The Effect of Multi-Parametric Magnetic Resonance Imaging in Standard of Care for Nonalcoholic Fatty Liver Disease: Protocol for a Randomized Control Trial

Dimitar Tonev, Elizabeth Shumbayawonda, Louise Ann Tetlow, Laura Herdman, Marika French, Soubera Rymell, Helena Thomaides-Brears, Filipe Caseiro-Alves, Miguel Castelo-Branco, Carlos Ferreira, Minneke Coenraad, Hildo Lamb, Meinrad Beer, Matt Kelly, Rajarshi Banerjee, Matthias Dollinger, RADIcAL1, Neelam Hassanali, Rexford Newbould, Lucy Walker, Dimitar Tonev, Elizabeth Shumbayawonda, Louise Ann Tetlow, Laura Herdman, Marika French, Soubera Rymell, Helena Thomaides-Brears, Filipe Caseiro-Alves, Miguel Castelo-Branco, Carlos Ferreira, Minneke Coenraad, Hildo Lamb, Meinrad Beer, Matt Kelly, Rajarshi Banerjee, Matthias Dollinger, RADIcAL1, Neelam Hassanali, Rexford Newbould, Lucy Walker

Abstract

Background: The rising prevalence of nonalcoholic fatty liver disease (NAFLD) and the more aggressive subtype, nonalcoholic steatohepatitis (NASH), is a global public health concern. Left untreated, NAFLD/NASH can lead to cirrhosis, liver failure, and death. The current standard for diagnosing and staging liver disease is a liver biopsy, which is costly, invasive, and carries risk for the patient. Therefore, there is a growing need for a reliable, feasible, and cost-effective, noninvasive diagnostic tool for these conditions. LiverMultiScan is one such promising tool that uses multi-parametric magnetic resonance imaging (mpMRI) to characterize liver tissue and to aid in the diagnosis and monitoring of liver diseases of various etiologies.

Objective: The primary objective of this trial (RADIcAL1) is to evaluate the cost-effectiveness of the introduction of LiverMultiScan as a standardized diagnostic test for liver disease in comparison to standard care for NAFLD, in different EU territories.

Methods: RADIcAL1 is a multi-center randomized control trial with 2 arms conducted in 4 European territories (13 sites, from across Germany, Netherlands, Portugal, and the United Kingdom). In total, 1072 adult patients with suspected fatty liver disease will be randomized to be treated according to the result of the mpMRI in the intervention arm, so that further diagnostic evaluation is recommended only when values for metrics of liver fat or fibro-inflammation are elevated. Patients in the control arm will be treated as per center guidelines for standard of care. The primary outcome for this trial is to compare the difference in the proportion of patients with suspected NAFLD incurring liver-related hospital consultations or liver biopsies between the study arms, from the date of randomization to the end of the study follow-up. Secondary outcomes include patient feedback from a patient satisfaction questionnaire, at baseline and all follow-up visits to the end of the study, and time, from randomization to diagnosis by the physician, as recorded at the final follow-up visit.

Results: This trial is currently open for recruitment. The anticipated completion date for the study is December 2020.

Conclusions: This randomized controlled trial will provide the evidence to accelerate decision making regarding the inclusion of mpMRI-based tools in existing NAFLD/NASH clinical care. RADIcAL1 is among the first and largest European health economic studies of imaging technologies for fatty liver disease. Strengths of the trial include a high-quality research design and an in-depth assessment of the implementation of the cost-effectiveness of the mpMRI diagnostic. If effective, the trial may highlight the health economic burden on tertiary-referral hepatology clinics imposed by unnecessary consultations and invasive diagnostic investigations, and demonstrate that including LiverMultiScan as a NAFLD diagnostic test may be cost-effective compared to liver-related hospital consultations or liver biopsies.

Trial registration: ClinicalTrials.gov NCT03289897 https://ichgcp.net/clinical-trials-registry/NCT03289897.

International registered report identifier (irrid): DERR1-10.2196/19189.

Keywords: NAFLD; NASH; biomarker; health economics; multiparametric MRI.

Conflict of interest statement

Conflicts of Interest: DT, ES, LAT, LH, MF, SR, HTB, CF, MK, and RB are affiliated with Perspectum Ltd. Perspectum Ltd is a privately funded commercial enterprise that develops medical devices to address unmet clinical needs, including LiverMultiScan. Perspectum Ltd is the sponsor of this study. MCB, FCA, MC, HL, MB, and MD have no conflicts of interest to declare.

©Dimitar Tonev, Elizabeth Shumbayawonda, Louise Ann Tetlow, Laura Herdman, Marika French, Soubera Rymell, Helena Thomaides-Brears, Filipe Caseiro-Alves, Miguel Castelo-Branco, Carlos Ferreira, Minneke Coenraad, Hildo Lamb, Meinrad Beer, Matt Kelly, Rajarshi Banerjee, Matthias Dollinger, RADIcAL1. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 26.10.2020.

Figures

Figure 1
Figure 1
Summary of study visits for participants in the RADIcAL1 clinical trial. m: months; PDFF: proton density fat fraction.
Figure 2
Figure 2
Sample reports that demonstrate the information that can be derived from the use of mpMRI to aid as a diagnostic tool for clinicians, highlighting the differences between a healthy patient with low cT1 and a patient with suspected nonalcoholic fatty liver disease (NAFLD) and high cT1. PDFF: proton density fat fraction.

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