Community-acquired PneumoniaCAP-NEXTNCT03360851
DiagNostic Study of Low-dose CT and multipleX PCR on Antibiotic Treatment and Outcome of Community-Acquired Pneumonia
A study testing low-dose CT and PoC-PCR in people with Community-acquired Pneumonia, run by MJM Bonten at 7 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Community-acquired Pneumonia
- What is being tested?
- low-dose CT and PoC-PCR
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,555 participants
- Where
- 7 sitesNetherlands
- Study dates
- 27 Nov 2017to 1 Mar 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Netherlands7 sites
Noordwest Ziekenhuisgroep
Alkmaar
Amphia Ziekenhuis
Breda
Catharina Ziekenhuis
Eindhoven
Ter Gooi Ziekenhuis
Hilversum
University Medical Center
Utrecht
Maxima MC
Veldhoven
Langeland Ziekenhuis
Zoetermeer
About this study
Official title: DiagNostic Intervention Study of Low-dose CT and multipleX PCR on Antibiotic Treatment and Outcome of Community-Acquired Pneumonia
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.
Read more
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
- Being tested
- low-dose CT, PoC-PCR
- Keywords
- Pneumonia, low-dose CT, low-dose computed tomography, point of care testing, multiplex PCR, lower respiratory tract infection, antibiotic stewardship
- Medical subject headings
- Community-Acquired Pneumonia, Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
low-dose CTDiagnostic test
see arm/group description
PoC-PCRDiagnostic test
see arm/group description
| Study group | Role | What they receive |
|---|---|---|
| Low-dose CT | Experimental | 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. Receives: Diagnostic Test: low-dose CT |
| PoC-PCR | Experimental | 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. Receives: Diagnostic Test: PoC-PCR |
| Standard care | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Days of therapy of broad-spectrum antibiotics
Days of treatment with broad-spectrum antibiotics during index admission. This will include antibiotic prescriptions provided at discharge.
Measured: throughout hospitalization, an average of 7 days
All-cause mortality
All-cause mortality within 90 days of admission.
Measured: 90 days
Secondary outcomes (8)
days of therapy with any antibiotic
Number of days of treatment with any antibiotics during index admission, including antibiotic prescriptions provided at discharge.
Measured: throughout hospitalization, an average of 7 days
all-cause mortality
Measured: 30 days
length of hospital stay
Measured: throughout hospitalization, an average of 7 days
adverse outcomes
Composite endpoint comprising ICU admission, in-hospital mortality, and readmission
Measured: 90 days
time to results
Time from admission to availability of the low-dose CT / PoC-PCR results.
Measured: throughout hospitalization, an average of 7 days
time to treatment recommendations
Time from admission to provision of a treatment recommendation following the low-dose CT / PoC-PCR results.
Measured: throughout hospitalization, an average of 7 days
change in antibiotic consumption
Whether changes were made in the antibiotic class during treatment
Measured: throughout hospitalization, an average of 7 days
time to change in antibiotic consumption
When changes were made in the antibiotic class during treatment
Measured: throughout hospitalization, an average of 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2017
- Study start27 Nov 2017
- Primary completion24 Jun 2020
- Study completion1 Mar 2021
Why it stopped: COVID-19 pandemic has changed routine diagnostic workup of patients admitted with pneumonia. Continuation of the trial was felt to invalidate the study results.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Community-acquired PneumoniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel cluster-randomised trial with historical control period
- Masking
- None (open label)
- Enrolment
- 3,555 participants (actual)
Sponsor and investigators
- Lead sponsor
- MJM Bonten
- Sponsor type
- University, hospital or other
- Collaborators
- BioMérieux
- Responsible party
- Sponsor-investigator, MJM Bonten, UMC Utrecht
- Investigators
- Marc JM Bonten, MD, PhD, Principal investigator, University Medical Center Utrecht, the Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03360851
- Sponsor's protocol ID
- NL61857.041.17
- Acronym
- CAP-NEXT
- Status last verified
- May 2021
- First submitted
- 27 Oct 2017
- Last updated
- 21 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Publications
Zhang L, Aleva RM, Ammerlaan HSM, Ayuketah-Ekokobe FA, Boersma WG, Kluytmans JAJW, van der Linden P, Oosterheert JJ, de Jong PA, Bonten MJM, van Werkhoven CH; CAP-NEXT Study Group. Impact of low-dose chest computed tomography and multiplex PCR on antibiotic usage for community-acquired pneumonia: multicentre prospective controlled before-after study with cluster randomization. Clin Microbiol Infect. 2026 Jul 1:S1198-743X(26)00340-X. doi: 10.1016/j.cmi.2026.06.027. Online ahead of print.
PubMed 42385823
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DiagNostic Intervention Study of Low-dose CT and multipleX PCR on Antibiotic Treatment and Outcome of Community-Acquired Pneumonia
- ClinicalTrials.gov ID
- NCT03360851
- Acronym / sponsor ID
- CAP-NEXT / NL61857.041.17
- 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
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: COVID-19 pandemic has changed routine diagnostic workup of patients admitted with pneumonia. Continuation of the trial was felt to invalidate the study results.
- Enrolment
- 3,555 participants (actual)
- Lead sponsor
- MJM BontenUniversity, hospital or other
- Collaborators
- BioMérieux
- Study start
- 27 Nov 2017 (actual)
- Primary completion
- 24 Jun 2020 (actual)
- Study completion
- 1 Mar 2021 (actual)
- First posted
- 4 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Parallel cluster-randomised trial with historical control period
| Arm | Type | Receives |
|---|---|---|
| Low-dose CT | Experimental | Diagnostic Test: low-dose CTA 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. |
| PoC-PCR | Experimental | Diagnostic Test: PoC-PCRThe 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. |
| Standard care | No intervention | –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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| low-dose CTsee arm/group description | Diagnostic test | Low-dose CT |
| PoC-PCRsee arm/group description | Diagnostic test | PoC-PCR |
Primary outcome
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.
8 secondary outcomes
days of therapy with any antibiotic
Time frame: throughout hospitalization, an average of 7 days
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
time to results
Time frame: throughout hospitalization, an average of 7 days
time to treatment recommendations
Time frame: throughout hospitalization, an average of 7 days
change in antibiotic consumption
Time frame: throughout hospitalization, an average of 7 days
time to change in antibiotic consumption
Time frame: throughout hospitalization, an average of 7 days
Results and safety
The study was stopped early (reason given: COVID-19 pandemic has changed routine diagnostic workup of patients admitted with pneumonia. Continuation of the trial was felt to invalidate the study results.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2021.
- Derived from this study: PubMed 42385823Zhang L, Aleva RM, Ammerlaan HSM, Ayuketah-Ekokobe FA, Boersma WG, Kluytmans JAJW, van der Linden P, Oosterheert JJ, de Jong PA, Bonten MJM, van Werkhoven CH; CAP-NEXT Study Group. Impact of low-dose chest computed tomography and multiplex PCR on antibiotic usage for community-acquired pneumonia: multicentre prospective controlled before-after study with cluster randomization. Clin Microbiol Infect. 2026 Jul 1:S1198-743X(26)00340-X. doi: 10.1016/j.cmi.2026.06.027. Online ahead of print.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc JM Bonten, MD, PhD principal investigator
University Medical Center Utrecht, the Netherlands
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing low-dose CT and PoC-PCR in people with Community-acquired Pneumonia, run by MJM Bonten at 7 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: COVID-19 pandemic has changed routine diagnostic workup of patients admitted with pneumonia. Continuation of the trial was felt to invalidate the study results.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Days of therapy of broad-spectrum antibiotics (time frame: throughout hospitalization, an average of 7 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03360851, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2021.