AZD1656 in Diabetic Patients Hospitalised With Suspected or Confirmed COVID-19 (ARCADIA)
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|ClinicalTrials.gov Identifier: NCT04516759|
Recruitment Status : Recruiting
First Posted : August 18, 2020
Last Update Posted : November 9, 2020
|Condition or disease||Intervention/treatment||Phase|
|Covid19||Drug: AZD1656 Other: Placebo||Phase 2|
The ARCADIA Trial will assess the safety and efficacy of AZD1656 in 150 patients with either Type 1 or Type 2 diabetes who have been hospitalised with COVID-19.
AZD1656 is a glucokinase (GK; hexokinase 4) activator which has been shown to reduce blood glucose for up to 4 months in humans. Diabetic patients admitted to hospital with COVID-19 often present with hyperglycaemia and are particularly vulnerable to progression to severe COVID-19. Treatment with AZD1656 (in addition to their usual care) may provide additional glucose control which could help improve clinical outcomes in both Type 1 and Type 2 diabetic populations.
In addition to its glucose lowering effect, AZD1656 may have additional benefits to COVID-19 patients via its effects on immune function. In many patients with severe COVID-19, an overreaction of the body's own immune system can cause severe problems including damage to the lungs and heart, which can lead to breathing problems necessitating intubation and ventilation. AZD1656 has been shown to activate the migration of T regulatory cells to sites of inflammation in preclinical experiments. This migration of Treg cells to inflamed tissue is crucial for their immune-modulatory function (Kishore et al (2017)). AZD1656 could enhance Treg migratory capacity and may prevent the development of cardiorespiratory complications observed in hospitalised patients with COVID-19, leading to lower requirements for oxygen therapy and assisted ventilation, and reduced incidences of pneumonia and acute respiratory distress syndrome (ARDS).
Diabetic patients hospitalised with COVID-19 will be randomised to receive either AZD1656 tablets or placebo tablets on a 1:1 basis until they are discharged from hospital or until they require intubation/mechanical ventilation. The aim of the study is to determine whether AZD1656 improves clinical outcomes in diabetic patients hospitalised with COVID-19. The World Health Organization (WHO) 8-point Ordinal Scale for Clinical Improvement will be used as the standard methodology for measuring patient outcomes.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||150 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||This is a randomised double-blind study. Eligible patients will be randomly assigned to one of two groups (AZD1656 plus usual care or placebo plus usual care) on a 1:1 basis|
|Masking:||Double (Participant, Investigator)|
|Official Title:||A Phase II, Randomised, Double-blind, Placebo-controlled Clinical Trial to Assess the Safety and Efficacy of AZD1656 in Diabetic Patients Hospitalised With Suspected or Confirmed COVID-19|
|Actual Study Start Date :||August 12, 2020|
|Estimated Primary Completion Date :||March 2021|
|Estimated Study Completion Date :||March 2021|
Experimental: AZD1656 (plus Usual Hospital Care)
50mg film-coated tablets at a dose of 100mg BID
50mg film-coated tablets (at daily dose of 100mg BID)
Placebo Comparator: Matched Placebo (plus Usual Hospital Care)
Matched placebo tablets
Matched placebo tablets
- Clinical Improvement by Day 14 [ Time Frame: Day 1 to Day 14 ]Clinical Improvement measured as the percentage of subjects at Day 14 who are in categories 1-3 according to the WHO 8-point Ordinal Scale for Clinical Improvement, comparing AZD1656 treatment to placebo
- *Title: Clinical Improvement at Day 7, 14 and 21 [ Time Frame: Day 1 to Day 21 ]Clinical Improvement measured as the percentage of patients categorised at each severity rating on the WHO 8-point Ordinal Scale at Day 7, Day 14 and Day 21 versus baseline, comparing AZD1656 treatment with placebo.
- Glycaemic Control [ Time Frame: Day 1 to Day 21 ]Degree of glycaemic control as measured by the need to increase baseline medication requirements or the need to add additional diabetic medications to maintain appropriate blood glucose levels in patients receiving AZD1656 compared with placebo
- Occurrence of Adverse Events [ Time Frame: Day 1 to Day 28 ]Proportion of Treatment Emergent Adverse Events (TEAEs) leading to study drug discontinuation in patients receiving AZD1656 compared with placebo
- Occurrence of Serious Adverse Events [ Time Frame: Day 1 to Day 28 ]Proportion of Serious Adverse Events (SAEs) in patients receiving AZD1656 compared with placebo
- Duration of Hospitalisation [ Time Frame: Day 1 to Day 21 ]Time from hospital admission to hospital discharge (in hours) in patients receiving AZD1656 compared with placebo
- Time to Intubation/ Mechanical Intervention [ Time Frame: Day 1 to Day 21 ]Time from hospital admission to receiving intubation/mechanical ventilation in patients receiving AZD1656 compared with placebo
- Mortality Rate [ Time Frame: Day 1 to Day 28 ]Mortality rate in patients receiving AZD1656 compared with placebo.
- Pharmacokinetic Analysis [ Time Frame: Day 1 to Day 7 ]Plasma AZD1656 levels during first 7 days of treatment in patients receiving AZD1656 compared with placebo.
- Immunophenotyping Analysis [ Time Frame: Day 1 to Day 21 ]Immunophenotyping panel to be conducted by Flow Cytometry: between group comparison (AZD1656 versus placebo)
- Immunochemistry Analysis [ Time Frame: Day 1 to Day 21 ]Immunochemistry panel to be conducted using the Meso Scale Discovery (MSD) U-Plex multiplex assay.
- Cardiac Injury [ Time Frame: Day 1 to Day 21 ]Measurement of hsTroponin and NTproBNP to determine extent of cardiac injury in patients receiving AZD1656 compared with placebo
- Correlation of clinical outcomes with pre-treatment vitamin D levels (by measurement of 25-hydroxyvitamin D levels). [ Time Frame: Day 1 to Day 21 ]Measurement of 25-hydroxyvitamin D levels before treatment to determine whether there is any correlation between baseline vitamin D level and clinical improvement in patients treated with AZD1656 versus placebo.
- Correlation of patient ethnicity with clinical improvement [ Time Frame: Day 1 to Day 21 ]Sub group analysis of patient ethnicity, to determine whether there is any correlation between patient ethnicity and clinical improvement in patients treated with AZD1656 versus placebo.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04516759
|Contact: Mike Johnson||+44 (0)email@example.com|
|Barnsley Hospital NHS Foundation Trust||Recruiting|
|Barnsley, United Kingdom|
|Bradford Teaching Hospitals NHS Foundation Trust||Recruiting|
|Bradford, United Kingdom, BD9 6RJ|
|North Bristol NHS Trust||Recruiting|
|Bristol, United Kingdom, BS10 5NB|
|The Dudley Group NHS Foundation Trust||Recruiting|
|Dudley, United Kingdom, DY1 2HQ|
|Medway NHS Foundation Trust||Recruiting|
|Gillingham, United Kingdom, ME7 5NY|
|Hull & East Yorkshire NHS Trust||Recruiting|
|Hull, United Kingdom|
|Barts Health NHS Trust||Recruiting|
|London, United Kingdom, E1 1FR|
|Royal Free London NHS Foundation Trust||Not yet recruiting|
|London, United Kingdom, NW3 2QG|
|Penine Acute Hospitals NHS Trust||Recruiting|
|Salford, United Kingdom, M6 8HD|
|Sheffield Hospitals NHS Foundation Trust||Recruiting|
|Sheffield, United Kingdom, S10 2SB|
|Somerset NHS Foundation Trust||Recruiting|
|Taunton, United Kingdom, TA1 5DA|
|Walsall Healthcare NHS Trust||Recruiting|
|Walsall, United Kingdom, WS2 9PS|
|Principal Investigator:||Kieran McCafferty, MD||Barts & The London NHS Trust|