ARCADIA study protocol: a phase II, randomised, double-blind, placebo-controlled clinical trial to assess the safety and efficacy of AZD1656 in patients with diabetes hospitalised with suspected or confirmed COVID-19

Abstract

Introduction: COVID-19, caused by SARS-CoV-2, remains a global pandemic that has affected more than 100 million people worldwide with over 4.8 million deaths as of October 2021. Patients with diabetes have both an increased susceptibility to SARS-CoV-2 infection, enhanced disease severity and increased risk of mortality. The challenge presented in these patients is both to improve glycaemic control-which itself may confer a survival advantage-and to help maintain or restore immunological homeostasis. The specific glucokinase activator AZD1656 may address both of these challenges via its glucose-lowering effect and its immunological mechanism of action. The aim of the Alleviation of cardioRespiratory complications in patients with COVID-19 And DIAbetes (ARCADIA) trial is to investigate this hypothesis and determine whether AZD1656 can improve clinical outcomes for these patients.

Methods and analysis: ARCADIA is a double-blind, placebo-controlled, interventional study of AZD1656 in 150 patients with either type 1 or type 2 diabetes who have been admitted to hospital with COVID-19. Eligible, consented patients will be randomised in a 1:1 manner to receive either active drug or matched placebo tablets while they are in hospital. All patients will receive the usual and current standard of care for patients with COVID-19 in that hospital. Clinical and laboratory data will be collected and assessed at baseline and throughout their participation in the study. Data will be captured in the case report form, which will be electronically archived at the end of the trial in the trial master file. The WHO 8-point Ordinal Scale for Clinical Improvement will be used to measure clinical outcome for the primary endpoint of the trial.

Ethics and dissemination: Ethical approval has been obtained from the East Midlands-Leicester South Ethics Committee (REC 20/EM/0198) in the UK, from the National Bioethics Committee of Medicines and Medical Devices in Bucharest, Romania, and from the Ethics Committee IKEM a TN in Prague, Czech Republic. All study-related data will be used by the sponsor in accordance with local data protection law. In the UK, all patient identifiable data will be stored on a password-protected National Health Service N3 network with full audit trail. Anonymised data will be stored in an ISO27001 certificated data warehouse.

Trial registration number: EudraCT 2020-002211-21, NCT04516759.

Keywords: COVID-19; clinical trials; general diabetes.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

WHO Ordinal Scale for Clinical Improvement (COVID-19 trials, 18 February 2020). ECMO, Extracorporeal membrane oxygenation; RRT, Renal Replacement Therapy.

Figure 2

Study design. *Day 28 or day study end criteria are met.