ARCADIA: AZD1656 in Diabetic Patients Hospitalised With Suspected or Confirmed COVID-19

Sponsor
St George Street Capital (Other)
Overall Status
Completed
CT.gov ID
NCT04516759
Collaborator
(none)
170
30
2
9
5.7
0.6

Study Details

Study Description

Brief Summary

The ARCADIA Trial is a randomised, double-blind, placebo-controlled clinical trial to assess the safety and efficacy of AZD1656 in patients with either Type 1 or Type 2 diabetes, hospitalised with COVID-19.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

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 Design

Study Type:
Interventional
Actual Enrollment :
170 participants
Allocation:
Randomized
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 basisThis 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)
Primary Purpose:
Treatment
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 :
Aug 12, 2020
Actual Primary Completion Date :
Apr 25, 2021
Actual Study Completion Date :
May 12, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: AZD1656 (plus Usual Hospital Care)

50mg film-coated tablets at a dose of 100mg BID

Drug: AZD1656
50mg film-coated tablets (at daily dose of 100mg BID)

Placebo Comparator: Matched Placebo (plus Usual Hospital Care)

Matched placebo tablets

Other: Placebo
Matched placebo tablets

Outcome Measures

Primary Outcome Measures

  1. Clinical Improvement by Day 14 [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.

Secondary Outcome Measures

  1. Clinical Improvement at Day 7, 14 and 21 [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).

  2. Glycaemic Control [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

  3. Occurrence of Adverse Events [Day 1 to Day 28]

    Proportion of Treatment Emergent Adverse Events (TEAEs) leading to study drug discontinuation in patients receiving AZD1656 compared with placebo

  4. Occurrence of Serious Adverse Events [Day 1 to Day 28]

    Proportion of Serious Adverse Events (SAEs) in patients receiving AZD1656 compared with placebo

  5. Duration of Hospitalisation [Day 1 to Day 21]

    Time from hospital admission to hospital discharge (in hours) in patients receiving AZD1656 compared with placebo

  6. Mortality Rate [Day 1 to Day 28]

    Mortality rate in patients receiving AZD1656 compared with placebo.

  7. Intubation/Mechanical Ventilation [Day 1 to Day 21]

    Number of Patients Receiving Intubation/Mechanical Ventilation

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Male or Female.

  2. Aged 18 and older.

  3. Have either Type I or Type II Diabetes Mellitus.

  4. Hospitalised with suspected or confirmed novel coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)) infection at time of enrolment, categorised as stage 3, 4 or 5 on the WHO Ordinal Scale for Clinical Improvement.

  5. Blood glucose level at or above 4 mmol/L.

  6. Able to take oral (tablet) formulation of medication.

  7. Patient is able to provide written informed consent prior to initiation of any study procedures.

Exclusion Criteria:
  1. In the opinion of the clinical team, progression to intubation or mechanical ventilation is imminent and inevitable, within the next 24 hours, irrespective of the provision of treatments.

  2. Patients admitted with primary suspected or proven Mycoplasma pneumoniae, Chlamydia pneumoniae and bacterial pneumonia, who acquired COVID-19 while hospitalized.

  3. Treatment with immunomodulators or anti-rejection drugs within the last 3 months.

  4. Pregnant or breast feeding.

  5. Men, and women of child-bearing potential, unwilling to use highly effective contraception during their participation in the trial and for 2 weeks after study completion.

  6. Anticipated transfer to another hospital which is not a study site within 72 hours.

  7. Known sensitivity to any of the study medication/placebo excipients.

  8. Prior dosing with AZD1656 on a previous clinical trial.

  9. Patients admitted as a result of and receiving immediate treatment for an acute asthmatic attack, acute myocardial infarction, acute cerebrovascular event.

  10. Any known non-COVID-19, non-diabetes related, serious condition which, in the opinion of the clinical team, makes the patient unsuitable for the trial.

  11. Known history of drug or alcohol abuse within previous 12 months of screening.

  12. Known history of HIV, hepatitis C or unresolved hepatitis B or severe liver disease.

  13. Current or planned use of gemfibrozil or any other strong inhibitors of CYP2C8.

  14. Current or previous participation in another clinical trial where the patient has received a dose of an Investigational Medicinal Product (IMP) containing small molecule treatment(s) within 30 days or 5 half-lives (whichever is longer) prior to enrolment into this study, or containing biological treatment(s) within 3 months prior to entry into this study.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Masarykova Univerzita - Fakultni Nemocnice U SV Anny V Brne (308) Brno Czechia
2 Nemocnice Hořovice (309) Hořovice Czechia
3 Oblastni Nemocnice Kolín (306) Kolín Czechia
4 Klaudianova Nemonice (302) Mladá Boleslav Czechia
5 Fakultni Nemocnice V Motole (303) Prague Czechia
6 Thomayerova Nemonice (310) Prague Czechia
7 Nemocnice Třebíč (305) Třebíč Czechia
8 Colentina Clinical Hospital (204) Bucharest Romania
9 Spitalul Clinic de Boli Infectioase Cluj-Napoca (203) Cluj-Napoca Romania
10 Spitalul Clinic de Pneumoftiziologie "Leon Daniello" Cluj-Napoca (202) Cluj-Napoca Romania
11 Spitalul Clinic de Boli Infectioase Constanţa (207) Constanţa Romania
12 Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr Victor Babes Craiova (206) Craiova Romania
13 Spitalul Judetean de Urgenta Deva (208) Deva Romania
14 Spitalul Clinic de Boli Infectioase "Sfanta Parascheva" Iaşi (205) Iaşi Romania
15 Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr Victor Babes Timişoara (201) Timişoara Romania
16 Barnsley Hospital NHS Foundation Trust (105) Barnsley United Kingdom
17 Bolton NHS Foundation Trust (122) Bolton United Kingdom
18 Bradford Teaching Hospitals NHS Foundation Trust (103) Bradford United Kingdom BD9 6RJ
19 North Bristol NHS Trust (116) Bristol United Kingdom BS10 5NB
20 County Durham and Darlington NHS Foundation Trust (121) Darlington United Kingdom
21 The Dudley Group NHS Foundation Trust (107) Dudley United Kingdom DY1 2HQ
22 Medway NHS Foundation Trust (108) Gillingham United Kingdom ME7 5NY
23 Hull & East Yorkshire NHS Trust (102) Hull United Kingdom
24 Barts Health NHS Trust (101 and 111) London United Kingdom E1 1FR
25 Royal Free London NHS Foundation Trust (119) London United Kingdom NW3 2QG
26 St George's University Hospitals NHS Foundation Trust (114) London United Kingdom
27 Penine Acute Hospitals NHS Trust (106) Salford United Kingdom M6 8HD
28 Sheffield Hospitals NHS Foundation Trust (104) Sheffield United Kingdom S10 2SB
29 Somerset NHS Foundation Trust (109) Taunton United Kingdom TA1 5DA
30 Walsall Healthcare NHS Trust (113) Walsall United Kingdom WS2 9PS

Sponsors and Collaborators

  • St George Street Capital

Investigators

  • Principal Investigator: Kieran McCafferty, MD, Barts & The London NHS Trust

Study Documents (Full-Text)

More Information

Additional Information:

Publications

None provided.
Responsible Party:
St George Street Capital
ClinicalTrials.gov Identifier:
NCT04516759
Other Study ID Numbers:
  • SGS.1656.201
  • 2020-002211-21
First Posted:
Aug 18, 2020
Last Update Posted:
Apr 25, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Keywords provided by St George Street Capital
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details 170 subjects were screened for participation. 13 subjects were screening failures. 156 subjects were randomized of which 3 subjects withdrew consent prior to start of study medication. 153 subjects started with study treatment.
Pre-assignment Detail
Arm/Group Title AZD1656 (Plus Usual Hospital Care) Matched Placebo (Plus Usual Hospital Care)
Arm/Group Description 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) Matched placebo tablets Placebo: Matched placebo tablets
Period Title: Overall Study
STARTED 80 73
COMPLETED 79 71
NOT COMPLETED 1 2

Baseline Characteristics

Arm/Group Title AZD1656 (Plus Usual Hospital Care) Matched Placebo (Plus Usual Hospital Care) Total
Arm/Group Description 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) Matched placebo tablets Placebo: Matched placebo tablets Total of all reporting groups
Overall Participants 80 73 153
Age (Count of Participants)
<=18 years
0
0%
0
0%
0
0%
Between 18 and 65 years
38
47.5%
31
42.5%
69
45.1%
>=65 years
42
52.5%
42
57.5%
84
54.9%
Sex: Female, Male (Count of Participants)
Female
30
37.5%
26
35.6%
56
36.6%
Male
50
62.5%
47
64.4%
97
63.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
0
0%
0
0%
0
0%
Not Hispanic or Latino
77
96.3%
70
95.9%
147
96.1%
Unknown or Not Reported
3
3.8%
3
4.1%
6
3.9%
Region of Enrollment (Count of Participants)
Romania
19
23.8%
14
19.2%
33
21.6%
Czechia
27
33.8%
22
30.1%
49
32%
United Kingdom
34
42.5%
37
50.7%
71
46.4%
WHO OSCI rating (Count of Participants)
3 - Hospitalised, no oxygen
19
23.8%
13
17.8%
32
20.9%
4 - Hospitalised, oxygen
52
65%
42
57.5%
94
61.4%
5 - Non-invasive ventilation or high flow oxygen
9
11.3%
18
24.7%
27
17.6%
Diabetes Type (Count of Participants)
Type 1
1
1.3%
2
2.7%
3
2%
Type 2
79
98.8%
71
97.3%
150
98%
Vitamin D group (Count of Participants)
< 25 nmol/l
31
38.8%
27
37%
58
37.9%
>= 25 nmol/l
46
57.5%
45
61.6%
91
59.5%
missing
3
3.8%
1
1.4%
4
2.6%

Outcome Measures

1. Primary Outcome
Title Clinical Improvement by Day 14
Description 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.
Time Frame Day 1 to Day 14

Outcome Measure Data

Analysis Population Description
Full Analysis Set: all participants who received at least one dose of treatment
Arm/Group Title AZD1656 (Plus Usual Hospital Care) Matched Placebo (Plus Usual Hospital Care)
Arm/Group Description 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) Matched placebo tablets Placebo: Matched placebo tablets
Measure Participants 80 73
Treatment responder
61
76.3%
51
69.9%
Treatment failure
18
22.5%
21
28.8%
Missing
1
1.3%
1
1.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care)
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.1854
Comments
Method Chi-squared
Comments Chi-squared test on the one-sided significance level of 2.5%
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.9 to 1.32
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
Title Clinical Improvement at Day 7, 14 and 21
Description 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).
Time Frame Day 1 to Day 21

Outcome Measure Data

Analysis Population Description
Full Analysis Set: all participants who received at least one dose of treatment
Arm/Group Title AZD1656 (Plus Usual Hospital Care) Matched Placebo (Plus Usual Hospital Care)
Arm/Group Description 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) Matched placebo tablets Placebo: Matched placebo tablets
Measure Participants 80 73
Score 1: Ambulatory - no limitation of activities
0
0%
0
0%
Score 2: Ambulatory - limitation of activities
0
0%
0
0%
Score 3: Hospitalized, no oxygen therapy
19
23.8%
13
17.8%
Score 4: Hospitalized, oxygen by mask or nasal prongs
52
65%
42
57.5%
Score 5: Hospitalized, non-invasive ventilation or high-flow oxygen
9
11.3%
18
24.7%
Score 6: Hospitalized, intubation or mechanical ventilation
0
0%
0
0%
Score 7: Hospitalized, ventilation + additional organ support - pressors, RTT, ECMO
0
0%
0
0%
Score 8: Death
0
0%
0
0%
Missing
0
0%
0
0%
Score 1: Ambulatory - no limitation of activities
7
8.8%
7
9.6%
Score 2: Ambulatory - limitation of activities
22
27.5%
10
13.7%
Score 3: Hospitalized, no oxygen therapy
15
18.8%
17
23.3%
Score 4: Hospitalized, oxygen by mask or nasal prongs
23
28.8%
26
35.6%
Score 5: Hospitalized, non-invasive ventilation or high-flow oxygen
10
12.5%
5
6.8%
Score 6: Hospitalized, intubation or mechanical ventilation
2
2.5%
3
4.1%
Score 7: Hospitalized, ventilation + additional organ support - pressors, RTT, ECMO
0
0%
0
0%
Score 8: Death
0
0%
5
6.8%
Missing
1
1.3%
0
0%
Score 1: Ambulatory - no limitation of activities
16
20%
14
19.2%
Score 2: Ambulatory - limitation of activities
37
46.3%
30
41.1%
Score 3: Hospitalized, no oxygen therapy
8
10%
7
9.6%
Score 4: Hospitalized, oxygen by mask or nasal prongs
9
11.3%
10
13.7%
Score 5: Hospitalized, non-invasive ventilation or high-flow oxygen
4
5%
2
2.7%
Score 6: Hospitalized, intubation or mechanical ventilation
4
5%
3
4.1%
Score 7: Hospitalized, ventilation + additional organ support - pressors, RTT, ECMO
0
0%
0
0%
Score 8: Death
1
1.3%
6
8.2%
Missing
1
1.3%
1
1.4%
Score 1: Ambulatory - no limitation of activities
20
25%
15
20.5%
Score 2: Ambulatory - limitation of activities
44
55%
41
56.2%
Score 3: Hospitalized, no oxygen therapy
4
5%
0
0%
Score 4: Hospitalized, oxygen by mask or nasal prongs
2
2.5%
5
6.8%
Score 5: Hospitalized, non-invasive ventilation or high-flow oxygen
4
5%
2
2.7%
Score 6: Hospitalized, intubation or mechanical ventilation
4
5%
3
4.1%
Score 7: Hospitalized, ventilation + additional organ support - pressors, RTT, ECMO
0
0%
0
0%
Score 8: Death
1
1.3%
6
8.2%
Missing
1
1.3%
1
1.4%
Score 1: Ambulatory - no limitation of activities
20
25%
15
20.5%
Score 2: Ambulatory - limitation of activities
44
55%
40
54.8%
Score 3: Hospitalized, no oxygen therapy
3
3.8%
0
0%
Score 4: Hospitalized, oxygen by mask or nasal prongs
3
3.8%
5
6.8%
Score 5: Hospitalized, non-invasive ventilation or high-flow oxygen
4
5%
1
1.4%
Score 6: Hospitalized, intubation or mechanical ventilation
4
5%
3
4.1%
Score 7: Hospitalized, ventilation + additional organ support - pressors, RTT, ECMO
0
0%
0
0%
Score 8: Death
1
1.3%
6
8.2%
Missing
1
1.3%
3
4.1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care)
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.0286
Comments Baseline p-value
Method Wilcoxon (Mann-Whitney)
Comments one-side significance level of 2.5%
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care)
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.0786
Comments Day 7 p-value
Method Wilcoxon (Mann-Whitney)
Comments one-side significance level of 2.5%
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care)
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.2169
Comments Day 14 p-value
Method Wilcoxon (Mann-Whitney)
Comments one-side significance level of 2.5%
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care)
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.1860
Comments Day 21 p-value
Method Wilcoxon (Mann-Whitney)
Comments one-sided significance level of 2.5%
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care)
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.2256
Comments Study Drug Discontinuation (SDD) p-value
Method Wilcoxon (Mann-Whitney)
Comments one-sided significance level of 2.5%
3. Secondary Outcome
Title Glycaemic Control
Description 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
Time Frame Day 1 to Day 21

Outcome Measure Data

Analysis Population Description
Full Analysis Set: all participants who at least received one dose of treatment
Arm/Group Title AZD1656 (Plus Usual Hospital Care) Matched Placebo (Plus Usual Hospital Care)
Arm/Group Description 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) Matched placebo tablets Placebo: Matched placebo tablets
Measure Participants 80 73
True
12
15%
13
17.8%
False
68
85%
60
82.2%
True
61
76.3%
58
79.5%
False
19
23.8%
15
20.5%
True
25
31.3%
21
28.8%
False
55
68.8%
52
71.2%
True
74
92.5%
67
91.8%
False
6
7.5%
6
8.2%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care)
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.4006
Comments Increase in Diabetic Medication needed equal or more than 3 days
Method Fisher Exact
Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care)
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.7482
Comments Diabetic Medication is stable/reduced equal or more than 3 days
Method Fisher Exact
Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care)
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.6949
Comments Increase in Diabetic Medication needed at any time during the study
Method Fisher Exact
Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care)
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.5521
Comments Diabetic Medication is stable/reduced at any time during the study
Method Fisher Exact
Comments
4. Secondary Outcome
Title Occurrence of Adverse Events
Description Proportion of Treatment Emergent Adverse Events (TEAEs) leading to study drug discontinuation in patients receiving AZD1656 compared with placebo
Time Frame Day 1 to Day 28

Outcome Measure Data

Analysis Population Description
This analysis includes all participants who received at least one dose of treatment and had at least one post-baseline safety assessment (where the statement that a patient had no AE on the AE eCRF constitutes a safety assessment). 4 patients from the placebo arm are moved to the AZD1656 arm due to having drug in their PK samples. The assignment of patients to the treatment groups are as actually treated.
Arm/Group Title AZD1656 (Plus Usual Hospital Care) Matched Placebo (Plus Usual Hospital Care)
Arm/Group Description 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) Matched placebo tablets Placebo: Matched placebo tablets
Measure Participants 84 69
TEAEs leading to study drug discontinuation
2
2
Other TEAEs
28
21
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care)
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.5875
Comments
Method Fisher Exact
Comments
5. Secondary Outcome
Title Occurrence of Serious Adverse Events
Description Proportion of Serious Adverse Events (SAEs) in patients receiving AZD1656 compared with placebo
Time Frame Day 1 to Day 28

Outcome Measure Data

Analysis Population Description
This analysis includes all patients who received at least one dose of IMP and had at least one post-baseline safety assessment (where the statement that a patient had no AE on the AE eCRF constitutes a safety assessment). 4 patients from the placebo arm are moved to the AZD1656 arm due to having drug in their PK samples. The assignment of patients to the treatment groups are as actually treated.
Arm/Group Title AZD1656 (Plus Usual Hospital Care) Matched Placebo (Plus Usual Hospital Care)
Arm/Group Description 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) Matched placebo tablets Placebo: Matched placebo tablets
Measure Participants 84 69
Serious Adverse Events
4
7
Other AEs
28
17
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care)
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.1129
Comments
Method Fisher Exact
Comments
6. Secondary Outcome
Title Duration of Hospitalisation
Description Time from hospital admission to hospital discharge (in hours) in patients receiving AZD1656 compared with placebo
Time Frame Day 1 to Day 21

Outcome Measure Data

Analysis Population Description
Full Analysis Set: all participant who at least received on dose of treatment
Arm/Group Title AZD1656 (Plus Usual Hospital Care) Matched Placebo (Plus Usual Hospital Care)
Arm/Group Description 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) Matched placebo tablets Placebo: Matched placebo tablets
Measure Participants 80 73
Median (95% Confidence Interval) [hours]
264.3
288.7
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care)
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.1556
Comments
Method Log Rank
Comments
7. Secondary Outcome
Title Mortality Rate
Description Mortality rate in patients receiving AZD1656 compared with placebo.
Time Frame Day 1 to Day 28

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title AZD1656 (Plus Usual Hospital Care) Matched Placebo (Plus Usual Hospital Care)
Arm/Group Description 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) Matched placebo tablets Placebo: Matched placebo tablets
Measure Participants 80 73
Died
4
5%
9
12.3%
Did not die
75
93.8%
63
86.3%
Missing
1
1.3%
1
1.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care)
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.0903
Comments
Method Fisher Exact
Comments The p-value is assessed by means of an Fisher's exact test on the one-sided significance level of 2.5%
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.41
Confidence Interval (2-Sided) 95%
0.13 to 1.26
Parameter Dispersion Type:
Value:
Estimation Comments
8. Secondary Outcome
Title Intubation/Mechanical Ventilation
Description Number of Patients Receiving Intubation/Mechanical Ventilation
Time Frame Day 1 to Day 21

Outcome Measure Data

Analysis Population Description
Full Analysis Set: all participants who at least received one dose of treatment
Arm/Group Title AZD1656 (Plus Usual Hospital Care) Matched Placebo (Plus Usual Hospital Care)
Arm/Group Description 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) Matched placebo tablets Placebo: Matched placebo tablets
Measure Participants 80 73
Receiving Intubation/Mechanical Ventilation
3
3.8%
3
4.1%
Not Receiving Intubation/Mechanical Ventilation
76
95%
69
94.5%
Missing
1
1.3%
1
1.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care)
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.6144
Comments
Method Fisher Exact
Comments One-sided significance level of 2.5%
9. Post-Hoc Outcome
Title Mortality Rate
Description Mortality rate from randomization up to and including 168 hours post randomization
Time Frame Randomization to 168 hours post randomization

Outcome Measure Data

Analysis Population Description
Full Analysis Set: all participant who received at least one dose of treatment; patients who withdrew consent are categorised as missing
Arm/Group Title AZD1656 (Plus Usual Hospital Care) Matched Placebo (Plus Usual Hospital Care)
Arm/Group Description 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) Matched placebo tablets Placebo: Matched placebo tablets
Measure Participants 80 73
Died
0
0%
6
8.2%
Did not die
79
98.8%
66
90.4%
Missing
1
1.3%
1
1.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care)
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.0105
Comments
Method Fisher Exact
Comments one-sided significance level of 2.5%
10. Post-Hoc Outcome
Title Proportion of Patients Discharged up to and Including 168 Hours Having a WHO OSCI Rating of 1 or 2
Description Proportion of Patients Being Discharged From Hospital up to and Including 168 hrs Having WHO OSCI Rating of 1 or 2
Time Frame Day 1 up to and including 168 hours post randomization

Outcome Measure Data

Analysis Population Description
Full Analysis Set: all participants who had at least one dose of treatment
Arm/Group Title AZD1656 (Plus Usual Hospital Care) Matched Placebo (Plus Usual Hospital Care)
Arm/Group Description 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) Matched placebo tablets Placebo: Matched placebo tablets
Measure Participants 80 73
Discharged from hospital (within 168 hrs with WHO 1 or 2)
30
37.5%
18
24.7%
Not discharged from Hospital (within 168 hrs with WHO 1 or 2)
49
61.3%
54
74%
Missing
1
1.3%
1
1.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AZD1656 (Plus Usual Hospital Care), Matched Placebo (Plus Usual Hospital Care)
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.062
Comments
Method Fisher Exact
Comments one-sided significance level of 2.5%

Adverse Events

Time Frame All AEs, including SAEs, were captured after signing the informed consent and until 7 days after treatment discontinuation (up to a maximum of 28 days).
Adverse Event Reporting Description Serious and other Adverse Events were assessed using the Safety Set (SAF) dataset. The SAF dataset included 84 patients in the AZD1656 arm and 69 patients in the placebo arm, All-Cause Mortality was assessed using the Full Analysis Set (FAS) dataset. The FAS dataset included 80 patients in the AZD1656 arm and 73 patients in the placebo arm.
Arm/Group Title AZD1656 (Plus Usual Hospital Care) Matched Placebo (Plus Usual Hospital Care)
Arm/Group Description 50mg film-coated tablets at a dose of 100mg BID AZD1656: 50mg film-coated tablets (at daily dose of 100mg BID) Matched placebo tablets Placebo: Matched placebo tablets
All Cause Mortality
AZD1656 (Plus Usual Hospital Care) Matched Placebo (Plus Usual Hospital Care)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 4/80 (5%) 9/73 (12.3%)
Serious Adverse Events
AZD1656 (Plus Usual Hospital Care) Matched Placebo (Plus Usual Hospital Care)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 10/84 (11.9%) 19/69 (27.5%)
Cardiac disorders
Angina unstable 1/84 (1.2%) 1 0/69 (0%) 0
Cardio-respiratory arrest 0/84 (0%) 0 1/69 (1.4%) 1
Cardiogenic shock 0/84 (0%) 0 1/69 (1.4%) 1
Myocardial infarction 0/84 (0%) 0 1/69 (1.4%) 1
Ventricular tachycardia 0/84 (0%) 0 1/69 (1.4%) 1
Gastrointestinal disorders
Pancreatitis acute 0/84 (0%) 0 1/69 (1.4%) 1
Hepatobiliary disorders
Acute hepatic failure 1/84 (1.2%) 1 0/69 (0%) 0
Infections and infestations
Abcess limb 0/84 (0%) 0 1/69 (1.4%) 1
Gastroenteritis 0/84 (0%) 0 1/69 (1.4%) 1
Pneumonia bacterial 0/84 (0%) 0 1/69 (1.4%) 1
Septic shock 0/84 (0%) 0 1/69 (1.4%) 1
COVID-19 2/84 (2.4%) 2 5/69 (7.2%) 5
COVID-19 pneumonia 2/84 (2.4%) 2 2/69 (2.9%) 2
Sepsis 0/84 (0%) 0 1/69 (1.4%) 1
Injury, poisoning and procedural complications
Fall 0/84 (0%) 0 2/69 (2.9%) 2
Metabolism and nutrition disorders
Dehydration 1/84 (1.2%) 1 0/69 (0%) 0
Hypophagia 1/84 (1.2%) 1 0/69 (0%) 0
Psychiatric disorders
Suicide attempt 1/84 (1.2%) 1 0/69 (0%) 0
Vascular disorders
Circulatory collapse 1/84 (1.2%) 1 0/69 (0%) 0
Other (Not Including Serious) Adverse Events
AZD1656 (Plus Usual Hospital Care) Matched Placebo (Plus Usual Hospital Care)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 43/84 (51.2%) 17/69 (24.6%)
Blood and lymphatic system disorders
Anaemia 0/84 (0%) 0 2/69 (2.9%) 2
Leucocytosis 1/84 (1.2%) 1 0/69 (0%) 0
Neutrophilia 1/84 (1.2%) 1 0/69 (0%) 0
Thrombocytopenia 0/84 (0%) 0 1/69 (1.4%) 1
Cardiac disorders
Atrial fibrillation 2/84 (2.4%) 2 0/69 (0%) 0
Atrial flutter 0/84 (0%) 0 1/69 (1.4%) 1
Ear and labyrinth disorders
Ear pain 1/84 (1.2%) 1 0/69 (0%) 0
Gastrointestinal disorders
Diarrhoea 2/84 (2.4%) 2 0/69 (0%) 0
Abdominal tenderness 1/84 (1.2%) 1 0/69 (0%) 0
Constipation 0/84 (0%) 0 1/69 (1.4%) 1
Hepatobiliary disorders
Hepatitis toxic 1/84 (1.2%) 1 0/69 (0%) 0
Infections and infestations
Oral candidiasis 1/84 (1.2%) 1 1/69 (1.4%) 1
Sepsis 1/84 (1.2%) 1 0/69 (0%) 0
Cystitis 0/84 (0%) 0 1/69 (1.4%) 1
Device related infection 1/84 (1.2%) 1 0/69 (0%) 0
Oral fungal infection 1/84 (1.2%) 1 0/69 (0%) 0
Upper respiratory tract infection 0/84 (0%) 0 1/69 (1.4%) 1
Urinary tract infection 1/84 (1.2%) 1 0/69 (0%) 0
Vulvovaginal mycotic infection 0/84 (0%) 0 1/69 (1.4%) 1
Investigations
Aspartate aminotransferase increased 1/84 (1.2%) 1 0/69 (0%) 0
Blood glucose decreased 1/84 (1.2%) 1 0/69 (0%) 0
Gamma-glutamyltransferase increased 1/84 (1.2%) 1 0/69 (0%) 0
Vitamin D decreased 1/84 (1.2%) 1 0/69 (0%) 0
Metabolism and nutrition disorders
Hypoglycaemia 8/84 (9.5%) 13 1/69 (1.4%) 1
Hyperglycaemia 4/84 (4.8%) 4 1/69 (1.4%) 1
Hypokalaemia 4/84 (4.8%) 4 0/69 (0%) 0
Hyperkalaemia 2/84 (2.4%) 2 0/69 (0%) 0
Nervous system disorders
Reversible ischaemic neurological deficit 1/84 (1.2%) 1 0/69 (0%) 0
Psychiatric disorders
Restlessness 0/84 (0%) 0 1/69 (1.4%) 1
Renal and urinary disorders
Acute kidney injury 1/84 (1.2%) 1 0/69 (0%) 0
Dysuria 0/84 (0%) 0 1/69 (1.4%) 1
Urinary retention 1/84 (1.2%) 1 0/69 (0%) 0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism 4/84 (4.8%) 4 3/69 (4.3%) 3
Hiccups 0/84 (0%) 0 1/69 (1.4%) 1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Mike Johnson, Managing Director
Organization St George Street Capital
Phone +447768335460
Email mike@sgscapital.org
Responsible Party:
St George Street Capital
ClinicalTrials.gov Identifier:
NCT04516759
Other Study ID Numbers:
  • SGS.1656.201
  • 2020-002211-21
First Posted:
Aug 18, 2020
Last Update Posted:
Apr 25, 2022
Last Verified:
Apr 1, 2022