Determinants of COVID-19 Pneumonia (MC-19) (MC-19)

June 17, 2020 updated by: Geltrude Mingrone, Catholic University of the Sacred Heart

Major Determinants of COVID-19 Associated Pneumonia

Molecular testing (e.g PCR) of respiratory tract samples is the recommended method for the identification and laboratory confirmation of COVID-19 cases.

Recent evidence reported that the diagnostic accuracy of many of the available RT-PCR tests for detecting SARS-CoV2 may be lower than optimal.

Of course, the economical and clinical implications of diagnostic errors are of foremost significance and in case of infectious outbreaks, namely pandemics, the repercussions are amplified. False positives and false-negative results may jeopardize the health of a single patient and may affect the efficacy of containment of the outbreak and of public health policies.

In particular, false-negative results contribute to the ongoing of the infection causing further spread of the virus within the community, masking also other potentially infected people.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

As demonstrated by a study conducted by Ai et al., including 1014 suspect COVID-19 cases who underwent multiple RT-PCR testing and chest-CT, overall 88% of patients had positive CT scans while RT-PCR positivity was found only in 59% of all cases. Also, as reported by Yang et al, the total positive rate of RT-PCR for throat swab samples was reported to be about 30% to 60% at initial presentation. Thus, a negative result does not exclude the possibility of infection and should not be used as the only criterion for treatment of patient and management decisions.

Reasons for false negative RT-PCR may include the lack of identification or inadequate procedures for specimen collection, handling and storage, as well as active viral recombination or testing carried out of the diagnostic window.

From preliminary studies has emerged that patients may show very early but significant CT changes even before RT-PCR studies. Hence, the necessity for developing a combined approach for the diagnosis of these particular patients who present with negative RT-PCR test results.

The investigators hypotheses is that several patients who presented with pneumonia confirmed at CT scan during the Coronavirus outbreak, and who tested negative for SARS-CoV2 at RT-PCR could probably be affected by the disease and need to be carefully observed.

Primary end-point The primary end-point of our prospective, observational study is to assess if inpatients who presented with pneumonia but had a negative test for Covid-19 are positive at the serology for SARS-CoV-2.

Secondary end-points Among the other secondary end-points, the investigators aim is to find if the combination of CT scan and serology could help in the identification of those patients who were initially negative at laboratory testing alone.

Other secondary end-points are the efficacy of different pharmaceutical treatments against Covid-19 that were empirically started in those highly suspicious cases and the development of an approach useful for those patients who initially tested negative for Covid-19 infection.

Methods Before starting the study, the protocol will be submitted to and approved by the local Ethical Committees at the Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University, Rome, Italy. Before enrollment each subject will sign the informed consent.

Inclusion criteria: hospitalized subjects of both sexes aged 18 years or older with diagnosis of pneumonia, confirmed by chest imaging and oxygen saturation (SaO2) ≤ 94% in ambient air, Covid-19 test negative, given informed consent to data collection from the patient or from the patient's legal representative if the patient is too unwell to provide consent.

Exclusion criteria: age lower than 18 years, pregnancy or breast-feeding. Nasopharyngeal swab samples will be taken for quantitative real-time polymerase chain reaction to make diagnosis of Covid19 (2 repeated tests).

Data collected include time of symptoms (cough, fever, dyspnea, conjunctivitis, diarrhea, asthenia, arthralgia) age, sex, height, weight, education, alcohol and smoking habits, morbidities, plasma glucose, creatinine, transaminases, γ-GT, total cholesterol, HDL-cholesterol, triglycerides, complete blood count, D-dimer, lactic acid dehydrogenase (LDH), high-sensitivity C-reactive protein (hs-CRP), creatinkinase (CK), ferritin, HbA1c, chest X rays, chest CT scan, cultures, therapy for pneumonia, other treatments including anti-hypertensive and anti-hyperglycemic agents, body temperature, blood pressure, and oxygen flow rate or other types of oxygen treatment.

Five ml of plasma divided in aliquots of 1 ml each will be also obtained and stored at -80°C in anonymized way for future analysis, including third parties.

Sample size If there is truly no difference between the standard and experimental treatment (16% in both groups), then 260 patients are required to be 90% sure that the limits of a two-sided 90% confidence interval will exclude a difference between the standard and experimental group of more than 15% Significance (α) = 0.05 Power (1-β)= 90% Percentage deaths in both control and experimental group = 16% Equivalence limit = 15%

Calculation based on the formula:

n = 2 × f(α, β/2) × π × (100 - π) / d2 where π is the true percent 'success' in both the control and experimental treatment groups, and f(α, β) = [Φ-1(α) + Φ-1(β)]2 Φ-1 is the cumulative distribution function of a standardised normal deviate.

Statistics The association between recovery and patient groups will be tested by means of a Fisher exact test. A Cox Proportional-Hazard regression will be used to compare survival curves (times to improvement) among the studied groups by correcting for the administered therapy and for all the quantitative collected variables. Quantitative variables, measured at hospital admission, will be compared among groups using ANOVA. In univariable analyses, categorical variables, as gender, education, alcohol consumption and smoke habits will be analysed by means of a Chi-Squared test to study their association with the recovery, while a logistic regression model will be used to test possible quantitative predictors of recovery. A multivariable logistic model, with a stepwise selection procedure, will be then used to test all the variables that are significant in a univariable analysis.

Study Type

Observational

Enrollment (Actual)

520

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Roma, Italy, 00168
        • Fondazione Policlinico Universitario A. Gemelli IRCCS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Subjects hospitalized for pneumonia who tested negative at RT-PCR

Description

Inclusion Criteria:

  • diagnosis of pneumonia; Covid-19 test negative; hospitalized subjects; both sexes; given informed consent

Exclusion Criteria:

  • age lower than 18 years; pregnancy; breast-feeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Negative PCR Covid associated Pneumonia
Patients with pneumonia who test negative to RT-PCR
Diagnostic test: Serology for Covid-19
Antibody tests designed to provide results to individuals or healthcare providers can show whether someone was previously infected with SARS-CoV-2 being the RT-PCR negative for the population of patients
Positive PCR Covid associated Pneumonia
Patients with pneumonia from Covid 19

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serology
Time Frame: 3 weeks
assess if inpatients who presented with pneumonia but had a negative test for Covid-19 are positive at the serology for SARS-CoV-2.
3 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of CT scan and Serology
Time Frame: 3 weeks
to find if the combination of CT scan and serology could help us in the identification of those patients who were initially negative at laboratory testing alone.
3 weeks
Efficacy of different pharmaceutical treatments
Time Frame: 3 weeks
the efficacy of different pharmaceutical treatments against Covid-19
3 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Catholic University of the Sacred Heart

Investigators

  • Principal Investigator: Geltrude Mingrone, MD, Fondazione Policlinico Universitario A. Gemelli, IRCCS

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 13, 2020

Primary Completion (ACTUAL)

June 12, 2020

Study Completion (ACTUAL)

June 17, 2020

Study Registration Dates

First Submitted

May 13, 2020

First Submitted That Met QC Criteria

May 13, 2020

First Posted (ACTUAL)

May 14, 2020

Study Record Updates

Last Update Posted (ACTUAL)

June 19, 2020

Last Update Submitted That Met QC Criteria

June 17, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20200505

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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