Clinical trial NCT03315403: Quantitative Polymerase Chain Reaction for Improved Detection of Pneumococci in CAP "CAPTAIN"
Official title: Community-Acquired Pneumonia: lytA TArgeted Real Time Quantitative Polymerase chaIN Reaction for Improved Detection of Pneumococci (CAPTAIN)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pneumonia, Pneumococcal
Community-acquired Pneumonia
Keywords: quantitative polymerase chain reaction
qPCR
autolysin
lytA
Pneumococcal pneumonia
Diagnostics
Community-acquired Pneumonia
Antibiotic resistance
Lead sponsor: Medical Center Alkmaar
Sponsor class: OTHER
First posted: 2017-10-20
Enrollment: 922
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patient group: Adult patients ≥18 years with diagnosis of CAP at the emergency department (ED).

Control groups (without CAP):

* Related controls (inclusion at ED)
* Unrelated healthy adults (inclusion at an outpatient preoperative appointment for any elective surgery)
* Stable COPD patients (inclusion at outpatient clinic for pulmonary diseases)
* COPD patients with an AECOPD (inclusion at ED)

Brief summary: The purpose of this study is to evaluate the added diagnostic value of a quantitative polymerase chain reaction targeting the lytA gene in detecting pneumococci in patients with community-acquired pneumonia.


Eligibility criteria: Inclusion Criteria:

Patients:

* Age 18 years or above;
* Presentation at the emergency department (ED);
* Working diagnosis of CAP at the ED with the presence of at least two of the following criteria:

  1. New or worsened coughing;
  2. Production of purulent sputum or change in sputum colour;
  3. Temperature \>38.0 ⁰C or ≤36.0 ⁰C (tympanic);
  4. Auscultatory findings consistent with pneumonia, including rales, evidence of pulmonary consolidation (dullness on percussion, bronchial breath sounds, rales, or egophony), or both;
  5. White blood cell count of \>10x10\^9 cells/L or \<4x10\^9 cells/L or \>15% bands;
  6. C-reactive protein level ≥30mg/L;
  7. Dyspnea, tachypnea, (\>20 breaths per minute), or hypoxemia (arterial pO2 \<60mmHg or peripheral O2 saturation \<90%).
* New consolidation(s) on the chest radiograph or computed tomography (CT);
* No other explanation for the signs and symptoms;

Control group 1 - Related controls

* Being aged 18 years or above;
* Close relative of the patient: relative defined as living in the same house as the CAP patient or daily contact;
* Is at the hospital at the moment of inclusion of the CAP patient or is willing to come for testing within 7 days;

Control group 2 - Unrelated healthy individuals

* Being aged 18 years or above;
* Subject with a preoperative appointment with the anaesthiologist for a planned surgical procedure;
* Age matched to a included CAP patient (+-10 years);
* Time matched to a included CAP patient (up to 14 days after inclusion of the CAP patient);
* Gender matched to a included CAP patient.

Control group 3 - Patients with stable COPD

* Being aged 18 years or above;
* Diagnosis of COPD confirmed with spirometry (GOLD criteria 2017)(76);
* Stable disease.

Control group 4 - Patients with exacerbation of COPD

* Being aged 18 years or above;
* Diagnosis of COPD confirmed with spirometry (GOLD criteria 2017)(76);
* Diagnosis of exacerbation of COPD: defined as an acute event characterised by a worsening of the patient's respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication (76).
* Presentation at emergency department with the suspicion of an exacerbation.

Exclusion Criteria:

In general:

* Recent pneumonia (\< 1 month) or pneumonia in last 3 months with known pneumococcal aetiology with one of current diagnostics;
* Was included in the study group before;
* Not capable of understanding information needed to sign informed consent.

Patients:

* Aspiration pneumonia;
* Hospitalisation for two or more days in the last 14 days;
* History of cystic fibrosis.

For all control groups:

* Fits inclusion criteria for patient group;
* Present or recent hospitalisation (14 days);
* Fits inclusion criteria for patient group;
* Use of antibiotics in the last 14 days, including maintenance antibiotic therapy.

Control group 1 and 2 - Related healthy controls and unrelated healthy individuals

* Active infectious respiratory complaints defined as defined as two or more respiratory symptoms (cough, nasal congestion, runny nose, sore throat or sneezes);
* Temperature \>38.0 ⁰C;
* Fits inclusion criteria for control group 3 or 4;
* Chronic pulmonary disease: COPD, asthma, cystic fibrosis, bronchiectasis.

Control group 3 - Patients with stable COPD

* Temperature \>38.0 ⁰C;
* Stable disease;
* Fits inclusion criteria for control group 4;
* Recent exacerbation (\<1 month) defined as increased respiratory symptoms with need of antibiotic and/or corticosteroid therapy;
* History of cystic fibrosis.

Control group 4 - Patients with exacerbation of COPD

* Current pneumonia;
* Recent exacerbation (\<1 month) defined as increased respiratory symptoms with need of antibiotic and/or corticosteroid therapy;
* Fits inclusion criteria for control group 3;
* History of cystic fibrosis.

Primary outcomes:
measure: qPCR diagnosed pneumococcal pneumonia
timeFrame: 1 day, day of inclusion
measure: Pneumococcal pneumonia with usual tests
timeFrame: 1 day, day of inclusion
Secondary outcomes:
measure: Number of DNA copies of S. pneumoniae in all lytA qPCR positive study subjects
timeFrame: 1 day, day of inclusion
measure: Occurrence of positive lytA qPCR at 30 days after inclusion in CAP patients
timeFrame: 30 days
measure: CURB-65 scores
timeFrame: 1 day, day of inclusion
measure: Procalcitonin
timeFrame: 1 day, day of inclusion
Other outcomes:
Locations:
city: Haarlem
country: Netherlands
facility: Spaarne Gasthuis
state: Noord-Holland
city: Alkmaar
country: Netherlands
facility: Noordwest Ziekenhuisgroep
Study officials:
affiliation: Noordwest Ziekenhuisgroep
name: Wim Boersma, MD. PhD.
role: PRINCIPAL_INVESTIGATOR
References: