Evaluation of the efficacy and safety of icatibant and C1 esterase/kallikrein inhibitor in severe COVID-19: study protocol for a three-armed randomized controlled trial

Autor: Eli Mansour, Raisa G. Ulaf, Milena Monfort-Pires, Sergio Dertkigil, Tatiana Benaglia, Licio A. Velloso, Luciana C. Ribeiro, Maria Luiza Moretti, Jose Carlos de Lima-Junior, Bruna Bombassaro, Rafael Pimentel Maia, Eliana P. Araújo, Thyago A. Nunes, A. F. Bernardes, Flavia Fagundes Bueno, Thiago Martins Santos, Plínio Trabasso, Antonio Luis Eiras Falcão, Andre C. Palma, Rachel P Dertkigil
Jazyk: angličtina
Rok vydání: 2021
Předmět:
medicine.medical_treatment
Medicine (miscellaneous)
ACE2
Pharmacology
C1 esterase inhibitor
Severity of Illness Index
law.invention
Study Protocol
chemistry.chemical_compound
0302 clinical medicine
Randomized controlled trial
Icatibant
law
Bradykinin B2 Receptor Antagonists
Antithrombotic
Medicine
Pharmacology (medical)
030212 general & internal medicine
Randomized Controlled Trials as Topic
0303 health sciences
lcsh:R5-920
Treatment Outcome
Injections
Intravenous
Drug Therapy
Combination
Kallikreins
Angiotensin-Converting Enzyme 2
Respiratory Insufficiency
lcsh:Medicine (General)
Complement C1 Inhibitor Protein
Brazil
Adult
Side effect
Injections
Subcutaneous
Bradykinin
Drug Administration Schedule
03 medical and health sciences
Clinical Trials
Phase II as Topic
Humans
Renal replacement therapy
030304 developmental biology
Pneumonitis
SARS-CoV-2
business.industry
COVID-19
Pneumonia
medicine.disease
COVID-19 Drug Treatment
Clinical trial
chemistry
business
Zdroj: Trials, Vol 22, Iss 1, Pp 1-13 (2021)
Trials
ISSN: 1745-6215
Popis: Background SARS-CoV-2, the virus that causes COVID-19, enters the cells through a mechanism dependent on its binding to angiotensin-converting enzyme 2 (ACE2), a protein highly expressed in the lungs. The putative viral-induced inhibition of ACE2 could result in the defective degradation of bradykinin, a potent inflammatory substance. We hypothesize that increased bradykinin in the lungs is an important mechanism driving the development of pneumonia and respiratory failure in COVID-19. Methods This is a phase II, single-center, three-armed parallel-group, open-label, active control superiority randomized clinical trial. One hundred eighty eligible patients will be randomly assigned in a 1:1:1 ratio to receive either the inhibitor of C1e/kallikrein 20 U/kg intravenously on day 1 and day 4 plus standard care; or icatibant 30 mg subcutaneously, three doses/day for 4 days plus standard care; or standard care alone, as recommended in the clinical trials published to date, which includes supplemental oxygen, non-invasive and invasive ventilation, antibiotic agents, anti-inflammatory agents, prophylactic antithrombotic therapy, vasopressor support, and renal replacement therapy. Discussion Accumulation of bradykinin in the lungs is a common side effect of ACE inhibitors leading to cough. In animal models, the inactivation of ACE2 leads to severe acute pneumonitis in response to lipopolysaccharide (LPS), and the inhibition of bradykinin almost completely restores the lung structure. We believe that inhibition of bradykinin in severe COVID-19 patients could reduce the lung inflammatory response, impacting positively on the severity of disease and mortality rates. Trial registration Brazilian Clinical Trials Registry Universal Trial Number (UTN) U1111-1250-1843. Registered on May/5/2020.
Databáze: OpenAIRE
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