Clinical trial NCT03322670: Description of Pneumococcal Pneumonia
Official title: Description of Pneumococcal Community-acquired Pneumonia in General Practice in France
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Community-acquired Pneumonia
Keywords: community-acquired pneumonia
family practice
streptococcus pneumoniae
Lead sponsor: CNGE Conseil
Sponsor class: OTHER
First posted: 2017-10-26
Enrollment: 412
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: In France, patients who visit a General Practitioner and who have clinical signs suggestive of CAP at clinic visits.

For the control cohort, healthy patient who visit a General Practitioner in the two weeks following the inclusion of a patient with CAP confirmed on the chest X-ray

Brief summary: Statement of the problem:

Overprescription of antibiotics raises important public health issues because of the emergence of multiresistant bacteria by selection pressure. The results of the observational prospective study entitled "CAPA" on the description of 886 suspected cases of acute community-acquired pneumonia (CAP) treated in general practices in France confirm that, whatever the etiologic hypothesis and the results of the chest X-ray, these patients routinely receive antibiotics. Therefore, it is important to be able to distinguish cases of pneumococcal CAP in which early antibiotic treatment is justified from those cases for which another strategy could be considered.

Primary objective:

To identify the clinical, biological and radiological characteristics of patients with pneumococcal CAP amongst all patients with CAP radiologically confirmed, in general practice in France.

Design :

Prospective cross-sectional descriptive study.

Inclusion criteria. Adults older than 18 showing clinical signs suggestive of CAP (at least one sign of infection and at least one pulmonary sign) and able to realize chest X ray within 6 hours after prescription.

Patient follow-up procedures. Patients will be treated by standard of care according to French recommendations. After observing clinical signs suggestive of CAP, the physician prescribes a chest X-ray. Then, protocol-specific examinations (blood sample, oropharyngeal sample for multiplex polymerase chain reaction (PCR), sputum sample testing (induced expectoration if possible), urinary sample) will be performed on all out patients. Patients will be contacted again on day 28 to increase diagnostic certainty. For patients with clinical signs of CAP and hospitalized, the investigator will ask their consent to retrieve the hospital report, on or before day 28 and to be contacted on day 90.

Detailed description: The aim of the study is to enroll approximately 2000 patients with CAP in total. Approximately 1000 X-ray positive patients and 1000 X-ray negative patients will be enrolled over 18 months.

Investigating GPs will identify patients with clinical signs suggestive of CAP at clinic visits.

A chest X-ray will be prescribed in accordance with local standard of care practices for patients that do not require immediate hospitalization. Chest X-ray must be completed within the 6 hours following its prescription.

For the 1000 patients (patient enrolment will be monitored centrally) with a positive chest X-ray, all procedures will be undertaken according to the protocol. Patients will attend the local medical analysis laboratory for biological sample collection (blood, sputum, oropharyngeal swab for the PCR, and urine). If a patient has taken antibiotics prior to the clinic visit at which CAP is suspected, will only have urine samples collected.

As a diagnostic confirmation of the chest X-ray assessments, for the 1000 patients for whom the local radiologist will have diagnosed a parenchymal opacity compatible with CAP, 200 patients will be randomly selected by the clinical research organization (CRO Paris Descartes Necker Cochin). A central independent thoracic radiologist expert will re-read their chest X-ray. In case of insufficient agreement, all chest X-rays will be re-read.

Patients will be asked to complete and return a self-assessment questionnaire at day 7 (D7) and at day 14 (D14) on the number of work days missed, if any, interruption of occupational activity, and the number of days of restricted everyday activities or recreational.

Patients will be contacted by telephone at day 28, and day 90 if they are hospitalized between day 0 and day 28.

For the 1000 patients (patient enrolment will be monitored centrally) with a negative chest X-ray, no medical analysis will be performed. Only clinical examination data will be recorded. Patients will be contacted by telephone at day 28.

For patients who will be directly hospitalized before the completion of the additional examinations, they will be contacted by telephone at day 28 to retrieve the hospitalization report and at day 90.

Control Patients will be included for the assessment of Pneumococcal urine antigen detection (UAD) Assay: in the two weeks following the inclusion of a patient with CAP, investigators should include a control patient according to the control patient inclusion / exclusion criteria. For these healthy patients, the number of inclusion is limited to 400.

Eligibility criteria: Inclusion Criteria:

- Inclusion criteria for suspected CAP population:

* Age ≥18 years
* Presence of at least 2 signs suggestive of CAP on presentation at general practice (one general sign of infection and one sign of pulmonary localization):

  * at least one sign of infection

    * fever \> 38.5°C (maximum temperature measured by the patient or GP)
    * tachycardia \> 100 /min
    * hyperpnea \> 20/min
    * global impression of severity\*
    * muscle aches, fatigue, or chills
  * and at least one sign of pulmonary localization

    * cough
    * unilateral chest pain
    * purulent or non-purulent sputum
    * auscultatory abnormality compatible with CAP (focus of crackles)
* Affiliation with health insurance system
* Chest X-ray performed within 6 hours of presenting to the general practice
* Willing and capable of providing blood, oropharyngeal urine samples, and sputum sample, for filling self-administered questionnaires to D7 and D14 and to be contacted again on D28 and on D90 if necessary, if chest X-ray is positive.
* Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.

  * Inclusion criteria for who do not wish to participate in the full study or who have not received a chest X-ray
* Age ≥18 years
* Presence of at least 2 signs suggestive of CAP on presentation at general practice (one general sign of infection and one sign of pulmonary localization):

  * at least one sign of infection

    * fever \> 38.5°C (maximum temperature measured by the patient or GP)
    * tachycardia \> 100 /min
    * hyperpnea \> 20/min
    * global impression of severity\*
    * muscle aches, fatigue, or chills
  * and at least one sign of pulmonary localization

    * cough
    * unilateral chest pain
    * purulent or non-purulent sputum
    * auscultatory abnormality compatible with CAP (focus of crackles)
    * Control Inclusion Criteria

Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study:

* A signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
* Age ≥18 years.
* Patients who are will to provide a urine sample

Exclusion Criteria:

* Exclusion criteria for suspected CAP population:

  * conditions of medical treatment not allowing for chest X-ray within 6 hours after diagnosis of CAP
  * contraindication to chest X-ray
  * conditions of medical management not allowing the realization of biological and bacteriological examinations within 8 hours of D0 consultation (except for patient immediately hospitalized)
  * chest X-ray finding not compatible with CAP : chest X-ray showing another lung disease than a CAP (for example: pulmonary neoplasia, tuberculosis, pulmonary embolism)
* Control Exclusion Criteria

Patients presenting with any of the following will not be included in the study:

* Patients who are investigational site staff members or relatives of those site staff member or subjects who are Pfizer employees directly involved in the conduct of the trial.
* Patients with suspicion of CAP or other respiratory infectious diseases, as well as evidence of or documented concomitant infectious disease.
* Patients residing in any long-term care facilities (for example, nursing homes, respite care facilities, etc).
* Patients with known bronchial obstruction or a history of post-obstructive pneumonia. Chronic obstructive pulmonary disease (COPD) is permissible, provided there has not been an exacerbation within the 3 months prior to enrollment.
* Patients with primary lung cancer or another malignancy metastatic to the lungs.
* Patients with fever (measured temperature of ≥38.0° C measured by a healthcare provider).
* Patients with significant immunosuppressive disease such as AIDS, leukemia, etc.
* Patients with either pneumococcal conjugate vaccine (PCV) and/or pneumococcal polysaccharide vaccine (PPV) administration within the past 30 days.

Primary outcomes:
measure: Percentage of pneumococcal CAP amongst the other etiological CAP with a positive chest X-ray
timeFrame: Day 0
Secondary outcomes:
measure: Description of clinical characteristics of patients treated in general practice for a radiologically confirmed CAP, based on the microbiological etiologies
timeFrame: Day 0
Other outcomes:
measure: Description of biological characteristics of patients treated in general practice for a radiologically confirmed CAP, based on the microbiological etiologies
timeFrame: Day 0
measure: Description radiological characteristics of patients treated in general practice for a radiologically confirmed CAP, based on all the microbiological etiologies.
timeFrame: day 0
measure: Incidence rate of pneumococcal CAP radiologically confirmed on chest X-ray, in the general practitioners settings
timeFrame: Day 0
measure: Descriptive analysis of Streptococcus pneumoniae serotypes identified on the urine assays.
timeFrame: Day 0
measure: Descriptive analysis of Streptococcus pneumoniae serotypes identified on the blood culture
timeFrame: Day 0
measure: Descriptive analysis of Streptococcus pneumoniae serotypes identified on the sputum culture
timeFrame: Day 0
measure: Assessment of costs generated by pneumococcal CAP managed in ambulatory setting.
timeFrame: Day 90
Locations:
city: Paris
country: France
facility: URC-CIC Paris Descartes-Cochin-Necker
Study officials:
affiliation: University Paris Descartes
name: Serge Gilberg, Professor
role: PRINCIPAL_INVESTIGATOR
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