Almitrine and COVID-19 Related Hypoxemia
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|ClinicalTrials.gov Identifier: NCT04380727|
Recruitment Status : Completed
First Posted : May 8, 2020
Last Update Posted : July 30, 2020
In severe COVID-19 pulmonary failure, the profound hypoxemia is mainly related to pulmonary vasodilation with altered hypoxic pulmonary vasoconstriction (HPV). Besides prone positioning, other non-ventilatory strategies may reduce the intrapulmonary shunt. This study has investigated almitrine, a pharmacological option used in standard care to improve oxygenation.
A case control series of mechanically ventilated confirmed COVID-19 patients was recorded.
At stable ventilatory settings, consecutive patients received two doses of almitrine (4 and 12 mcg/kg/min) at 30-45 min interval each, and were compared to 7 "control" COVID-matched patients conventionally treated.
The end-point was the reduction of intra-pulmonary shunt, with an increase in partial pressure of arterial oxygen (PaO2) and central venous oxygen saturation (ScvO2).
|Condition or disease|
|COVID-19 Hypoxic Respiratory Failure|
The clinical presentation of COVID-19 disease is heterogenous, ranging from no symptoms to severe acute respiratory failure (ARF), which may have a poor prognosis. A severe hypoxemia is associated with preserved respiratory mechanical properties, in particular the pulmonary system compliance.
The hypoxia during the early phase seems to mainly result from an important ventilation/perfusion (VA/Q) mismatch associated with an altered pulmonary vasoconstriction. The "protective" mechanism called hypoxic pulmonary vasoconstriction (HPV) normally reduces the blood flow in poorly or non-ventilated areas towards aerated zones leading to reduce the (VA/Q) mismatch. HPV seems poorly functional in COVID-19 severe patients in absence of "cor pulmonale".
According to the French National agency for Drug Security (ANSM, Paris, France), only iv almitrine is indicated for hypoxic acute respiratory failure as Drug of Major Therapeutic Interest. This molecule is a routine option in the treatment strategy of severe hypoxemia.
The investigators studied COVID-19 patients mechanically ventilated at FiO2 1 with a severe intrapulmonary shunt during their early phase. The emergency conditions and the acute high inflow of patients to ICU impeded the design of a randomized control trial. To eliminate the eventuality of a spontaneous evolution of hypoxia, these patients will be compared with control-matched COVID patients treated conventionally.
|Study Type :||Observational [Patient Registry]|
|Actual Enrollment :||17 participants|
|Target Follow-Up Duration:||2 Months|
|Official Title:||Almitrine and Severe COVID-19 Patients in ICU [Almitrine et Patients COVID-19 en Reanimation (French)]|
|Actual Study Start Date :||March 20, 2020|
|Actual Primary Completion Date :||April 14, 2020|
|Actual Study Completion Date :||April 25, 2020|
Administration of 4 mcg/kg/min iv almitrine bismesylate (Vectarion®, Servier Laboratory, France), over 30-45 min followed by 12 mcg/kg/min infusion rate. Because of a shortage of drug store at national level, a protocol using continuous infusion was not considered. Some patients may receive the drug for 36 hours depending on availability..
To eliminate the eventuality of a spontaneous evolution of hypoxia, these patients were matched to control COVID-19 patients treated without almitrine (time control).
- Changes from baseline PaO2 (mmHg) [ Time Frame: 45 minutes after almitrine infusion ]Partial pressure of oxygen in arterial blood
- Changes from baseline ScvO2 (%) [ Time Frame: baseline and 45 minutes after almitrine infusion ]central venous oxygen saturation
- Changes from baseline PaO2 (mmHg) [ Time Frame: 8 hours ]partial pressure of oxygen in arterial blood
- Changes from baseline ScvO2 (%) [ Time Frame: 8 hours ]central venous oxygen saturation
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04380727
|Centre Hospitalier Universitaire NANCY|
|Vandoeuvre-les-Nancy, France, 54511|
|Principal Investigator:||Marie Reine LOSSER, MD, PhD||Central Hospital, Nancy, France|