Effects in Oxygenation and Hypoxic Pulmonary Vasoconstriction in ARDS Secondary to SARS-CoV2

NCT04998253 | Completed Early Phase 1 DMC

• 1 other identifier: 09-CIE-011-20160627
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypoxic Pulmonary Vasoconstriction; Hypoxemia; Acute Respiratory Distress Syndrome; SARS-CoV-2 Acute Respiratory Disease

Outcome Measures

Primary Outcomes (2)

• Evaluation of Oxygenation

  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.

  24 and 48 hours

• The effect in the hypoxic pulmonary vasoconstriction whit two different type sedation.

  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.

  24 and 48 hours

Secondary Outcomes (2)

• Determination of the anti-inflammatory effect.

  24 and 48 hours

• Measurement of dead space.

  24 and 48 hours

Study Arms (2)

Group 1: Sevofruorane (Svofast)

EXPERIMENTAL

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

Group 2: Propofol (Diprivant)

ACTIVE COMPARATOR

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

Interventions

Effects in oxygenation and hypoxic pulmonary vasoconstriction DRUG

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.

Also known as: 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.

Group 1: Sevofruorane (Svofast); Group 2: Propofol (Diprivant)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Acute kidney failure.
• Severe liver failure
• Suspected or documented intracranial hypertension.
• Family history of malignant hyperthermia.
• History of malignant hyperthermia.
• Documented chronic lung disease.
• Documented chronic pulmonary hypertension
• Patients who do not sign informed consent.

Sponsors & Collaborators

• Unidad Temporal COVID-19 en Centro Citibanamex: lead

Study Sites (1)

Adrián Palacios Chavarria

Mexico City, 11800, Mexico

Location

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MeSH Terms

Conditions

Hypoxia; Respiratory Distress Syndrome

Interventions

Treatment Outcome; Ferritins

Condition Hierarchy (Ancestors)

Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Prognosis; Diagnosis; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Health Care Evaluation Mechanisms; Health Care Quality, Access, and Evaluation; Iron-Binding Proteins; Carrier Proteins; Proteins; Amino Acids, Peptides, and Proteins; Metalloproteins

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: 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.

Study Record Dates

• First Submitted: May 19, 2021
• First Posted: August 10, 2021
• Study Start: October 1, 2020
• Primary Completion: November 30, 2020
• Study Completion: May 15, 2021
• Last Updated: August 13, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)