Testing the effectiveness of almitrine bismesylate in the treatment of COVID-19

Not Applicable

• Conditions: COVID-19 (SARS-CoV-2 infection); Infections and Infestations

• Registration Number: ISRCTN11713182
• Lead Sponsor: niversity of Oxford

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-12-02
• Last Update Posted: 5 January 2021
• Study Completion: 2021-09-30

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 116

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

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 < 24 hours
6. Patients who, in the absence of COVID-19, would be unable to give informed consent
7. Hypersensitivity to almitrine
8. A previously established diagnosis of right ventricular dysfunction that is clinically significant in the opinion of the treating physician
9. Hyperlactataemia (lactate >2mM)

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
evel of respiratory support measured using an ordinal scale at baseline and days 1-7

Secondary Outcome Measures

Name	Time	Method
<br> 1. Time to de-escalation of respiratory support, measured at baseline and days 1-7<br> 2. Daily circulating almitrine levels measured by taking daily blood samples for storage at baseline and days 1-7<br> 3. Mortality captured via medical records/phone follow up at 30 days<br>