International Lung UltraSound Analysis (ILUSA) Study

Sponsor

KU Leuven (Other)

Overall Status

Unknown status

CT.gov ID

NCT04353141

Collaborator

(none)

1,850

Enrollment

Locations

8.1

Anticipated Duration (Months)

264.3

Patients Per Site

32.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Currently there is a great need for an accurately and rapid assessment of patients suspected for Covid-19. Like CT, Lung Ultrasound (LUS) examination can potentially help with the initial triage of patients but also help track the evolution of the disease. LUS can be used in every setting, including settings with limited infrastructure, allowing the reduction of disparities in trials participation. LUS is also a practical approach that can be used by obstetricians/gynecologists, who are the primary care givers in the labour and delivery room.

The International Lung UltraSound Analysis (ILUSA) Study is an international multicenter prospective explorative observational study to assess the predictive value of LUS in Covid-19 suspected and diagnosed pregnant patients.

Condition or Disease	Intervention/Treatment	Phase
COVID Pregnancy Complications, Infectious Pregnancy Related Pregnancy, High Risk Pregnancy Disease Pneumonia Pneumonia, Viral Diagnoses Disease	Diagnostic Test: standardized Lung Ultrasound (LUS) examination

Detailed Description

During the current COVID-19 outbreak, all patient groups have been affected, also the most fragile such as the pregnant women. Although experts provided general suggestions on the best management of pregnant women with suspected or confirmed COVID-19, these considerations are mainly based on retrospective studies or case series. No prospective study is currently available about management of confirmed or suspected patients during pregnancy. Moreover, only limited outcome data is available on the management of asymptomatic SARS-CoV-2 positive pregnant patients, many of whom subsequently develop disease symptoms.

The current gold standard for the etiological diagnosis of COVID-19 infection is analysis of respiratory tract specimens by (real-time) reverse transcription polymerase chain reaction (RT-PCR). However, this test has a high false-negative rate, due to both nasopharyngeal swab sampling error, which often requires repeat sampling, and changing viral burden. Currently, high-resolution computed tomography (CT) is the main tool for primary diagnosis and evaluation of disease severity in patients affected by COVID-19 infection. Chest CT scan also demonstrated a specificity even superior to the nasal/pharyngeal swab for diagnosis. Yet, radiation exposure should ideally be avoided at all times in pregnancy. A radiation-free point-of-care diagnostic tool, such as lung ultrasound (LUS) examination, would be particularly useful for assessing the lungs of pregnant women. Indeed, LUS examination has recently been suggested by the Chinese Critical Care Ultrasound Study Group and the Italian Academy of Thoracic Ultrasound as an accurate tool to detect lung involvement during COVID-19.

In pregnant patients, LUS could be a valid alternative imaging tool to thoracic CT to guarantee appropriate care for these patients. Symptomatic patients with a low risk of developing serious disease may be possibly reassured, and could leave the hospital soon after delivery. On the other hand LUS could possibly indicate patients at higher risk for future need of oxygen or ventilation support, and who might need more careful monitoring and longer hospitalization. In view of the wide availability in delivery suites, the low cost and easy bedside application LUS could also be readily repeated during patient follow up as needed. LUS has been traditionally employed by non-radiologists as an adjunctive clinical instrument. Obstetricians represent a category of clinicians who use ultrasound in their daily routine practice. From a technical point of view, examination of the lungs at the time of obstetric ultrasound evaluation could be feasible for obstetricians and gynaecologists.

Currently there is a great need for an accurately and rapid assessment of patients suspected for Covid-19. Like CT, LUS can potentially help with the initial triage of patients but also help track the evolution of the disease. LUS can be used in every setting, including settings with limited infrastructure, allowing the reduction of disparities in trials participation. LUS is also a practical approach that can be used by obstetricians/gynecologists, who are the primary care givers in the labour and delivery room.

Study Design

Study Type:

Observational

Anticipated Enrollment :

1850 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

A Prospective International Lung UltraSound Analysis (ILUSA) Study in Tertiary Maternity Wards During the SARS-CoV-2 Pandemic

Actual Study Start Date :

Apr 28, 2020

Anticipated Primary Completion Date :

May 31, 2020

Anticipated Study Completion Date :

Dec 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Pregnant patients with confirmed COVID-19 infection	Diagnostic Test: standardized Lung Ultrasound (LUS) examination 14 areas (three posterior, two lateral and two anterior) will be assigned a COVID-LUS score: Score 0 (Normal pattern), Score 1 (Pattern of mild disease), Score 2 (Pattern of moderate disease), Score 3 (Pattern of severe disease). Classification of LUS result: LUS NEGATIVE: Group A = Score 0 in all 14 areas OR score =1 in areas of one site (right or left). It means that score 1 is pathological only when present bilaterally; LUS POSITIVE: both group B and C have to be considered positive: Group B (MILD DISEASE) = Score 1 in at least two areas localized bilaterally and no areas with score >1; Group C (MODERATE/SEVERE DISEASE)= Score >2 in at least two areas localized bilaterally
Pregnant patients symptomatic for COVID-19 Symptomatic patients suspicious for COVID-19 infection (swab is taken on admission)	Diagnostic Test: standardized Lung Ultrasound (LUS) examination 14 areas (three posterior, two lateral and two anterior) will be assigned a COVID-LUS score: Score 0 (Normal pattern), Score 1 (Pattern of mild disease), Score 2 (Pattern of moderate disease), Score 3 (Pattern of severe disease). Classification of LUS result: LUS NEGATIVE: Group A = Score 0 in all 14 areas OR score =1 in areas of one site (right or left). It means that score 1 is pathological only when present bilaterally; LUS POSITIVE: both group B and C have to be considered positive: Group B (MILD DISEASE) = Score 1 in at least two areas localized bilaterally and no areas with score >1; Group C (MODERATE/SEVERE DISEASE)= Score >2 in at least two areas localized bilaterally
Pregnant patients asymptomatic for COVID19 Patients asymptomatic for COVID19 with other feto-maternal diseases or who come for delivery or caesarean section	Diagnostic Test: standardized Lung Ultrasound (LUS) examination 14 areas (three posterior, two lateral and two anterior) will be assigned a COVID-LUS score: Score 0 (Normal pattern), Score 1 (Pattern of mild disease), Score 2 (Pattern of moderate disease), Score 3 (Pattern of severe disease). Classification of LUS result: LUS NEGATIVE: Group A = Score 0 in all 14 areas OR score =1 in areas of one site (right or left). It means that score 1 is pathological only when present bilaterally; LUS POSITIVE: both group B and C have to be considered positive: Group B (MILD DISEASE) = Score 1 in at least two areas localized bilaterally and no areas with score >1; Group C (MODERATE/SEVERE DISEASE)= Score >2 in at least two areas localized bilaterally

Arm

Intervention/Treatment

Pregnant patients with confirmed COVID-19 infection

Diagnostic Test: standardized Lung Ultrasound (LUS) examination

14 areas (three posterior, two lateral and two anterior) will be assigned a COVID-LUS score: Score 0 (Normal pattern), Score 1 (Pattern of mild disease), Score 2 (Pattern of moderate disease), Score 3 (Pattern of severe disease). Classification of LUS result: LUS NEGATIVE: Group A = Score 0 in all 14 areas OR score =1 in areas of one site (right or left). It means that score 1 is pathological only when present bilaterally; LUS POSITIVE: both group B and C have to be considered positive: Group B (MILD DISEASE) = Score 1 in at least two areas localized bilaterally and no areas with score >1; Group C (MODERATE/SEVERE DISEASE)= Score >2 in at least two areas localized bilaterally

Pregnant patients symptomatic for COVID-19

Symptomatic patients suspicious for COVID-19 infection (swab is taken on admission)

Diagnostic Test: standardized Lung Ultrasound (LUS) examination

Pregnant patients asymptomatic for COVID19

Patients asymptomatic for COVID19 with other feto-maternal diseases or who come for delivery or caesarean section

Diagnostic Test: standardized Lung Ultrasound (LUS) examination

Outcome Measures

Primary Outcome Measures

Diagnostic performance of LUS to predict poor outcome [outcome one week after enrollment into the study]
The primary endpoint is diagnostic performance in terms of the area under the receiver operating characteristic curve (AUC, also known as the c-statistic) and sensitivity and specificity with regard to the prediction of poor outcome. Outcome at one week from admission: good outcome includes discharge or inpatient breathing in free air; poor outcome includes patient with oxygen support, patients with CPAP/ high oxygen flow cannula, or patient with endotracheal intubation during the week.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants eligible for inclusion in this Trial must meet all of the following criteria:

Voluntary written informed consent of the participant or their legally authorized representative obtained prior to any screening procedures

Pregnant patients admitted to the Hospital during the COVID-19 pandemic:

Patients with confirmed COVID-19 infection (see below)
Symptomatic patients suspicious for COVID-19 infection (swab is taken on admission)
Patients asymptomatic for COVID19 with other feto-maternal diseases or who come for delivery or caesarean section

All participants that are considered for Trial participation, per the above criteria will be documented on the Screening Log, including Screen Failures.

Definition of suspected case (WHO guideline, ISUOG)

A patient with acute respiratory illness (fever and at least one sign/symptom of respiratory disease (e.g. cough, shortness of breath)) AND with no other etiology that fully explains the clinical presentation AND a history of travel to or residence in a country/area or territory reporting local transmission of COVID-19 infection during the 14 days prior to symptom onset; OR
A patient with any acute respiratory illness AND who has been in contact with a confirmed or probable case of COVID-19 infection in the 14 days prior to onset of symptoms; OR
A patient with severe acute respiratory infection (fever and at least one sign/symptom of respiratory disease (e.g. cough, shortness breath)) AND who requires hospitalization AND who has no other etiology that fully explains the clinical presentation.

Exclusion Criteria:

Participants eligible for this Trial must not meet any of the following criteria:

Maternal lung pre-existing disease
Maternal cardiac problems
Severely ill patients in unstable condition requiring immediate life-saving procedures

Participants who meet one or more of the above exclusion criteria must not proceed to be enrolled in the Trial and will be identified on the Screening Log as Screen Failure.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	University Hospitals Leuven	Leuven	Belgium	3000
2	University of Brescia	Brescia	Italy
3	University of Foggia	Foggia	Italy
4	University of Milan	Milan	Italy
5	University of Parma	Parma	Italy
6	Fondazione Policlinico Universitario A. Gemelli	Roma	Italy
7	Queen Charlotte's & Chelsea Hospital	London	United Kingdom

Sponsors and Collaborators

KU Leuven

Investigators

Study Chair: Dirk Timmerman, PhD, KU Leuven, Leuven BE
Study Chair: Antonia Testa, PhD, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome IT
Study Chair: Jan Deprest, PhD, KU Leuven
Study Chair: Francesca Moro, MD, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome IT
Study Chair: Tom Bourne, PhD, Queen Charlotte's & Chelsea Hospital, Imperial College London, London, UK
Study Chair: Giovanni Scambia, PhD, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome IT
Study Chair: Antonio Lanzone, PhD, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome IT