TY  - JOUR
A1  - Schmid, Benedikt
A1  - Kredel, Markus
A1  - Ullrich, Roman
A1  - Krenn, Katharina
A1  - Lucas, Rudolf
A1  - Markstaller, Klaus
A1  - Fischer, Bernhard
A1  - Kranke, Peter
A1  - Meybohm, Patrick
A1  - Zwißler, Bernhard
A1  - Frank, Sandra
T1  - Safety and preliminary efficacy of sequential multiple ascending doses of solnatide to treat pulmonary permeability edema in patients with moderate-to-severe ARDS - a randomized, placebo-controlled, double-blind trial
JF  - Trials
N2  - Background

Acute respiratory distress syndrome (ARDS) is a complex clinical diagnosis with various possible etiologies. One common feature, however, is pulmonary permeability edema, which leads to an increased alveolar diffusion pathway and, subsequently, impaired oxygenation and decarboxylation. A novel inhaled peptide agent (AP301, solnatide) was shown to markedly reduce pulmonary edema in animal models of ARDS and to be safe to administer to healthy humans in a Phase I clinical trial. Here, we present the protocol for a Phase IIB clinical trial investigating the safety and possible future efficacy endpoints in ARDS patients.

Methods

This is a randomized, placebo-controlled, double-blind intervention study. Patients with moderate to severe ARDS in need of mechanical ventilation will be randomized to parallel groups receiving escalating doses of solnatide or placebo, respectively. Before advancing to a higher dose, a data safety monitoring board will investigate the data from previous patients for any indication of patient safety violations. The intervention (application of the investigational drug) takes places twice daily over the course of 7 days, ensued by a follow-up period of another 21 days.

Discussion

The patients to be included in this trial will be severely sick and in need of mechanical ventilation. The amount of data to be collected upon screening and during the course of the intervention phase is substantial and the potential timeframe for inclusion of any given patient is short. However, when prepared properly, adherence to this protocol will make for the acquisition of reliable data. Particular diligence needs to be exercised with respect to informed consent, because eligible patients will most likely be comatose and/or deeply sedated at the time of inclusion.

Trial registration

This trial was prospectively registered with the EU Clinical trials register (clinicaltrialsregister.eu). EudraCT Number: 2017-003855-47.
KW  - acute respiratory distress syndrome
KW  - solnatide
KW  - extravascular lung water
KW  - pulmonary edema
KW  - critical care
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258783
VL  - 22
IS  - 1
ER  - 
TY  - JOUR
A1  - Notz, Quirin
A1  - Herrmann, Johannes
A1  - Schlesinger, Tobias
A1  - Helmer, Philipp
A1  - Sudowe, Stephan
A1  - Sun, Qian
A1  - Hackler, Julian
A1  - Roeder, Daniel
A1  - Lotz, Christopher
A1  - Meybohm, Patrick
A1  - Kranke, Peter
A1  - Schomburg, Lutz
A1  - Stoppe, Christian
T1  - Clinical Significance of Micronutrient Supplementation in Critically Ill COVID-19 Patients with Severe ARDS
JF  - Nutrients
N2  - The interplay between inflammation and oxidative stress is a vicious circle, potentially resulting in organ damage. Essential micronutrients such as selenium (Se) and zinc (Zn) support anti-oxidative defense systems and are commonly depleted in severe disease. This single-center retrospective study investigated micronutrient levels under Se and Zn supplementation in critically ill patients with COVID-19 induced acute respiratory distress syndrome (ARDS) and explored potential relationships with immunological and clinical parameters. According to intensive care unit (ICU) standard operating procedures, patients received 1.0 mg of intravenous Se daily on top of artificial nutrition, which contained various amounts of Se and Zn. Micronutrients, inflammatory cytokines, lymphocyte subsets and clinical data were extracted from the patient data management system on admission and after 10 to 14 days of treatment. Forty-six patients were screened for eligibility and 22 patients were included in the study. Twenty-one patients (95%) suffered from severe ARDS and 14 patients (64%) survived to ICU discharge. On admission, the majority of patients had low Se status biomarkers and Zn levels, along with elevated inflammatory parameters. Se supplementation significantly elevated Se (p = 0.027) and selenoprotein P levels (SELENOP; p = 0.016) to normal range. Accordingly, glutathione peroxidase 3 (GPx3) activity increased over time (p = 0.021). Se biomarkers, most notably SELENOP, were inversely correlated with CRP (r\(_s\) = −0.495), PCT (r\(_s\) = −0.413), IL-6 (r\(_s\) = −0.429), IL-1β (r\(_s\) = −0.440) and IL-10 (r\(_s\) = −0.461). Positive associations were found for CD8\(^+\) T cells (r(_s\) = 0.636), NK cells (r\(_s\) = 0.772), total IgG (r\(_s\) = 0.493) and PaO\(_2\)/FiO\(_2\) ratios (r\(_s\) = 0.504). In addition, survivors tended to have higher Se levels after 10 to 14 days compared to non-survivors (p = 0.075). Sufficient Se and Zn levels may potentially be of clinical significance for an adequate immune response in critically ill patients with severe COVID-19 ARDS.
KW  - acute respiratory distress syndrome
KW  - selen
KW  - zinc
KW  - critical care
KW  - oxidative stress
KW  - nutrient supplementation
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241112
SN  - 2072-6643
VL  - 13
IS  - 6
ER  -