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Effects in Oxygenation and Hypoxic Pulmonary Vasoconstriction in ARDS Secondary to SARS-CoV2 (COVID-19)

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ClinicalTrials.gov Identifier: NCT04998253
Recruitment Status : Completed
First Posted : August 10, 2021
Last Update Posted : August 13, 2021
Sponsor:
Information provided by (Responsible Party):
Adrian Palacios-Chavarria, MD, Unidad Temporal COVID-19 en Centro Citibanamex

Brief Summary:

Summary Currently, the COVID-19 pandemic has overtaken health systems worldwide, exceeding the capacity of intensive care units. In addition to this, countries such as the United States have reported a decrease in the supplies of drugs such as Propofol and Midazolam (traditionally used as sedatives in patients with invasive mechanical ventilation), so in the absence until now of a specific treatment against SARS-COV-2 virus, improving the support strategies in patients in the severe spectrum of the disease Acute Respiratory Distress Syndrome (ARDS) is a priority.

Given the global state of emergency due to COVID-19, the use of sevoflurane has the potential to mitigate the shortages of sedative drugs, promote the recovery of patients with ARDS, and potentially reduce mortality.

A study will be conducted to evaluate the effect of sevoflurane as inhalation sedation in patients with ARDS secondary to SARS-COV2 compared to the standard. The primary objective of the study is to assess the difference in oxygenation, for which the calculation of the partial pressure of arterial oxygen to fractional inspired oxygen concentration ratio (PaO2 / FiO2) will be used at 24 and 48 hours. Also, the effect of the possible attenuation or inhibition of hypoxic pulmonary vasoconstriction will be evaluated by hemodynamic monitoring with a pulmonary artery catheter and transthoracic echocardiography and its possible effect on the right ventricle.

Outcome: we expect an improvement in oxygenation and consequently a reduction in the days of invasive mechanical ventilation, stay in the intensive care unit (ICU) and hospital. In addition to evaluating its possible anti-inflammatory effect and probably establishing a safe and effective alternative and possibly with greater benefits compared to standard intravenous sedation.


Condition or disease Intervention/treatment Phase
Hypoxic Pulmonary Vasoconstriction Hypoxemia Acute Respiratory Distress Syndrome SARS-CoV-2 Acute Respiratory Disease Drug: Effects in oxygenation and hypoxic pulmonary vasoconstriction Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Target Population: Patients with ARDS secondary to COVID-19 on invasive mechanical ventilation.

Accessible population: Patients with ARDS secondary to COVID-19 on invasive mechanical ventilation admitted to the Temporary COVID-19 Citibanamex Unit.

7.3 Randomization Simple randomization will be carried out using an envelope containing each sedative with 2 treatment groups. Taking into account 5% losses, by the formula: Sample adjusted to losses = n (1/1 - R) n = number of subjects without losses R = expected proportion of losses A person outside the study will place the indicated therapy inside identical opaque envelopes numbered 1 to 82 and then in a closed box. We will use the envelopes consecutively with the indicated therapy. Neither the researcher nor the people related to the study or the treatment will know the therapy that each patient will receive.

Masking: Single (Care Provider)
Masking Description: A person outside the research group will randomize the patients through the simple selection of the two drugs, once their admission to the intensive care unit is requested. We will not carry out the blinding of the researchers since the use of sevoflurane requires an external computer that cannot be replicated for the control group.
Primary Purpose: Treatment
Official Title: A Randomized Pilot Clinical Trial of the Effects in Oxygenation and Hypoxic Pulmonary Vasoconstriction of Sevoflurane in Patient's Whit ARDS Secondary to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2)
Actual Study Start Date : October 1, 2020
Actual Primary Completion Date : November 30, 2020
Actual Study Completion Date : May 15, 2021


Arm Intervention/treatment
Experimental: Group 1: Sevofruorane (Svofast)

Experimental group: will receive sedation with sevoflurane with an infusion rate to maintain MAC of 0.7 and fentanyl 1mcg /kg/hour.

Inhalation sedation The AnaConda device (Sedana Medical, Ireland) is placed between the endotracheal tube and the ventilator circuit. The anesthetic infusion line is attached to a syringe, from where the anesthetic (sevoflurane) will be delivered to said device. The sample line will be taken to the anesthetic gas analyzer whit the Carescape B450 multiparametric monitors (General Electric, Finland) for MAC control. The anesthetic gas outlet port will be attached to the absorbent material container.

Drug: Effects in oxygenation and hypoxic pulmonary vasoconstriction

Determination of the anti-inflammatory effect. The anti-inflammatory effect is assessed with serum measurement of interleukin 6 (IL-6), C-reactive protein (CRP), ferritin, DHL (lactic dehydrogenase), taken by venipuncture on admission, at 24 and 48 hours.

The following measurements will be performed: pulmonary artery systolic and diastolic pressure (PASP, PADP respectively), central venous pressure (CVP), pulmonary artery occlusion pressure (PAOP), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), right ventricular stroke work (RVSW) and left ventricular work (LVSW). Stroke volume (and cardiac output) will be computed using the thermodilution technique averaging three consecutive injections with 10 ml of 0.9% saline solution.

Other Names:
  • 3. Compare anti-inflammatory effect (determined by serum levels of IL-6, CRP, ferritin, DHL) of sevoflurane against propofol.
  • 1. Compare the effect on the pulmonary circulation of sevoflurane against Propofol.

Active Comparator: Group 2: Propofol (Diprivant)

Control group: will receive sedation with Propofol (Diprivant) at doses of 20-50mcg/kg/min and fentanyl (Fentanest) at doses of 1 to 2mcg/kg /hour.

For both groups, the doses will be titrated to maintain a RASS score between -3 to -4 in both groups.

Both groups will receive cisatracurium (Nimbex) as a continuous infusion of 3 to 5mcg / kg/min for 48 hours. We will maintain sedation for both groups with the same scheme for 48 hours, after which the drugs used for sedation will be modified at the discretion of the intensive care physicians.

Drug: Effects in oxygenation and hypoxic pulmonary vasoconstriction

Determination of the anti-inflammatory effect. The anti-inflammatory effect is assessed with serum measurement of interleukin 6 (IL-6), C-reactive protein (CRP), ferritin, DHL (lactic dehydrogenase), taken by venipuncture on admission, at 24 and 48 hours.

The following measurements will be performed: pulmonary artery systolic and diastolic pressure (PASP, PADP respectively), central venous pressure (CVP), pulmonary artery occlusion pressure (PAOP), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), right ventricular stroke work (RVSW) and left ventricular work (LVSW). Stroke volume (and cardiac output) will be computed using the thermodilution technique averaging three consecutive injections with 10 ml of 0.9% saline solution.

Other Names:
  • 3. Compare anti-inflammatory effect (determined by serum levels of IL-6, CRP, ferritin, DHL) of sevoflurane against propofol.
  • 1. Compare the effect on the pulmonary circulation of sevoflurane against Propofol.




Primary Outcome Measures :
  1. Evaluation of Oxygenation [ Time Frame: 24 and 48 hours ]
    The primary objective of the study is measure the difference in the oxygenation whit two different methods of sedation, inhaled (sevorane) and intravenous (propofol). The oxygenation will be measured whit PaO2 / FiO2 ratio will be used, taking peripheral arterial blood, with FiO2 at 100% one hour after the started of sedation corresponding to each group, again at 24 and 48 hours.

  2. The effect in the hypoxic pulmonary vasoconstriction whit two different type sedation. [ Time Frame: 24 and 48 hours ]

    The changes in pulmonary vascular tone and will be measured invasively through a pulmonary arterial catheter (Swan-Ganz) for which the following formula will be used:

    PVR=(MPAP-LAP)/CO Where PVR = pulmonary vascular resistance (dyn*s/cm), MPAP = mean pulmonary artery pressure (mm Hg), LAP = left atrial pressure or pulmonary wedge pressure (mm Hg) and CO = cardiac output (L/min). *79.92 is a constant to equal the units.



Secondary Outcome Measures :
  1. Determination of the anti-inflammatory effect. [ Time Frame: 24 and 48 hours ]
    The anti-inflammatory effect will be measured with serum levels of interleukin 6 (IL-6), C-reactive protein (CRP), ferritin, DHL (lactic dehydrogenase), taken by venipuncture on admission, at 24 and 48 hours.

  2. Measurement of dead space. [ Time Frame: 24 and 48 hours ]

    The physiological dead space expressed as a percentage will be calculated using the Bohr formula:

    DS=(PACO2-PEtCO2)/PACO2 Where DS = dead space, PaCO2 = partial pressure of arterial CO2 in mmHg, PEtCO2 = end tidal CO2 pressure in mmHg.




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Over 18 years
  2. Both genders
  3. Diagnosis of COVID-19 (SARS-COV2) with moderate to severe ARDS from the Berlin classification (PaO2 / FiO2: < 200).

Exclusion Criteria:

  1. Acute kidney failure.
  2. Severe liver failure
  3. Suspected or documented intracranial hypertension.
  4. Family history of malignant hyperthermia.
  5. History of malignant hyperthermia.
  6. Documented chronic lung disease.
  7. Documented chronic pulmonary hypertension
  8. Patients who do not sign informed consent.

Information from the National Library of Medicine

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): NCT04998253


Locations
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Mexico
Adrián Palacios Chavarria
Mexico City, Mexico, 11800
Sponsors and Collaborators
Unidad Temporal COVID-19 en Centro Citibanamex
Publications of Results:

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Responsible Party: Adrian Palacios-Chavarria, MD, Principal investigator, Unidad Temporal COVID-19 en Centro Citibanamex
ClinicalTrials.gov Identifier: NCT04998253    
Other Study ID Numbers: 09-CIE-011-20160627
First Posted: August 10, 2021    Key Record Dates
Last Update Posted: August 13, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Respiratory Distress Syndrome
Respiratory Distress Syndrome, Newborn
Acute Lung Injury
Respiration Disorders
Respiratory Tract Diseases
Syndrome
Hypoxia
Disease
Pathologic Processes
Lung Diseases
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury
Signs and Symptoms, Respiratory
Anti-Inflammatory Agents
Propofol
Sevoflurane
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Platelet Aggregation Inhibitors
Anesthetics, Inhalation