Clinical trial NCT03360851: DiagNostic Study of Low-dose CT and multipleX PCR on Antibiotic Treatment and Outcome of Community-Acquired Pneumonia
Official title: DiagNostic Intervention Study of Low-dose CT and multipleX PCR on Antibiotic Treatment and Outcome of Community-Acquired Pneumonia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Community-acquired Pneumonia
Keywords: Pneumonia
low-dose CT
low-dose computed tomography
point of care testing
multiplex PCR
lower respiratory tract infection
antibiotic stewardship
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: BioMérieux
First posted: 2017-12-04
Enrollment: 3555
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel cluster-randomised trial with historical control period
Primary purpose: DIAGNOSTIC

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.


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

Primary outcomes:
measure: Days of therapy of broad-spectrum antibiotics
timeFrame: throughout hospitalization, an average of 7 days
measure: All-cause mortality
timeFrame: 90 days
Secondary outcomes:
measure: days of therapy with any antibiotic
timeFrame: throughout hospitalization, an average of 7 days
measure: all-cause mortality
timeFrame: 30 days
measure: length of hospital stay
timeFrame: throughout hospitalization, an average of 7 days
measure: adverse outcomes
timeFrame: 90 days
measure: time to results
timeFrame: throughout hospitalization, an average of 7 days
measure: time to treatment recommendations
timeFrame: throughout hospitalization, an average of 7 days
measure: change in antibiotic consumption
timeFrame: throughout hospitalization, an average of 7 days
measure: time to change in antibiotic consumption
timeFrame: throughout hospitalization, an average of 7 days
Other outcomes:
Locations:
city: Alkmaar
country: Netherlands
facility: Noordwest Ziekenhuisgroep
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Hilversum
country: Netherlands
facility: Ter Gooi Ziekenhuis
city: Utrecht
country: Netherlands
facility: University Medical Center
city: Veldhoven
country: Netherlands
facility: Maxima MC
city: Zoetermeer
country: Netherlands
facility: Langeland Ziekenhuis
Study officials:
affiliation: University Medical Center Utrecht, the Netherlands
name: Marc JM Bonten, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: