Abbate, Mikhail L Kosiborod, Christina Fawcett, Paul Burton, C V Damaraju, James L Januzzi, John Whang, John A Spertus, Mary C Birmingham, Javed Butler, Ildiko Lingvay, David E Lanfear, Antonio Abbate, Mikhail L Kosiborod, Christina Fawcett, Paul Burton, C V Damaraju, James L Januzzi, John Whang

Abstract

Background: The expense of clinical trials mandates new strategies to efficiently generate evidence and test novel therapies. In this context, we designed a decentralized, patient-centered randomized clinical trial leveraging mobile technologies, rather than in-person site visits, to test the efficacy of 12 weeks of canagliflozin for the treatment of heart failure, regardless of ejection fraction or diabetes status, on the reduction of heart failure symptoms.

Methods: One thousand nine hundred patients will be enrolled with a medical record-confirmed diagnosis of heart failure, stratified by reduced (≤40%) or preserved (>40%) ejection fraction and randomized 1:1 to 100 mg daily of canagliflozin or matching placebo. The primary outcome will be the 12-week change in the total symptom score of the Kansas City Cardiomyopathy Questionnaire. Secondary outcomes will be daily step count and other scales of the Kansas City Cardiomyopathy Questionnaire.

Results: The trial is currently enrolling, even in the era of the coronavirus disease 2019 (COVID-19) pandemic.

Conclusions: CHIEF-HF (Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure) is deploying a novel model of conducting a decentralized, patient-centered, randomized clinical trial for a new indication for canagliflozin to improve the symptoms of patients with heart failure. It can model a new method for more cost-effectively testing the efficacy of treatments using mobile technologies with patient-reported outcomes as the primary clinical end point of the trial. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04252287.

Keywords: COVID-19; Kansas City Cardiomyopathy Questionnaire; canagliflozin; cardiomyopathy; heart failure.

Figures

Figure 1.
Figure 1.
Overview of study infrastructure. (1) At the center of the trial is the participant, who is offered participation by their provider/health network and opts in after learning more on a central recruitment website. (2) Once their eligibility is verified by their health network, they interact with the Mobile Health Platform (mHP) to eConsent and complete a baseline KCCQ. (3)Upon KCCQ score review for eligibility, the participant is randomized through an Interactive Response Technology (IRT) system, which triggers direct-to-patient drug delivery. (4) The participant is also be shipped a Welcome Kit, including the Fitbit, from the Virtual Coordinating Center, which serves as participant liaison throughout the study for technology set-up and troubleshooting, call center support, safety reporting, and compliance monitoring. (5) All patient source data (ePROs, medication diaries) are collected via the mHP study app and Fitbit. (6) Upon consent and randomization, a token will be applied to patients to collect medical and prescription insurance claims. (7) All data will be integrated in and normalized within the PRA data cloud and translated into Study Data Tabulation Model (SDTM) data sets for analysis and submission to the FDA. IRT indicates Interactive Response Technology.
Figure 2.
Figure 2.
Sample screenshots of data collection app. KCCQ indicates Kansas City Cardiomyopathy Questionnaire. PGIs, Patient Global Impression - Severity
Figure 3.
Figure 3.
Overview of study design. HFpEF indicates heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; and KCCQ, Kansas City Cardiomyopathy Questionnaire.

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