DiagNostic Study of Low-dose CT and multipleX PCR on Antibiotic Treatment and Outcome of Community-Acquired Pneumonia (CAP-NEXT)
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|ClinicalTrials.gov Identifier: NCT03360851|
Recruitment Status : Recruiting
First Posted : December 4, 2017
Last Update Posted : December 4, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Community-acquired Pneumonia||Diagnostic Test: low-dose CT Diagnostic Test: PoC-PCR||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||3760 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Parallel cluster-randomised trial with historical control period|
|Masking:||None (Open Label)|
|Official Title:||DiagNostic Intervention Study of Low-dose CT and multipleX PCR on Antibiotic Treatment and Outcome of Community-Acquired Pneumonia|
|Actual Study Start Date :||November 27, 2017|
|Estimated Primary Completion Date :||March 31, 2020|
|Estimated Study Completion Date :||March 31, 2020|
Experimental: 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.
Diagnostic Test: low-dose CT
see arm/group description
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.
Diagnostic Test: PoC-PCR
see arm/group description
No Intervention: 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.
- Days of therapy of broad-spectrum antibiotics [ Time Frame: throughout hospitalization, an average of 7 days ]Days of treatment with broad-spectrum antibiotics during index admission. This will include antibiotic prescriptions provided at discharge.
- All-cause mortality [ Time Frame: 90 days ]All-cause mortality within 90 days of admission.
- days of therapy with any antibiotic [ Time Frame: throughout hospitalization, an average of 7 days ]Number of days of treatment with any antibiotics during index admission, including antibiotic prescriptions provided at discharge.
- all-cause mortality [ Time Frame: 30 days ]
- length of hospital stay [ Time Frame: throughout hospitalization, an average of 7 days ]
- adverse outcomes [ Time Frame: 90 days ]Composite endpoint comprising ICU admission, in-hospital mortality, and readmission
- time to results [ Time Frame: throughout hospitalization, an average of 7 days ]Time from admission to availability of the low-dose CT / PoC-PCR results.
- time to treatment recommendations [ Time Frame: throughout hospitalization, an average of 7 days ]Time from admission to provision of a treatment recommendation following the low-dose CT / PoC-PCR results.
- change in antibiotic consumption [ Time Frame: throughout hospitalization, an average of 7 days ]Whether changes were made in the antibiotic class during treatment
- time to change in antibiotic consumption [ Time Frame: throughout hospitalization, an average of 7 days ]When changes were made in the antibiotic class during treatment
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): NCT03360851
|Contact: Lufang Zhang, MDemail@example.com|
|Contact: Cornelis H van Werkhoven, MD, PhDfirstname.lastname@example.org|
|Noordwest Ziekenhuisgroep||Not yet recruiting|
|Contact: Wim Boersma, MD, PhD|
|Amphia Ziekenhuis||Not yet recruiting|
|Contact: Jan Kluytmans, MD, PhD|
|Catharina Ziekenhuis||Not yet recruiting|
|Contact: Heidi Ammerlaan, MD, PhD|
|Ter Gooi Ziekenhuis||Not yet recruiting|
|Contact: Paul van der Linden, PharmD, PhD|
|University Medical Center||Recruiting|
|Contact: Lufang Zhang, MD|
|Maxima MC||Not yet recruiting|
|Contact: Dirk de Munck, MD, PhD|
|Langeland Ziekenhuis||Not yet recruiting|
|Contact: Florence Ekokobe, MD, PhD|
|Principal Investigator:||Marc JM Bonten, MD, PhD||University Medical Center Utrecht, the Netherlands|