COVID-19 Clinical Trials and Expanded Access

Some patients infected with COVID-19 require hospitalisation and develop patients a severe form of a lung disease called respiratory distress syndrome (ARDS). In these patients, the lungs become severely inflamed because of the virus. The inflammation causes fluid from nearby blood vessels to leak into the tiny air sacs in the lungs, making breathing increasingly difficult. This fluid forms small clots in the air sacs, creating a barrier until the cells regenerate. In some patients, this clot does not disappear in a timely fashion or interferes with the development of the new cells. Furthermore, the small clots in the air sacs obstruct the air and oxygen getting deep into the lungs, interfering with proper ventilation. The trial will recruit patients with COVID-19 induced ARDS. Eligible patients (or if patients lack capacity, their legal representative) will be provided with an information sheet and informed consent will be sought. Eligibility will be mainly assessed via routine clinical assessments. Patients will receive a nebulised version of a type of drug called tissue plasminogen activator (rt-PA) that is inhaled using a nebuliser. This is normally a drug used to break down blood clots. In this situation though, it might be useful for stopping clots forming in the lungs, because these might lead to even more difficulties with breathing. The study will run two cohorts sequentially. In cohort 1, 9 consented patients received nebulised rtPA in addition to SOC. 6 patients were receiving IMV and 3 were receiving non invasive support with NIV or CPAP or high flow oxygen or standard oxygen therapy. As an observational arm, matched historical controls who received standard of care were also recruited at a ratio of 2 controls to every 1 treatment arm patient, resulting in 18 historical controls. Originally, the study aimed to recruit 12 patients with 6 on each ventilation type (IMV and non-invasive oxygen support). This would have resulted in 24 historical controls. After the first wave of COVID-19 cases decreased in August 2020 in the UK it became difficult to continue recruitment, so recruitment closed for cohort 1. With a second surge underway in early 2021, cohort 2 will aim to recruit more patients during this period to provide more data on the safety of rtPA. Fewer timepoints will be collected, which will allow for more rapid recruitment while at the same time not compromising safety monitoring. A more flexible dosing regimen for rtPA will be utilised. 30 patients will be recruited in total, with an aim to recruit a minimum of 10 IMV patients and 10 patients on non-invasive oxygen support. To evaluate efficacy, the improvement of oxygen levels over time and safety will be be monitored throughout. Blood samples will be taken to measure markers of clotting and inflammation in both groups. From the end of the treatment phase both groups will be followed up in accordance with SOC for 28 days from the day of first dose of rtPA.

This is an open-label, controlled, single-centre pilot study of nivolumab in adult patients with COVID-19. This clinical study aims to evaluate efficacy of anti-PD1 antibody in relation to viral clearance and its safety.

This is a randomized, open-label phase II study designed to evaluate the safety and efficacy of etoposide in patients with the 2019 novel coronavirus (COVID-19) infection. Randomization will be performed with a 3:1 allocation ratio. Treatment will be comprised of etoposide administered intravenously at a dose of 150 mg/m2 on Days 1 and 4 in patients with COVID-19 infection meeting eligibility criteria. Subsequent doses of etoposide will be allowed if the investigator and treating physician believe the patient had clinical benefit from etoposide therapy but subsequently has evidence of recurrent clinical deterioration. Subjects randomized to control will receive standard of care treatment. No placebo will be used.

Viruxal Oral and Nasal Spray is a Class I CE marked medical device manufactured by Kerecis hf (the "Device"). A double blind clinical trial will be conducted to evaluate the Device against placebo in COVID-19 positive, symptomatic patients in Iceland. Immediate access to COVID-19 patients is available through a well-organized COVID-19 outpatient follow-up clinic. Up to 128 patients with mild to moderate symptoms of COVID-19 will be recruited (so called "higher end of the low risk group"). These patients will be positive for COVID-19, be symptomatic with upper respiratory symptoms, but without involvement of the entire respiratory system. The patients will be randomized to receive treatment with the Study Device or to receive placebo. 64 patients will be randomized into the Study Device group and 64 patients into the Control group. Patients will administer Study Device or Control for 14 days and will have their symptoms recorded until no further symptoms are reported, up to a maximum of 28 days follow-up.

The outbreak at covid-19 is caused by the SARS-CoV-2 virus. This virus can be responsible for severe respiratory failure but also for extra-respiratory organ dysfunctions associated with severe inflammatory stress. The endothelium is an important structure of the blood vessels and is implicated in the organ failure of many patients admitted in intensive care units. It could be affected by the virus and its alteration may explain the organ dysfunction of covid-19 ICU patients as well as the thrombotic processes frequently obstructed in this infection.

In the SAVE study patients with lower respiratory tract infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at high risk for progression to serious respiratory failure will be detected using the suPAR biomarker. They will begin early treatment with anakinra in the effort to prevent progression in serious respiratory failure.

The COVID-19 emerging disease due to a novel coronavirus (SARS-CoV-2), started in Wuhan, China, last December, 2019. In the past three months, the virus has spread rapidly worldwide to reach the pandemic threshold. Research has since been carried out and is intensifying in order to describe the clinical characteristics of infected patients, to identify the prognostic factors of acute respiratory distress syndrome [ARDS] and the death; and to assess the effectiveness of new antivirals and therapeutic strategies to treat COVID-19. Treatments currently being investigated include: - Potentially effective treatments: (hydroxy)chloroquine, Remdesivir, Lopinavir, Ritonavir +/- IFN-ß-1a (currently evaluated in the European discovery trial), methylprednisolone in patients with ARDS; - Potentially harmful treatments: antihypertensives such as converting enzyme inhibitors and angiotensin receptor antagonists. We made the hypothesis that (1) patients receiving ARBs or ACEi's have a higher risk to present a serious COVID-19 infection disease and (2) patients receiving synthetic AMD (e.g. HCQ and CQ) have a lower risk to present a serious covid19 infection disease. Using data from the French insurance health database (SNDS) and hospital discharge database (PMSI), our objectives are - Main objective: To assess the risk of moderate to serious COVID-19 infections in patients using synthetic anti-malarial drugs (AMD) or anti-hypertensive drugs (Angiotensin receptor-blocking/Angiotensin-converting-enzyme inhibitors). - Secondary objective : To examine the risk of moderate to serious COVID-19 infections according of age, sex, co-morbidities, level of exposure of AMD, geographical locations and underlying comorbidities. This in order to: - To prevent moderate to serious COVID-19 infections in at-risk population (diabetes, elderly, respiratory failure population) using synthetic AMD. - To prevent moderate to serious COVID-19 infections in at-risk population stopping angiotensin receptor-blocking and angiotensin-converting-enzyme inhibitors.

The COVID-19 outbreak is associated with a surge in ICU bed requirement and substantial mortality (estimated between 0.5% and 1%). Admission in the intensive care unit (ICU) and need for mechanical ventilation is reportedly associated with an estimated hospital mortality of more than 30%. Furthermore, the surge in ICU bed requirement is a worldwide-shared issue, leading to sub-optimal ICU management. In acute respiratory failure due to COVID-19-related pneumonia, vasoplegia with vascular enlargement inside the lung lesions and dilation of small vessels seen on chest CT scan largely account for severe hypoxemia whose physiological response is hyperventilation leading to hypocapnia. Almitrine, initially described to reduce intrapulmonary shunt by enhancement of hypoxic pulmonary vasoconstriction in combination with inhaled nitric oxide (iNO), redistributes pulmonary blood flow from shunt areas to lung units with normal ventilation/perfusion (VA/Q) ratio. Low dose of intravenous almitrine (2 µg.kg-1.min-1) alone also improves oxygenation (without combination with iNO) by selective pulmonary vasoconstriction of precapillary pulmonary arteries perfusing lung areas exposed to a hypoxic challenge with a slight increase in mean arterial pulmonary. Therefore, our hypothesis is that 5 days of low dose of almitrine therapy may improve the ventilation-perfusion (VA/Q) ratio at a relatively early stage of this specific lung disease and limit respiratory worsening and subsequent need for mechanical ventilation.

Given the possible risks and complications of a comorbidity between psychiatric disorder and coronavirus disease 2019 (COVID-19), it seems particularly important to specify the impact of the COVID-19 pandemic in patients with psychiatric disorders and suspected of infection, hospitalized in a specific unit, at the psychiatric, somatic and pharmacological level.

Three hundred healthcare workers with mild symptoms for Covid-19 will be followed during three months. Each two weeks, serological tests will be performed. Re-infection will be monitored by saliva-swabs.