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Lung Injury (Pulmonary Edema) in COVID-19: Treatment With Furosemide and Negative Fluid Balance (NEGBAL)

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ClinicalTrials.gov Identifier: NCT05304702
Recruitment Status : Completed
First Posted : March 31, 2022
Last Update Posted : April 22, 2022
Sponsor:
Information provided by (Responsible Party):
José Luis Francisco Santos, Clinica Colon

Brief Summary:

In COVID-19, pulmonary edema has been attributed to "cytokine storm". However, it is known that SARS-CoV-2 promotes angiotensin-converting enzyme 2 deficiency, it increases angiotensin II and this triggers volume overload. The current study is based on patients with COVID-19, tomographic evidence of pulmonary edema and volume overload. These patients received a standard goal-guided diuretic (furosemide) treatment: Negative Fluid Balance (NEGBAL) approach. This retrospective observational study consists of comparing two groups. The cases show patients with COVID-19 and lung injury treated with NEGBAL approach comparing it to the control group consisting of patients with COVID-19 and lung injury receiving standard treatment. Medical records of 120 critically ill patients (60 in NEGBAL group and 60 in control group) were reviewed: demographic, clinical, laboratory, blood gas and chest tomography (CT) before and during NEGBAL.

Once NEGBAL strategy started, different aspects were evaluated: clinical, gasometric and biochemical evolution until the 8th day, tomography until the 12th day, ICU stay, hospital stay and morbidity and mortality until the 30th day.


Condition or disease
COVID-19

Show Show detailed description

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Study Type : Observational
Actual Enrollment : 120 participants
Observational Model: Case-Control
Time Perspective: Retrospective
Official Title: Lung Injury (Pulmonary Edema) in COVID-19: Treatment With Furosemide and Negative Fluid Balance (NEGBAL): a Case-Control Study
Actual Study Start Date : November 28, 2021
Actual Primary Completion Date : March 31, 2022
Actual Study Completion Date : March 31, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Furosemide

Group/Cohort
NEGBAL

Negative Fluid Balance (NEGBAL) Approach:

COVID-19 patients with tomographic detection of pulmonary edema (dilated superior vena cava, large pulmonary arteries, diffuse interstitial infiltrates with Kerley lines, and dilated right ventricle or dilated cardiac axis) treated with NEGBAL approach. This consisted of oral hydric restriction and use of diuretics (20 mg of furosemide, intravenous bolus, followed by furosemide in endovenous continuous infusion, starting at 60 mg/day).

The objective of this approach was to achieve negative fluid balance, between 600 to 1400 mL/day adjusted to body surface area, with a final target of 8-10% of body weight in up to 8 days. The furosemide dose was titrated considering heart rate and blood pressure, target fluid balance, hematocrit, and serum creatinine.

NO-NEGBAL

Treatment for COVID-19 pneumonia in this series were based on standard recommendations.

All patients in this group received dexamethasone 6 mg/day and thromboembolic prevention with enoxaparin 40 mg/day.

Participants in the NO-NEGBAL group, did not received a NEGBAL approach as treatment.




Primary Outcome Measures :
  1. Mortality [ Time Frame: Until the 30th day after admission or discharge ]
    Mortality measured in days after admission

  2. Oxygenation [ Time Frame: From admission to day 7; until discharge, death, or until the 30th day, depending on which appears first. ]
    Evolution of oxygenation during hospitalization (measured by PaO2/FiO2). To analyze the correlation between the variation of the PaO2/FiO2 ratio and the NEGBAL variables, a linear regression model of the form PAFIBAL~β0+β1NEGBAL was used. For the model, the response variable PAFIBAL was registered as the difference in the PaO2/FiO2 between admission to NEGBAL to day 7. Continuous variables were expressed as means. Categorical variables were summarized as counts. No changes (adjustments) were made for missing data. The paired sample T test was used. All statistical tests were 2-tailed. A p-value < 0.05 was considered statistically significant. The analysis was not adjusted for multiple comparisons and given the possibility of a type I error, the findings should be interpreted as exploratory and descriptive. All analyses were performed using R software, version 4.1.1 (R Foundation for Statistical Computing)


Secondary Outcome Measures :
  1. Number of participants with mechanical ventilation requirements (MV invasive) [ Time Frame: Until discharge, death, or up to 30 days, depending on which appears first. ]
  2. CT infiltrates [ Time Frame: Prior to starting NEGBAL approach, between admission to day 4, day 8 and day 12 of NEGBAL. ]
    Evaluation of CT infiltrates, measured through the score described by Pan F et al, used as a semiquantitative measurement using the sum of lung involvement-5 lobes. Each lobe on a scale from 0 (normal) to 5 (maximum infiltrate) being the maximum CT score 25.

  3. Measurement of the superior vena cava diameter [ Time Frame: Prior to starting NEGBAL approach, between admission to day 4, day 8 and day 12 of NEGBAL. ]
    Measured in CT just above the arch of the azygos veins. Unit of measurement: millimeters (mm)

  4. Measurement of cardiac axis diameter [ Time Frame: Prior to starting NEGBAL approach, between admission to day 4, day 8 and day 12 of NEGBAL. ]
    Transverse measurement across the 4 cavities (in centimeters)


Other Outcome Measures:
  1. Length of stay in ICU [ Time Frame: Until discharge, death, or until the 30th day, depending on which appears first. ]
  2. Length of hospital stay [ Time Frame: Until discharge, death, or until the 30th day, depending on which appears first. ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Population of patients with COVID-19 admitted to the ICU in a high complexity healthcare institution of Mar del Plata, Argentina.
Criteria

Inclusion Criteria:

Inclusion criteria for patients subjected to NEGBAL group are as follows:

  • confirmed diagnosis of COVID-19
  • PaO2/FiO2 (ratio of arterial oxygen partial pressure to fractional inspired oxygen) <300;
  • Patients over 18 years of age and
  • tomographic evidence of acute pulmonary edema, defined as dilated superior vena cava, large pulmonary arteries, diffuse interstitial infiltrates with Kerley lines, and dilated right ventricle or dilated cardiac axis.

Patients subjected to NEGBAL underwent a treatment with furosemide in continuous intravenous infusion, guided by objectives: Negative Fluid Balance approach (NEGBAL).

Inclusion criteria for patients subjected to NO-NEGBAL-Control Group- are as follows:

  • confirmed diagnosis of COVID-19 through real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay with samples obtained from nasopharyngeal swab or positive antinucleocapsid immunoglobulin M (IgM) antibodies;
  • ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) <300;
  • age older than 18 years, and
  • tomographic evidence of acute pulmonary edema, defined as dilated superior vena cava, large pulmonary arteries, diffuse interstitial infiltrates with Kerley lines, and dilated right ventricle or dilated cardiac axis.

Patients subjected to NO-NEGBAL group, did not receive NEGBAL approach as treatment.

Exclusion Criteria for both groups are as follows:

  • patients with prior indication of diuretics for another reason,
  • renal failure,
  • cardiac failure (diagnosis by echocardiography),
  • hepatic failure,
  • hypernatremia or hyponatremia,
  • hypotension or shock.

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): NCT05304702


Locations
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Argentina
Clínica Colón
Mar del Plata, Buenos Aires, Argentina, 7600
Sponsors and Collaborators
Clinica Colon
Investigators
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Principal Investigator: José LF Santos, MD Clínica Colón - Mar del Plata - Argentina
Publications:

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Responsible Party: José Luis Francisco Santos, Chief of Intensive Care Unit, Clinica Colon
ClinicalTrials.gov Identifier: NCT05304702    
Other Study ID Numbers: UTI-ESI-002
First Posted: March 31, 2022    Key Record Dates
Last Update Posted: April 22, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by José Luis Francisco Santos, Clinica Colon:
furosemide
edema
volume overload
diuretic
NEGBAL - Negative Fluid Balance
COVID-19
Additional relevant MeSH terms:
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COVID-19
Lung Injury
Pulmonary Edema
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Thoracic Injuries
Wounds and Injuries