DiagNostic Study of Low-dose CT and multipleX PCR on Antibiotic Treatment and Outcome of Community-Acquired Pneumonia

NCT ID: NCT03360851

Last Updated: 2021-05-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 3555 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-27
• Study Completion Date: 2021-03-01

Brief Summary

Rationale:

Uncertainty in the clinical and etiological diagnosis of community-acquired pneumonia (CAP) often leads to incorrect treatment and unnecessary use of broad-spectrum antibiotics. Establishing the clinical diagnosis of CAP is hampered by the suboptimal sensitivity of chest radiograph to detect pulmonary infiltrates (~70%). Establishing the etiological diagnosis is also hampered, mainly because of the inevitable diagnostic delays and low sensitivity of routine microbiological tests. There are currently no recommendations for low-dose chest computed tomography (low-dose CT) or viral and bacterial point-of-care multiplex polymerase chain reaction (PoC-PCR) in the diagnostic work-up of CAP patients, because the data supporting such an approach are lacking.

Objective: The aim of this study is to determine the added value of low-dose CT and PoC-PCR in the diagnostic workup of patients with CAP hospitalised to non-intensive care unit (ICU) wards in minimizing selective antibiotic pressure while maintaining patient safety.

Study design: Cluster-randomised controlled trial with historical control period.

Study population: Adult patients (>=18 years old) with a clinical diagnosis of CAP requiring hospitalisation to a non-ICU ward.

Intervention: Intervention arm 1: availability of PoC-PCR during the ER visit; intervention arm 2: performing low-dose CT from the ER or at least within 24 hours; control arm: standard care.

Main study parameters/endpoints: The primary effectiveness outcome is days of therapy of broad-spectrum antibiotics. The primary safety outcome, on which the sample size is calculated, is 90-day all-cause mortality.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: There are no risks associated with performing the PoC-PCR and the radiation of the low-dose CT is of negligible risk. Nasopharyngeal swab collection causes a temporary unpleasant sensation. The low-dose CT can reveal unexpected findings which may require additional diagnostic procedures, for which the treating physician will use state-of-the-art guidelines. Treatment recommendations to de-escalate or stop antibiotic treatment may be beneficial for the individual patient by minimising exposure to antibiotics and improve targeted use of antibiotics. Final decisions are always made by the treating physician taking into account all clinical information.

Conditions

Community-acquired Pneumonia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Low-dose CT

A low-dose chest CT-scan will be performed either directly from the ER or from the medical ward as soon as possible but within 24 hours of admission. The CT will be performed with a radiation dose \<0.5 mSv for a 70kg patient, as a replacement or in addition to the chest radiograph. Pregnancy will be an exclusion criterion for CT because of unwanted radiation exposure. CT interpretation will be performed by a radiologist. Test results will be communicated to the treating physician. Recommendations based on the CT may be to discontinue antibiotics in case of a noninfectious diagnosis that explains the presented signs and symptoms and to start treatment for the alternative diagnosis if needed, or to re-evaluate the CAP diagnosis if no signs of lobar or bronchopneumonia are detected on the CT.

Group Type: EXPERIMENTAL

low-dose CT

Intervention Type: DIAGNOSTIC_TEST

see arm/group description

PoC-PCR

The FilmArray real-time multiplex PCR (Biofire; bioMérieux) is a Point-of-Care PCR with a panel of respiratory viruses (adenovirus, coronavirus, human metapneumovirus, human rhinovirus/enterovirus, influenza A and B, parainfluenza virus, and respiratory syncytial virus), and three atypical pathogens (Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Bordetella pertussis), which will be performed on nasopharyngeal swab samples. Test results will be made available to the treating physician immediately. The treatment recommendation could be adaptation of antibiotic treatment for a documented atypical pathogen, a recommendation to not start or discontinue antibiotics when a virus is the only detected pathogen, or a recommendation to discontinue coverage of atypical pathogens.

Group Type: EXPERIMENTAL

PoC-PCR

Intervention Type: DIAGNOSTIC_TEST

see arm/group description

Standard care

All hospitals will continue the antibiotic stewardship activities employed during the baseline period as part of standard care. A representative of the Antibiotics-team (Team consisting of clinical microbiologists, infectious diseases specialist and clinical pharmacists supervising in-hospital antibiotic use) will monitor the empirical antibiotic treatment of patients hospitalized with CAP to non-ICU wards and provide feedback if indicated.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

low-dose CT

see arm/group description

Intervention Type: DIAGNOSTIC_TEST

PoC-PCR

see arm/group description

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• aged 18 years or above;
• working diagnosis of CAP at the emergency department with the presence of at least two clinical criteria or one clinical criterion and radiological evidence of CAP, with no other explanation for the signs and symptoms;
• requiring hospitalisation to a non-ICU ward via the ER.

Exclusion Criteria

• Hospitalisation for two or more days in the last 14 days;
• Residence in a long-term care facility in the last 14 days;
• History of cystic fibrosis;
• Severe immunodeficiency

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioMérieux

INDUSTRY

Sponsor Role: collaborator

MJM Bonten

OTHER

Sponsor Role: lead

Responsible Party

MJM Bonten

Professor of molecular epidemiology of infectious diseases, head of department of medical microbiology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Marc JM Bonten, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Utrecht, the Netherlands

Locations

Noordwest Ziekenhuisgroep

Alkmaar, , Netherlands

Amphia Ziekenhuis

Breda, , Netherlands

Catharina Ziekenhuis

Eindhoven, , Netherlands

Ter Gooi Ziekenhuis

Hilversum, , Netherlands

University Medical Center

Utrecht, , Netherlands

Maxima MC

Veldhoven, , Netherlands

Langeland Ziekenhuis

Zoetermeer, , Netherlands

Countries

Netherlands

Other Identifiers

NL61857.041.17

Identifier Type: -

Identifier Source: org_study_id