Xanthohumol as an Adjuvant Therapy in Critically Ill COVID-19 Patients

Study Overview
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Brief Summary
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It has been well documented that coronavirus COVID-19 disease is associated with massive inflammatory response and cytokine storm. Several medications have been used to ameliorate COVID-19-related inflammation. Xanthohumol, a natural medication extracted from hop cones, possesses strong anti-inflammatory properties and can reduce the severity of inflammatory response. The aim of this study is to analyze the effect of Xanthohumol on clinical course, inflammatory response and outcome in patients admitted to the ICU due to COVID-related acute respiratory failure with an oxygenation index (PaO2/FiO2) less than 150.

Detailed Description
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Xanthohumol inhibits proinflammatory pathways in different independent mechanisms. Ir inhibits farnesoid X receptor activity, and reduces the synthesis and release of different proinflammatory cytokines such as IL-1β, IL-6, IL-8, IL-12p70, TNFα and interferon γ. The pathomechanism of its anti-inflammatory activity is associated with the suppression of nuclear factor-kappa B. Additionally, Xanthohumol inhibits inflammatory-induced endothelial disorders, which are associated with an improvement in blood velocity and a reduction in the risk of arterial thrombosis, especially in pulmonary arteries. An increase in proinflammatory release, known as cytokine storm, as well as increased incidences of vascular thrombosis, are observed in coronavirus infection. Hence, Xanthohumol may reduce the severity of the clinical course in COVID-19 patients.

Official Title
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Humulus Lupus Extract Rich in Xanthohumol Improves Clinical Course in Critically Ill COVID-19 Patients

Conditions
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COVID-19 Respiratory Infection

Intervention / Treatment
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* Biological: Xanthohumol - prenylated chalcone extracted from female inflorescences of hop cones (Humulus lupus). Hop-RXn™, BioActive-Tech Ltd, Lublin, Poland; http://xanthohumol.com.pl/


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of COVID-19 with acute respiratory failure (PaO2/FiO2 below 150). Exclusion Criteria: History of chronic cardiovascular, liver or/and kidney diseases. History of chronic pulmonary diseases with prolonged oxygen supplementation or domestic mechanical ventilation. Pregnant women, Neoplastic diseases, Immunologic diseases Patients received immunomodulatory treatment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Patients were randomized in a double-blind, placebo-controlled fashion into two groups using sealed envelopes
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group Xn<br>Patients who received extract from Humulus lupus L rich in Xanthohumol (Hop-RXn™, BioActive-Tech Ltd, Lublin, Poland; http://xanthohumol.com.pl/) as an adjuvant therapy. Based on pharmacokinetics and bioactivity, Xn was administered enterally three times a day every 8 hours at a dose of 1.5 mg/kg body weight (4.5 mg/kg body weight/day) for 7 days. The first dose of Xn was administered within 4 hours after admission to the ICU. | Biological: Xanthohumol - prenylated chalcone extracted from female inflorescences of hop cones (Humulus lupus). Hop-RXn™, BioActive-Tech Ltd, Lublin, Poland; http://xanthohumol.com.pl/<br>* The appropriate dose of Xanthohumol was solved in 1 mL of propylene glycol<br>|
| Placebo Comparator: Group C<br>Patients who received 0.9% NaCl at the oral volume 1 mL (similar to Xn volume) three times a day every 8 hours. The first dose of Xn was administered within 4 hours after admission to the ICU. | Biological: Xanthohumol - prenylated chalcone extracted from female inflorescences of hop cones (Humulus lupus). Hop-RXn™, BioActive-Tech Ltd, Lublin, Poland; http://xanthohumol.com.pl/<br>* The appropriate dose of Xanthohumol was solved in 1 mL of propylene glycol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Xanthohumol reduces coronavirus-induced inflammatory response | Xanthohumol possesses strong anti-inflammatory properties. It can reduce the production and secretion of pro-inflammatory cytokines. Additionally, it inhibits inflammatory-induced endothelial dysregulation and exerting antiangiogenic and anti-inflammatory effects. | one week after regular supplementation | 
| Xanthohumol improves clinical course in critically ill COVID-19 patients | Reduction the severity of inflammatory response should affect clinical course. Strong anti-inflammatory treatment can reduce a risk of poor outcome. | 28 days mortality |