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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
Sponsor:
Information provided by (Responsible Party):
Central Hospital, Nancy, France

Tracking Information
First Submitted Date April 28, 2020
First Posted Date May 8, 2020
Last Update Posted Date July 30, 2020
Actual Study Start Date March 20, 2020
Actual Primary Completion Date April 14, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: May 7, 2020)
  • 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
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: May 7, 2020)
  • 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
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Almitrine and COVID-19 Related Hypoxemia
Official Title Almitrine and Severe COVID-19 Patients in ICU [Almitrine et Patients COVID-19 en Reanimation (French)]
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 Type Observational [Patient Registry]
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration 2 Months
Biospecimen Not Provided
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).
Condition
  • COVID-19
  • Hypoxic Respiratory Failure
Intervention Not Provided
Study Groups/Cohorts
  • 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).
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: May 7, 2020)
17
Original Actual Enrollment Same as current
Actual Study Completion Date April 25, 2020
Actual Primary Completion Date April 14, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria :

  • 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.

Control group : Matched COVID-19 patients, on gender, age, BMI and duration of mechanical ventilation, with serial measurements corresponding to the duration of almitrine testing (8 hours), with same inclusion and exclusion criteria.

Exclusion Criteria:

  • the presence of an acute cor-pulmonale on the trans-thoracic 2D Echo-Doppler
  • abnormal liver function tests
  • hyperlactatemia
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries France
Removed Location Countries  
 
Administrative Information
NCT Number NCT04380727
Other Study ID Numbers 2020PI080_2
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Plan Description: Collaborative register on COVID-19 having benn treated with almitrine
Responsible Party Central Hospital, Nancy, France
Study Sponsor Central Hospital, Nancy, France
Collaborators Not Provided
Investigators
Principal Investigator: Marie Reine LOSSER, MD, PhD Central Hospital, Nancy, France
PRS Account Central Hospital, Nancy, France
Verification Date July 2020