COVID-19 trials registries data warehouse

https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-002567-57/GB

University of Oxford / Clinical Trials and Research Governance - CTRG

ctrg@admin.ox.ac.uk

2020-10-22

Recruiting

RCT

Randomized

Parallel

Blind label

multi-center

Treatment

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.

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

2

University of Oxford / Clinical Trials and Research Governance

18

100

United Kingdom

Moderate/severe/critical disease at enrollment

5: Moderate/severe/critical disease at enrollment

112

Change in level of respiratory support over 7 days of treatment

Declared number of arm (3.0) differs from found arms (2.0)

Phase 4

[{"arm_notes": "", "treatment_id": 2187, "treatment_name": "Placebo", "treatment_type": "Placebo", "pharmacological_treatment": "Placebo"}, {"arm_notes": "", "treatment_id": 68, "treatment_name": "Almitrine", "treatment_type": "Respiratory agents", "pharmacological_treatment": "Pharmacological treatment"}]