University of Oxford to test effectiveness of respiratory drug in improving COVID-19 outcomes, with potential to reduce the need for specialist ventilation

Research title

To determine whether administration of almitrine bismesylate can ameliorate hypoxaemia in COVID-19 and augment effectiveness of supplementary oxygen therapy and respiratory support

Summary

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 developed in France initially 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 redistributing blood flow in the lungs. Based on these findings, the drug will be tested in humans with COVID-19 to test its effectiveness.

Research organisation

University of Oxford

Researchers

Principal Investigator:

Co-investigators:

  • 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 and death. 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.

For many patients, this problem can be managed with supplementary oxygen together with standard methods of respiratory support. For other patients, this is not enough. While further treatment options exist, they can only be delivered in a few, highly specialist, centres, and these may not have the capacity to treat the number of patients who could potentially benefit.

Further treatment options are therefore 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. Instead, it diverts that blood to healthier regions of 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 a suitable treatment regime.

Researchers secured funding from LifeArc to conduct a randomised controlled trial to assess whether almitrine bismesylate can relieve hypoxemia in COVID-19 infections versus placebo. The study population will be limited to patients with a clinically confident or proven diagnosis of COVID-19 and who are hypoxaemic in the presence of moderate intervention to maintain oxygenation. They will already be receiving supplementary oxygen therapy, and may already be receiving either non-invasive respiratory support or be intubated and undergoing mechanical ventilation.

The trial is split into two phases. The first is to test whether almitrine has an effect on oxygenation and involves a single test dose of almitrine. The second phase, which depends on whether almitrine affects oxygenation, is to administer almitrine over a seven-day period and determine whether it is effective in reducing the need for other forms of ventilatory support, such as intubation and mechanical ventilation or extracorporeal membrane oxygenation. Patients for the first phase of the trial will follow a randomisation ratio of 2:1, with two patients in the treatment arm to receive a single dose of almitrine, for each one patient in the control arm, to receive a single dose of placebo. Patients in the second phase of the trial will follow a randomisation ratio of 1:1 and will receive regular treatment with either almitrine or placebo over the seven-day period.

The trial will be conducted at the Adult Intensive Care Unit and Respiratory and medical wards of Oxford University Hospitals’ John Radcliffe Hospital, along with the Adult Intensive Care Units at the Royal Berkshire NHS Foundation Trust and University Hospital of Wales, Cardiff. The almitrine will take three months to manufacture. Once the almitrine becomes available, it is anticipated that the first phase of the study will take one month to complete, and the second phase will take four months to complete. The results should become available one month after completion of the last patient.