University of Oxford to test effectiveness of respiratory drug in improving COVID-19 outcomes, with potential to reduce the need for specialist ventilation
To determine whether administration of almitrine bismesylate can ameliorate hypoxaemia in COVID-19 and augment effectiveness of supplementary oxygen therapy and respiratory support.
The University of Oxford, in collaboration with clinicians in Wales and Berkshire and with funding from LifeArc, is set to commence clinical trials testing almitrine in COVID-19 patients at three UK hospitals. Almitrine is a drug that was developed in France to treat lung diseases like chronic obstructive pulmonary disease (COPD). Small scale trials have previously shown that it can improve oxygen saturation in patients with acute respiratory distress syndrome (ARDS) by redirecting blood flow within the lungs. Based on these findings, the drug will be tested in humans with COVID-19 to test its effectiveness.
- Dr Nick Talbot
- Peter Robbins, University of Oxford
- Matthew Frise, Royal Berkshire NHS Foundation Trust,
- Matthew Wise, University Hospital of Wales,
- Christopher Schofield, University of Oxford,
- Keith Dorrington, University of Oxford
- Najib Rahman, University of Oxford
Potential of repurposed therapeutic for COVID-19 pandemic
One of the main features of severe COVID-19 infections is the reduction in the level of oxygen circulating in the blood. This is known as hypoxemia and can lead to organ failure. Normally, oxygen is gathered as blood passes through the lungs. However, in cases of COVID-19 infection, patients can suffer from ‘shunt flow’, which means circulating blood passes through the lungs without receiving oxygen from the alveoli. While this issue can be managed with specialist equipment, these facilities can only be accessed in selected centres without the capacity to treat the number of patients who could potentially benefit; further treatment options are needed.
The drug almitrine is a respiratory stimulant which, when used to treat patients with acute respiratory distress syndrome (ARDS), has been shown to reduce shunt flow by redirecting blood flow within the lungs, allowing more oxygen to pass into the blood. By testing this drug in COVID-19 patients it is hoped that similar findings will be observed and insights can be gained into the optimal design of an oral treatment regimen.
Researchers secured funding from LifeArc to conduct a randomised controlled trial to assess whether orally administered almitrine bismesylate can relieve hypoxemia in COVID-19 infections versus oral placebo. The study population will be limited to willing hospitalised patients who have tested positive for COVID-19 and are requiring significant clinical intervention, in the form of supplementary oxygen with or without ventilatory support, to relieve their hypoxaemia. The trial will follow a randomisation ratio of 1:1, with each patient in the treatment arm receiving oral almitrine bismesylate, matched by a patient in the control arm receiving oral placebo. Participants will receive oral almitrine bismesylate or placebo every 4 hours for 7 days.
In the trial, the change in level of respiratory support over 7 days of treatment will be measured to know if almitrine bimesylate is effective. The level of respiratory support is gauged by the amount of oxygen required and the level of ventilatory support required according to an accepted ordinal scale.
The trial will be conducted at the Royal Berkshire NHS Foundation Trust (Reading), at the University Hospital of Wales (Cardiff) and at the John Radcliffe Hospital (Oxford).