COVID-19 (SARS-CoV-2 infection) Infections and Infestations
Conditions
Interventions
Design
Participants will receive an oral/via NG tube course for 7 days of the drug (56 patients) or control (56 patients) and will be studied over a 7-day period to see whether the typ
Prost et al, 1991
Esnault et al, 2019) used an intravenous infusion of either 0.25 mg/kg or 0.5 mg
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Hospitalised patients 2. Male or female, aged 18 and above 3. Clinically confident or proven COVID-19 disease* who require respiratory support** and who have not undergone significant de-escalation of respiratory support*** (i.e. are not in a recovery phase) 4. Female participants of childbearing potential must be willing to use effective contraception for two weeks after the final dose of IMP. Women will be advised to use a hormonal method, an intrauterine device (IUD) or intrauterine system (IUS), a barrier method or abstinence. *A clinically confident diagnosis is made where there is either swab positivity for COVID-19, or where the clinical presentation (including any of symptoms, clinical chemistry (e.g. raised D-dimer, raised CRP) and radiology (CXR, CT or ultrasound findings)) is consistent with likely COVID-19 infection. A pre-planned subgroup analysis will compare the primary outcome for those with swab positive and “clinically likely” disease. **At the time of recruitment, patients will be at least moderate oxygen therapy (> 4 l/min O2 flow to mask or nasal cannulae; FiO2 > 0.3 for Venturi mask) to maintain pulse oximeter saturation, SpO2, in the target range set by the treating clinician. Other higher levels of oxygen support (including higher doses of oxygen, non-invasive respiratory support (continuous positive airway pressure (CPAP), high-flow nasal oxygen, or bi-level non-invasive positive pressure ventilation (NIPPV)) and invasive mechanical ventilation via an endotracheal tube can all be included, but patients are excluded if they have received > 72 hours of invasive mechanical ventilation during their current illness. ***De-escalation of respiratory support is defined as a significant reduction in respiratory support that maintains saturation within the treating physicians’ target range within 24 hours of inclusion to this study. A significant reduction is any change in the mode of oxygen delivery (i.e. intubated to non-invasive ventilation, non-invasive ventilation to standard oxygen therapy, or reduction of standard “wall” oxygen of more than 3 litres/min). Changes less than this will not be considered to be significant. Additional inclusion criteria for the physiological sub-study: 1. Arterial line in place for clinical care 2. Receiving either non-invasive respiratory support or invasive mechanical ventilation for which the inspired oxygen fraction can be measured
Exclusion criteria
Exclusion criteria: 1. Female participant who is pregnant, lactating or planning pregnancy during the course of the trial (women of childbearing potential as determined by the clinician must have a negative urine pregnancy test) 2. Pre-existing significant liver disease or a baseline AST or ALT which is >3x the upper limit of normal 3. A previously established diagnosis of significant pulmonary hypertension defined as a resting pulmonary artery pressure of >50 mmHg on right heart catheter or echocardiography 4. Received invasive mechanical ventilation for > 72 h during current illness, at the time of recruitment into the study 5. In the clinicians’ view, expected to survive 2mM)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Level of respiratory support measured using an ordinal scale at baseline and days 1-7 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Time to de-escalation of respiratory support, measured at baseline and days 1-7 2. Daily circulating almitrine levels measured by taking daily blood samples for storage at baseline and days 1-7 3. Mortality captured via medical records/phone follow up at 30 days | — |
Countries
United Kingdom
Outcome results
None listed