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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
Sponsor:
Collaborator:
BioMérieux
Information provided by (Responsible Party):
MJM Bonten, UMC Utrecht

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.


Condition or disease Intervention/treatment Phase
Community-acquired Pneumonia Diagnostic Test: low-dose CT Diagnostic Test: PoC-PCR Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3760 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Parallel cluster-randomised trial with historical control period
Masking: None (Open Label)
Primary Purpose: Diagnostic
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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

Experimental: 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.
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.



Primary Outcome Measures :
  1. 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.

  2. All-cause mortality [ Time Frame: 90 days ]
    All-cause mortality within 90 days of admission.


Secondary Outcome Measures :
  1. 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.

  2. all-cause mortality [ Time Frame: 30 days ]
  3. length of hospital stay [ Time Frame: throughout hospitalization, an average of 7 days ]
  4. adverse outcomes [ Time Frame: 90 days ]
    Composite endpoint comprising ICU admission, in-hospital mortality, and readmission

  5. 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.

  6. 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.

  7. change in antibiotic consumption [ Time Frame: throughout hospitalization, an average of 7 days ]
    Whether changes were made in the antibiotic class during treatment

  8. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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


Contacts
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Contact: Lufang Zhang, MD 00317555555 l.zhang-3@umcutrecht.nl
Contact: Cornelis H van Werkhoven, MD, PhD c.h.vanwerkhoven@umcutrecht.nl

Locations
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Netherlands
Noordwest Ziekenhuisgroep Not yet recruiting
Alkmaar, Netherlands
Contact: Wim Boersma, MD, PhD         
Amphia Ziekenhuis Not yet recruiting
Breda, Netherlands
Contact: Jan Kluytmans, MD, PhD         
Catharina Ziekenhuis Not yet recruiting
Eindhoven, Netherlands
Contact: Heidi Ammerlaan, MD, PhD         
Ter Gooi Ziekenhuis Not yet recruiting
Hilversum, Netherlands
Contact: Paul van der Linden, PharmD, PhD         
University Medical Center Recruiting
Utrecht, Netherlands
Contact: Lufang Zhang, MD         
Maxima MC Not yet recruiting
Veldhoven, Netherlands
Contact: Dirk de Munck, MD, PhD         
Langeland Ziekenhuis Not yet recruiting
Zoetermeer, Netherlands
Contact: Florence Ekokobe, MD, PhD         
Sponsors and Collaborators
MJM Bonten
BioMérieux
Investigators
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Principal Investigator: Marc JM Bonten, MD, PhD University Medical Center Utrecht, the Netherlands

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Responsible Party: MJM Bonten, Professor of molecular epidemiology of infectious diseases, head of department of medical microbiology, UMC Utrecht
ClinicalTrials.gov Identifier: NCT03360851     History of Changes
Other Study ID Numbers: NL61857.041.17
First Posted: December 4, 2017    Key Record Dates
Last Update Posted: December 4, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Anti-Bacterial Agents
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents