COVID-19 Clinical Trials and Expanded Access

Rationale Many patients with coronavirus disease (COVID-19) need hospital admission for oxygen supplementation. A substantial number of patients need intensive care unit (ICU) admission for escalation of care. ICU doctors and nurses are struggling to provide the best care for patients with COVID-19. Practice of adjunctive and supportive treatments remains uncertain. Objective To determine and compare practice of adjunctive and supportive treatments for COVID-19 in the Netherlands, and to determine their independent associations with outcome. Hypotheses Practice of adjunctive and supportive treatments for COVID-19 varies substantially. Adjunctive and supportive treatments have an independent association with outcome in ICU patients with COVID-19. Study design National/international, multicenter, retrospective observational study. Study population Intensive care unit (ICU) patients with COVID-19. Methods In this study we will collect data on diverse treatments during the first 28 days in ICU, including (a) the types of oxygen support* and awake prone positioning; (b) the types of ventilatory support, (c) rescue therapies for refractory hypoxemia during invasive ventilation (prone positioning, ventilator adjustments, continuous muscle paralysis, and extracorporeal membrane oxygenation); (d) adjunctive treatments, including thromboprophylaxis and anticoagulation, antiviral and immunomodulating therapies, and (e) experimental supportive treatments. Outcomes include duration of each adjunctive treatment, duration of ventilation, incidence of tracheostomy, duration of stay in ICU and mortality until day 90. Study endpoints A combination of adjunctive treatments, including types of oxygen support, ventilatory support and rescue therapies for refractory hypoxemia during invasive ventilation (primary), other adjunctive and supportive treatments, tracheostomy rate; duration of ventilation and ventilator-free days and alive at day 28 (VFD-28), duration of ICU and hospital stay, and ICU, hospital and 90-day mortality. Nature and extent of the burden and risks associated with participation, benefit and group relatedness Retrospective collection of data regarding adjunctive treatments, and clinical endpoints is without risk for ICU patients. *In a subset of patients we will collect granular data (every two hours) regarding oxygenation (FiO2, inspiratory tidal volume, air flow, respiratory rate, SpO2, PaO2, and PEEP) over the first 2 full calendar days of ICU admission. The primary endpoint of this sub-analysis will be the amount of oxygen used with different respiratory support interventions. The statistical analysis plan for the analysis of these data that were collected in two ICUs that participated in the national study, and one additional ICU in Spain is uploaded in the document section (filename Statistical Analysis Plan PROXY-COVID)

The primary aim of the study is to evaluate the safety and tolerability of open-label ST266 given to subjects with confirmed COVID-19 infection through IV administration once a day of 5 consecutive days.

The current study will be a randomized controlled trial (RCT) investigating an adapted online Mindfulness-Based Stress Reduction (MBSR) program versus daily online self-help mindfulness exercises, in preventing incident/prevalent psychopathology in healthcare workers allocated to work with COVID-19 patients. Outcome measures include depression, anxiety, somatoform symptoms, post-traumatic stress, insomnia, substance abuse, post-traumatic growth and positive mental health. The study also aims to explore possible working mechanisms such as perseverative thinking, mindfulness skills and self-compassion. The study will have a follow-up duration of 7 months from baseline.

During the COVID-19 (corona virus) pandemic the research arena has had to rapidly adapt and change in order to facilitate and deliver research. The UK (United Kingdom) government and Public Health England have stressed the importance of such research to find solutions to treating, preventing and stopping the spread of COVID-19. Due to national and international 'lock down restrictions' delivering research in care home settings has become even more challenging. The adaptations to conducting consultations have relied heavily on the use of technology, for example video calling, telephone, email, and teleconferencing. It is suggested that the use of technology in care home settings is already a barrier to effective research delivery. Nevertheless, as care home residents are a vulnerable group, it is critical to include these groups in research in order to enable improved and evidence-based care and their access to new and emerging treatments. This study aims to assess the opinions and experiences of key stakeholders to identify barriers, and enable better facilitation of research in these settings during and post pandemic.

The new coronavirus 2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO), due to the alarming levels of spread, severity and inaction. Dealing with COVID-19 must be done on different fronts, such as mitigation, treatment and prevention. Therefore, strategies and therapies that can help reduce the COVID-19 rate of contamination are still important alternatives at this time of the pandemic. The Advanced Penetration Technology™ (APT™) is intellectual property owned by Patient Focused Tele-Health, LLC, a Rockwall, Texas based company. The company's focus is improving over-the-counter (OTC) topical formulations, allowing consumers better therapeutic outcomes with non-prescription medications. The Advanced Penetration Technology™ (APT™) is a patent-pending, proprietary transdermal dual carrier formulation. This formulation provides improved dermal penetration and efficacy of topical API's. Additionally, the APT™ imparts both a mechanical and biochemical effect on the microbe/fungal cell walls providing a highly effective method of destruction of microbes. These unique properties impart the broad spectrum anti-viral capability to the APT™ Tetracycline 3% formulation, breaking barriers in pharmacology and virology. The topical formulation APT™ Tetracycline 3% formulation (APT ™ T3X), is a FDA registered, Non-Prescription product. This formulation is used in an off label manner as an intranasal application for prevention of COVID-19 and other viruses. The APT™ T3X as a topical application will penetrate through and into the mucus layer and deeper. This barrier of coverage will provide a mitigation effect to decrease the viral load of exposure and infection. The efficacy of APT™ T3X is due to disrupting the lipid envelope in seconds, hence neutralizing the virus. Previous tests were performed with APT™ T3X and the results found were promising. However, these tests were performed only in vitro and clinical studies demonstrating the ability of the APT™ T3X to decrease viral exposure and contamination by COVID-19 are necessary to confirm the possible prophylactic effect, allowing the formulation to be widely distributed to the general population. Therefore, the aim of this project is to evaluate the efficacy of the APT™ T3X compared to placebo to decrease COVID-19 contamination rate in humans.

To evaluate the value-based effectiveness of the implementation of TMH Extended post anaesthetic care in PACU during COVID-19 pandemics by an institutional matched case-control and quantitative survey study Two ordinary recovery beds were converted to an overnight intensive recovery ("Extended post-anesthetic care in PACU") within the operating theatre complex of Tuen Mun Hospital during COVID-19 pandemics, in an attempt to free the ICU bed and resources from postoperative patients. This study was designed to evaluate the efficacy and staff perceptions towards the abrupt implementation of TMH extended post-anesthetic care in PACU by mobilization of the existing OT resources to cope with the COVID-19 emergency situations. The value-based analysis would look into the implementation effectiveness in twofold: 1) the clinical efficacy using a case-control audit on clinical outcomes and 2) the staff acceptance by means of the staff attitudes survey. Hopefully, this would provide a multi-perspective evaluation of the implementation strategies and aid planning of new services in the future.

The aim of this study is to compare the SARS-CoV-2 detection rate using either a Saliva, oropharyngeal swabs or nasopharyngeal swab method for specimen collection.

The investigators hypothese that lung involvement due to COVID-19 may cause structural changes in the lung in the long term. In this study the effects of structural changes in the lung on pulmonary function tests, exercise capacity and quality of life will be examined.

This is a multicenter open-label randomized study for the early treatment of pneumonia due to SARS-COV2 with transfusion of convalescent plasma. Patients with pneumonia due to SARS-CoV-2 will be randomized to receive or not convalescent plasma collected by recovered patients with previous diagnosis of COVID19

The main clinical manifestation associated with SARS-CoV-2 infection is an influenza-like illness that follows the infection of the respiratory tract. In a few percent of infected people, inflammation of the lungs leads to severe pneumonia that requires hospitalization, in intensive care units for the more severe cases. Despite intensive care, a fatal outcome occurs in 6% and 12% of women and men over 80 years of age hospitalized for severe COVID, respectively. Factors associated with a higher risk of death in patients with SARS-CoV-2 include age and low circulating lymphocyte counts. Significant lymphopenia is indeed frequently observed in patients with severe COVID-19 and both phenotypic and functional changes in antiviral T cells have been correlated with the severity of COVID-19. The thymus, the organ that produces T lymphocytes, undergoes progressive physiological involution with age. However, in the elderly, rare cases of thymic hyperplasia are reported in autoimmune diseases or cancers, or are observed in response to deep lymphopenia, whether or not associated with sepsis. This cohort of patients treated for a SARS-CoV-2 infection could allow to better understand the role of the thymus in this pathology.