Covid-19 MedDRA version: 21.1 Level: PT Classification code 10001053 Term: Acute respiratory failure System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: Almitrine Bimesylate
Pharmaceutical Form: Capsule
INN or Proposed INN: Almitrine Bismesylate
CAS Number: 29608-49-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentr
Sponsors
University of Oxford / Clinical Trials and Research Governance
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Hospitalised patients • Male or female, aged 18 and above • 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). • Female participants of childbearing potential must be willing to use effective contraception for two weeks after 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 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 • Arterial line in place for clinical care • Receiving either non-invasive respiratory support or invasive mechanical ventilation for which the inspired oxygen fraction can be measured. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 92 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: • 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) • Pre-existing significant liver disease or a baseline AST or ALT which is >3x the upper limit of normal. • A previously established diagnosis of significant pulmonary hypertension defined as a resting pulmonary artery pressure of >50 mmHg on right heart catheter or echocardiography. • Received invasive mechanical ventilation for >72h during current illness, at the time of recruitment into the study • In the clinicians’ view, expected to survive <24 hours • Patients who, in the absence of Covid-19, would be unable to give informed consent. • Hypersensitivity to almitrine
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether administration of almitrine bismesylate can ameliorate hypoxaemia in Covid-19 and augment the effectiveness of supplemental oxygen therapy and respiratory support. ;Secondary Objective: To measure the time to de-escalation of respiratory support (if it occurs) To assess the impact of the oral almitrine on daily circulating almitrine levels. To assess the impact of almitrine on mortality from COVID-19 Physiological sub-study: To understand the relationship between oral almitrine administration and arterial oxygenation To understand the relationship between oral almitrine administration and plasma almitrine levels. ;Primary end point(s): Change in level of respiratory support over 7 days of treatment ;Timepoint(s) of evaluation of this end point: Daily level of respiratory support for 7 days during almitrine/placebo administration | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Time to de-escalation of respiratory support (if it occurs). Daily blood almitrine concentrations. Mortality at 30 days captured via medical records / phone follow up. Sub-Study Time profile for change in PaO2/FiO2 and blood almitrine concentration hourly over 4 hours post almitrine/placebo. Time profile of blood almitrine concentration hourly over 4 hours post almitrine/placebo ;Timepoint(s) of evaluation of this end point: During 7 days after administration of almitrine/placebo. During 7 days after administration of almitrine/placebo. Mortality at 30 day Sub-study During 4 hours after administration of almitrine/placebo. During 4 hours after administration of almitrine/placebo | — |
Countries
United Kingdom
Contacts
Public ContactCTRG
University of Oxford / Clinical Trials and Research Governance
Outcome results
None listed