Quantitative Polymerase Chain Reaction for Improved Detection of Pneumococci in CAP "CAPTAIN"

Medical Center Alkmaar

Status: Completed

Conditions: Community-acquired Pneumonia; Pneumonia, Pneumococcal

Treatments: Diagnostic Test: LytA targeted quantitative polymerase chain reaction (qPCR)

Study type: Observational

Funder types: Other

Identifiers

NCT03315403

63200

Details and patient eligibility

About

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.

Enrollment: 922 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

922 participants in 5 patient groups

Patients with CAP

Description:

Patients with a diagnosis of radiographically-confirmed CAP at the emergency department will undergo the usual diagnostics. For the study an extra nasopharynx sample, saliva sample and blood sample will be collected. A questionnaire will be filled in. LytA qPCR and cultures will be performed on samples of the upper respiratory tract (nasopahrynx, oropharynx, saliva, sputum if available)

Treatment:

Diagnostic Test: LytA targeted quantitative polymerase chain reaction (qPCR)

Related controls

Description:

Of related controls a nasopharynx sample, oropharynx sample and saliva sample will be collected. A questionnaire will be filled in. LytA qPCR and cultures will be performed on samples of the upper respiratory tract (nasopahrynx, oropharynx, saliva)

Treatment:

Diagnostic Test: LytA targeted quantitative polymerase chain reaction (qPCR)

Unrelated controls

Description:

Of unrelated controls a nasopharynx sample, oropharynx sample and saliva sample will be collected. A questionnaire will be filled in. LytA PCR and cultures will be performed on samples of the upper respiratory tract (nasopahrynx, oropharynx, saliva)

Treatment:

Diagnostic Test: LytA targeted quantitative polymerase chain reaction (qPCR)

Patients with stable COPD

Description:

Of stable COPD patients a nasopharynx sample, oropharynx sample and saliva sample will be collected. And if available also a sputum sample. A questionnaire will be filled in. LytA qPCR and cultures will be performed on samples of the upper respiratory tract (nasopahrynx, oropharynx, saliva, sputum if available)

Treatment:

Diagnostic Test: LytA targeted quantitative polymerase chain reaction (qPCR)

Patients with exacerbation of COPD

Description:

Of patients with a diagnosis of an exacerbation of COPD at the emergency department a nasopharynx sample, oropharynx sample and saliva sample will be collected apart from the usual diagnostics. If available also a sputum sample will be collected. A questionnaire will be filled in. LytA qPCR and cultures will be performed on samples of the upper respiratory tract (nasopahrynx, oropharynx, saliva, sputum if available)

Treatment:

Diagnostic Test: LytA targeted quantitative polymerase chain reaction (qPCR)