Almitrine and COVID-19 Related Hypoxemia

NCT04380727 | Completed

• 1 other identifier: 2020PI080_2
• Study Type: observational
• Target: 17
• Locations: 1 country
• Sites: 1

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).

Conditions

COVID-19; Hypoxic Respiratory Failure

Keywords

Hypoxic pulmonary vasoconstriction; Prone position; intra-pulmonary shunt; SARS-CoV-2

Outcome Measures

Primary Outcomes (2)

• Changes from baseline PaO2 (mmHg)

  Partial pressure of oxygen in arterial blood

  45 minutes after almitrine infusion

• Changes from baseline ScvO2 (%)

  central venous oxygen saturation

  baseline and 45 minutes after almitrine infusion

Secondary Outcomes (2)

• Changes from baseline PaO2 (mmHg)

  8 hours

• Changes from baseline ScvO2 (%)

  8 hours

Study Arms (2)

Almitrine

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..

Control

To eliminate the eventuality of a spontaneous evolution of hypoxia, these patients were matched to control COVID-19 patients treated without almitrine (time control).

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Between March16 and April 20, 2020, COVID-19 patients referred to ICU age, gender, BMI, Hb The recorded parameters were: the ventilatory settings unchanged along the protocol, including FiO2, PEEP level, tidal volume (VT), peak inspiratory pressure, plateau pressure; haemoglobin concentration, blood gases simultaneously sampled on the arterial catheter and on the central catheter to assess central venous oxygen saturation SvcO2, and arterial lactate, right atrial pressure; cardiac output when possible (Mostcare®, Vygon, Ecouen, France).

You may qualify if:

• a positive RT- PCR,
• a highly suggestive thoracic CTScan, and
• a severe hypoxemia leading to intubation for less than 3 days
• mechanically ventilated at FiO2 1 with a severe intrapulmonary shunt during their early phase
• Group : patient who has been treated with almitrine (4 mcg/kg/min iv almitrine bismesylate (Vectarion®, Servier Laboratory, France) then 12 mcg/kg/min infusion rate) during their hospital treatment.

You may not qualify if:

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

Sponsors & Collaborators

• Central Hospital, Nancy, France: lead

Study Sites (1)

Centre Hospitalier Universitaire NANCY

Vandœuvre-lès-Nancy, 54511, France

Location

Related Publications (5)

• Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30.

  PMID: 32007143 BACKGROUND

• Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.

  PMID: 32171076 BACKGROUND

• Gattinoni L, Coppola S, Cressoni M, Busana M, Rossi S, Chiumello D. COVID-19 Does Not Lead to a "Typical" Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2020 May 15;201(10):1299-1300. doi: 10.1164/rccm.202003-0817LE. No abstract available.

  PMID: 32228035 BACKGROUND

• Payen DM, Gatecel C, Plaisance P. Almitrine effect on nitric oxide inhalation in adult respiratory distress syndrome. Lancet. 1993 Jun 26;341(8861):1664. doi: 10.1016/0140-6736(93)90801-m. No abstract available.

  PMID: 8100027 BACKGROUND

• B'chir A, Mebazaa A, Losser MR, Romieu M, Payen D. Intravenous almitrine bismesylate reversibly induces lactic acidosis and hepatic dysfunction in patients with acute lung injury. Anesthesiology. 1998 Oct;89(4):823-30. doi: 10.1097/00000542-199810000-00005.

  PMID: 9777998 BACKGROUND

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Marie Reine LOSSER, MD, PhD

  Central Hospital, Nancy, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2020
• First Posted: May 8, 2020
• Study Start: March 20, 2020
• Primary Completion: April 14, 2020
• Study Completion: April 25, 2020
• Last Updated: July 30, 2020

Record last verified: 2020-07

Locations

FR (1)