Almitrine and COVID-19 Related Hypoxemia

Completed

• Conditions: COVID-19; Hypoxic Respiratory Failure

• Registration Number: NCT04380727
• Lead Sponsor: Central Hospital, Nancy, France

Brief Summary

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).

Detailed Description

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 Timeline

• Study Start: 2020-03-20
• Primary Completion: 2020-04-14
• Study Completion: 2020-04-25
• Study First Submitted: 2020-04-28
• Study First Submitted QC: 2020-05-07
• Study First Posted: 2020-05-08
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-29
• Last Update Posted: 2020-07-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

Not provided

Exclusion Criteria

• the presence of an acute cor-pulmonale on the trans-thoracic 2D Echo-Doppler
• abnormal liver function tests
• hyperlactatemia

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Changes from baseline PaO2 (mmHg)	45 minutes after almitrine infusion	Partial pressure of oxygen in arterial blood
Changes from baseline ScvO2 (%)	baseline and 45 minutes after almitrine infusion	central venous oxygen saturation

Secondary Outcome Measures

Name	Time	Method
Changes from baseline ScvO2 (%)	8 hours	central venous oxygen saturation
Changes from baseline PaO2 (mmHg)	8 hours	partial pressure of oxygen in arterial blood

Trial Locations

Locations (1)

Centre Hospitalier Universitaire NANCY; 🇫🇷 Vandoeuvre-les-Nancy, France