STOP-COVID19: Superiority Trial Of Protease inhibition in COVID-19 (coronavirus infection)
- Conditions
- COVID-19 (SARS-CoV-2 infection)Infections and Infestations
- Registration Number
- ISRCTN30564012
- Lead Sponsor
- niversity of Dundee
- Brief Summary
2022 Results article in https://pubmed.ncbi.nlm.nih.gov/36075243/ (added 09/09/2022)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 406
Current inclusion criteria as of 10/11/2020:
1. Aged =16 years
2. SARS-CoV-2 infection (clinically suspected+ or laboratory confirmed*).
3. Admitted to hospital as in-patient less than 96 hours prior to randomisation^
4. Illness of any duration, and at least one of the following:
4.1. Radiographic infiltrates by imaging (e.g. chest x-ray, computed tomography (CT) scan) OR
4.2. Evidence of rales/crackles on physical examination OR
4.3. Peripheral capillary oxygen saturation (SpO2) =94% on room air prior to randomization OR
4.4. Requiring supplemental oxygen OR
4.5. Lymphocyte count <1 x 10(9) cells/l
5. Participant (or legally authorized representative) provides written informed consent
6. Able to take oral medication
7. Participant (or legally authorised representative) understands and agrees to comply with planned trial procedures
*Laboratory-confirmed: SARS-CoV-2 infection as determined by polymerase chain reaction (PCR), or other commercial or public health assay in any specimen < 96 hours prior to randomization.
+Clinically suspected: in general, SARS-CoV-2 infection should be suspected when a patient presents with (i) typical symptoms (e.g. influenza-like illness with fever and muscle pain, or respiratory illness with cough and shortness of breath); and (ii) compatible chest X-ray findings (consolidation or ground-glass shadowing); and (iii) alternative causes have been considered
unlikely or excluded (e.g. heart failure, influenza). However, the diagnosis remains a clinical one based on the opinion of the managing doctor.
^Where a patient has been admitted to hospital for a non COVID-19 reason and develops COVID19 symptoms whilst an in-patient, randomisation may occur up to 96 hours from onset of symptoms.
_____
Previous inclusion criteria:
1. Aged =16 years
2. Laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR), or other commercial or public health assay in any specimen < 96 h prior to randomization
3. Admitted to hospital as in-patient
4. Illness of any duration, and at least one of the following:
4.1. Radiographic infiltrates by imaging (e.g. chest x-ray, computed tomography (CT) scan) OR
4.2. Evidence of rales/crackles on physical examination OR
4.3. Peripheral capillary oxygen saturation (SpO2) =94% on room air prior to randomization OR
4.4. Requiring supplemental oxygen OR
4.5. Lymphocyte count <1 x 10(9) cells/l
5. Participant (or legally authorized representative) provides written informed consent
6. Able to take oral medication
7. Participant (or legally authorised representative) understands and agrees to comply with planned trial procedures
Current exclusion criteria as of 21/01/2021:
1. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 5 times the upper limit of normal, result within 72 hours of randomization (the result closest to randomization should be used if several results are available).
2. History of severe liver disease
3. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR < 30), result within 72 hours of randomization (the result closest to randomization should be used if several results are available)
4. Absolute neutrophil count less than 1.0 x 109 cells per L within 72 hours of randomization (the result closest to randomization should be used if several results are available)
5. Current treatments with potent Cyp3A4 inducers/inhibitors (e.g Itraconazole, Ketoconazole, diltiazem, verapamil, phenytoin or rifampicin)
6. HIV treatments - current treatment with protease/integrase inhibitors or non-nucleoside reverse transcriptase inhibitors*
7. Pregnant or breast feeding
8. Anticipated transfer to another hospital which is not a trial site within 24 hours
9. Allergy to Brensocatib
10. Use of any investigational drug within five times of the elimination half-life after the last trial dose or within 30 days, whichever is longer. Co-enrolment with COVID-19 trials is allowed as per co-enrolment agreements and/or individual decision by the CI
11. Women of child-bearing potential must be willing to have pregnancy testing prior to trial entry.
*The Liverpool HIV checker (https://www.hiv-druginteractions.org/checker) should be used to check for any HIV drug interactions. Simvastatin could be used as a surrogate for Brensocatib as it metabolised similarly by CYP 3A4 pathway
_____
Previous exclusion criteria as of 10/11/2020:
1. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >5x the upper limit of normal, result within 72 h of randomization (the result closest to randomization should be used if several results are available)
2. History of severe liver disease
3. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR <30), result within 72 h of randomization (the result closest to randomization should be used if several results are available)
4. Absolute neutrophil count less than 1.0 x 10(9) cells/l within 72 h of randomization (the result closest to randomization should be used if several results are available)
5. Current treatment with Itraconazole, Ketoconazole, diltiazem, verapamil, phenytoin or rifampicin
6. HIV treatments - current treatment with protease/integrase inhibitors or non-nucleoside reverse transcriptase inhibitors*
7. Pregnant or breast feeding
8. Anticipated transfer to another hospital which is not a trial site within 24 hours
9. Allergy to brensocatib
10. Use of any investigational drug within 5 times the elimination half-life after the last trial dose or within 30 days, whichever is longer
*The Liverpool HIV checker (https://www.hiv-druginteractions.org/checker) should be used to check for any HIV drug interactions. Simvastatin could be used as a surrogate f
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Participant clinical status (on a 7-point ordinal scale); up to day 29
- Secondary Outcome Measures
Name Time Method