COVID-19NCT04380727
Almitrine and COVID-19 Related Hypoxemia
An observational study of COVID-19 and Hypoxic Respiratory Failure, run by Central Hospital, Nancy, France at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19, Hypoxic Respiratory Failure
- Type of treatment
- Injection or infusion
- How many people
- 17 participants
- Where
- 1 siteFrance
- Study dates
- 20 Mar 2020to 25 Apr 2020
- How long will I take part?
- 2 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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).
Who may be able to join
- 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.
Who cannot join
- the presence of an acute cor-pulmonale on the trans-thoracic 2D Echo-Doppler
- abnormal liver function tests
- hyperlactatemia
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Almitrine and Severe COVID-19 Patients in ICU [Almitrine et Patients COVID-19 en Reanimation (French)]
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.
Read more
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).
Read the 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.
- Conditions
- COVID-19, Hypoxic Respiratory Failure
- Keywords
- Hypoxic pulmonary vasoconstriction, Prone position, intra-pulmonary shunt, SARS-CoV-2
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes from baseline PaO2 (mmHg)
Partial pressure of oxygen in arterial blood
Measured: 45 minutes after almitrine infusion
Changes from baseline ScvO2 (%)
central venous oxygen saturation
Measured: baseline and 45 minutes after almitrine infusion
Secondary outcomes (2)
Changes from baseline PaO2 (mmHg)
partial pressure of oxygen in arterial blood
Measured: 8 hours
Changes from baseline ScvO2 (%)
central venous oxygen saturation
Measured: 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2020
- Study start20 Mar 2020
- Primary completion14 Apr 2020
- Study completion25 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by Central Hospital, Nancy, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 17 participants (actual)
- Target duration
- 2 Months
Sponsor and investigators
- Lead sponsor
- Central Hospital, Nancy, France
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marie Reine LOSSER, MD, PhD, Principal investigator, Central Hospital, Nancy, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04380727
- Sponsor's protocol ID
- 2020PI080_2
- Status last verified
- Jul 2020
- First submitted
- 28 Apr 2020
- Last updated
- 30 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Collaborative register on COVID-19 having benn treated with almitrine
Publications
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.
PubMed 32007143Zhou 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.
PubMed 32171076Gattinoni 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.
PubMed 32228035Payen 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.
PubMed 8100027B'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.
PubMed 9777998
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Almitrine and Severe COVID-19 Patients in ICU [Almitrine et Patients COVID-19 en Reanimation (French)]
- ClinicalTrials.gov ID
- NCT04380727
- Acronym / sponsor ID
- 2020PI080_2
- Conditions
- COVID-19, Hypoxic Respiratory Failure
- Keywords
- Hypoxic pulmonary vasoconstriction, Prone position, intra-pulmonary shunt, SARS-CoV-2
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Central Hospital, Nancy, FranceUniversity, hospital or other
- Study start
- 20 Mar 2020 (actual)
- Primary completion
- 14 Apr 2020 (actual)
- Study completion
- 25 Apr 2020 (actual)
- First posted
- 8 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Target follow-up
- 2 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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).
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (3 listed)
- the presence of an acute cor-pulmonale on the trans-thoracic 2D Echo-Doppler
- abnormal liver function tests
- hyperlactatemia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
2 secondary outcomes
Changes from baseline PaO2 (mmHg)
Time frame: 8 hours
Changes from baseline ScvO2 (%)
Time frame: 8 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2020.
- Background: PubMed 32007143Chen 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.
- Background: PubMed 32171076Zhou 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.
- Background: PubMed 32228035Gattinoni 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.
- Background: PubMed 8100027Payen 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.
- Background: PubMed 9777998B'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.
- Individual participant dataSharing planned: Undecided. Collaborative register on COVID-19 having benn treated with almitrine
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marie Reine LOSSER, MD, PhD principal investigator
Central Hospital, Nancy, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COVID-19 and Hypoxic Respiratory Failure, run by Central Hospital, Nancy, France at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes from baseline PaO2 (mmHg) (time frame: 45 minutes after almitrine infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04380727, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2020.