AZD1656 in Diabetic Patients Hospitalised With Suspected or Confirmed COVID-19 (ARCADIA)
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|ClinicalTrials.gov Identifier: NCT04516759|
Recruitment Status : Completed
First Posted : August 18, 2020
Results First Posted : April 25, 2022
Last Update Posted : April 25, 2022
|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)|
|Actual Enrollment :||170 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|
|Actual Primary Completion Date :||April 25, 2021|
|Actual Study Completion Date :||May 12, 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 ]
The World Health Organization (WHO) 8-point Ordinal Scale for Clinical Improvement (OSCI) was used to measure Clinical Improvement at Day 14 versus baseline, comparing AZD1656 treatment with placebo. The WHO OSCI score ranges from 0-8 (0 = no symptoms, 8 = death). The higher the score the worse the condition of the patient.
Results are presented as number of responders. Patients who were assigned a WHO score of 1, 2 or 3 at Day 14 were considered a treatment responder. A patient who was discharged before Day 14 was also considered a responder. All other patients (WHO scores 4-8 at Day 14) were considered treatment failures.
- Clinical Improvement at Day 7, 14 and 21 [ Time Frame: Day 1 to Day 21 ]
The World Health Organization (WHO) 8-point Ordinal Scale for Clinical Improvement (OSCI) was used to measure Clinical Improvement at Day 7, Day 14 and Day 21 versus baseline, comparing AZD1656 treatment with placebo.
Results are presented as the percentage of patients categorised at each severity rating at each timepoint on the WHO 8-point OSCI scale.
The WHO OSCI score ranges from 0-8 (0 = no symptoms, 8 = death). The higher the score the worse the condition of the patient.
Study Drug Discontinuation was the date on which a patient discontinued treatment. Treatment was given for a maximum of 21 days, or until date of hospital discharge (WHO score 1 or 2), or date mechanical ventilation was required (WHO score 6 or 7) or until date of death (WHO score 8).
- 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
- Mortality Rate [ Time Frame: Day 1 to Day 28 ]Mortality rate in patients receiving AZD1656 compared with placebo.
- Intubation/Mechanical Ventilation [ Time Frame: Day 1 to Day 21 ]Number of Patients Receiving Intubation/Mechanical Ventilation
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
|Principal Investigator:||Kieran McCafferty, MD||Barts & The London NHS Trust|