A therapeutic study in pre-ICU patients admitted with coronavirus using repurposed drugs

Phase 4

Completed

• Conditions: ate stage 1/stage 2 COVID-19-related disease, COVID-19 (SARS-CoV-2 infection); Infections and Infestations; COVID-19 (SARS-CoV-2 infection)

• Registration Number: ISRCTN11188345
• Lead Sponsor: Cambridge University Hospitals NHS Foundation Trust

Brief Summary

2020 Protocol article in https://pubmed.ncbi.nlm.nih.gov/32641154/ protocol (added 10/07/2020) 2023 Results article in https://pubmed.ncbi.nlm.nih.gov/37977159/ (added 05/03/2024)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-05-15
• Study Completion: 2021-10-01
• Last Update Posted: 18 March 2024

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 417

Inclusion Criteria

1. Be aged 18 years and over
2. Have clinical picture strongly suggestive of COVID-19-related disease (with/without positive COVID-19 test) AND
2.1. Risk count (as defined above) >3 OR
2.3. Risk count 3 if risk count includes Radiographic severity score >3”
3. Be considered an appropriate subject for intervention with immunomodulatory in the opinion of the investigator
4. Be able to be maintained on venous thromboembolism prophylaxis or current maintenance therapy during inpatient dosing period, according to local guidelines

Exclusion Criteria

1. Inability to supply direct informed consent from patient or from Next of Kin or Independent Healthcare Provider on behalf of patient
2. Mechanical ventilation at time of prior to dosing
3. Contraindications to study drugs, including hypersensitivity to the active substances or any of the excipients
4. Currently on any of the study investigational medicinal products
5. Known unresolved Neisseria meningitidis infection
6. Unwilling to be vaccinated against Neisseria meningitidis or receive prophylactic antibiotic cover until 2 weeks after vaccination
7. Known active tuberculosis (no blood screening required)
8. Known active Hepatitis B or C (no blood screening required); active varicella zoster.
9. Concurrent participation in any interventional clinical trial including COVID-19-related disease trials (observational studies allowed)
10. Patient moribund at presentation or screening
11. Pregnancy at screening (or unwillingness to adhere to pregnancy advice in protocol)
12. Unwillingness to adhere to breastfeeding advice in protocol.
13. Either alanine transaminase or aspartate transaminase (ALT or AST) > 5 times the upper limit of normal
14. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. Cockcroft Gault estimated creatinine clearance < 30 ml /min/1.73 m2)
15. Currently receiving probenecid or chronic IVIG treatment
16. 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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Time to incidence (up to Day 14) of the composite endpoint of:<br>1. Death<br>2. Mechanical ventilation<br>3. Extracorporeal membrane oxygenation <br>4. Cardiovascular organ support (balloon pump or inotropes)<br>5. Renal failure (estimated creatinine clearance (by Cockcroft-Gault formula) <15 ml /min/1.73 m2), haemofiltration or dialysis<br>All measured using patient records

Secondary Outcome Measures

Name	Time	Method
Measured using patient records:<br>1. Change in clinical status as assessed on 7-point ordinal scale compared to baseline<br>2. Time to each of the individual endpoints of the composite primary outcome measure<br>3. Proportion of patients with adverse events of special interest in each treatment arm<br>4. Time to Sp02 >94% on room air (excluding chronically hypoxic individuals)<br>5. Time to first negative SARS-CoV2 PCR<br>6. Duration of oxygen therapy (days)<br>7. Duration of hospitalisation (days)<br>8. All cause mortality at day 28<br>9. Time to clinical improvement (defined as >2 point improvement from day 1 on 7-point ordinal scale)<br><br>Pulmonary 7-point scale:<br>1 Death<br>2 Mechanical Ventilation or ECMO<br>3 Non-invasive ventilation or high flow oxygen<br>4 Low flow oxygen<br>5 Hospitalised – no oxygen<br>6 Discharged; normal activities not resumed<br>7 Discharged; normal activities resumed