mulTi-Arm Therapeutic Study in Pre-ICu Patients Admitted With Covid-19 - Experimental Drugs and Mechanisms
COVID-19
About this trial
This is an interventional treatment trial for COVID-19
Eligibility Criteria
General Inclusion Criteria:
- Be aged 18 and over
Have clinical picture strongly suggestive of COVID-19-related disease (with/without positive COVID-19 test) AND
- Risk count (as defined below) >3 OR
- Risk count ≥3 if it includes "Radiographic severity score >3"
- Be hospitalized or eligible for hospitalization on clinical grounds
- Be considered an appropriate subject for intervention with immunomodulatory or other disease modifying agents in the opinion of the investigator
General Exclusion Criteria:
- Inability to supply direct informed consent from patient or from Next of Kin or Independent Healthcare Provider on behalf of patient
- Invasive mechanical ventilation at time of screening
- Contraindications to study drugs, including hypersensitivity to the active substances or any of the excipients
- Currently on any of the study investigational medicinal products
- Concurrent participation in an interventional clinical trial (observational studies allowed)
- Patient moribund at presentation or screening
- Pregnancy at screening
- Unwilling to stop breastfeeding during treatment period
- Known severe hepatic impairment (with or without cirrhosis)
- Requiring dialysis Cockcroft Gault estimated creatinine clearance < 30 ml /min/1.73m2 at screening
- Inability to swallow at screening visit
- Any medical history or clinically relevant abnormality that is deemed by the principal investigator and/or medical monitor to make the patient ineligible for inclusion because of a safety concern.
EDP1815-Specific Exclusion Criteria:
- Patient is taking a systemic immunosuppressive agent such as, but not limited to, oral steroids, methotrexate, azathioprine, ciclosporin or tacrolimus, unless these are given as part of COVID standard of care treatment.
- Patient has known primary or secondary B cell disorder
Dapagliflozin- and Ambrisentan-Specific Exclusion Criteria:
- Type 1 diabetes
- Known idiopathic pulmonary fibrosis
- Previous hospital admission with ketoacidosis
- Patients concurrently on other SGLT2 inhibitors
- History of symptomatic heart failure within 3 months of admission
- Sustained blood pressure below 100/70 mmHg at admission
- Metabolic acidosis defined as pH< 7.25 AND ketones > 3.0 mmol/L
- Alanine transaminase and/or aspartate transaminase (ALT and/or AST) > 3 times the upper limit of normal (only one needs to be measured)
Risk Count
Patients will be given a Risk Count equal to the cumulative points received for the following criteria (no = 0 points, yes = 1 point):
Male gender, Age > 40 years, Non-white ethnicity, Diabetes, Hypertension, Neutrophils > 8.0x10^9/L, CRP > 40mg/L, Radiographic severity score >3
Sites / Locations
- Cambridge University Hospitals NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Active Comparator
Experimental
Experimental
Standard of care
EDP1815
Dapagliflozin and Ambrisentan
Standard of care
1.6 x 10^11 cells dosage-in-capsule orally twice per day for up to 7 days (with the option to extend up to 14 days), on top of standard of care
Ambrisentan 5mg tablet orally once per day for up to a maximum of 14 days and Dapagliflozin 10mg tablet orally once per day for up to a maximum of 14 days, on top of standard of care