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

NCT03315403 | Completed

• 1 other identifier: 63200
• Study Type: observational
• Target: 922
• Locations: 1 country
• Sites: 2

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.

Conditions

Pneumonia, Pneumococcal; Community-acquired Pneumonia

Keywords

quantitative polymerase chain reaction; qPCR; autolysin; lytA; Pneumococcal pneumonia; Diagnostics; Community-acquired Pneumonia; Antibiotic resistance

Outcome Measures

Primary Outcomes (2)

• qPCR diagnosed pneumococcal pneumonia

  Occurrence of qPCR proven pneumococcal pneumonia (CAP with S. pneumoniae detected by qPCR in at least one of the samples with a positive lytA qPCR and a DNA copy number above the determined cut-off value) using the cut-off value in at least one of the specimens at inclusion. The cut-off value will be determined in this study, see secondary objective.

  1 day, day of inclusion

• Pneumococcal pneumonia with usual tests

  Occurrence of pneumococcal pneumonia proven by at least one of the routine microbiological tests (urine antigen test, blood culture and/or sputum culture). The difference between outcome measure 1 and 2 is the added diagnostic value.

  1 day, day of inclusion

Secondary Outcomes (4)

• Number of DNA copies of S. pneumoniae in all lytA qPCR positive study subjects

  1 day, day of inclusion

• Occurrence of positive lytA qPCR at 30 days after inclusion in CAP patients

  30 days

• CURB-65 scores

  1 day, day of inclusion

• Procalcitonin

  1 day, day of inclusion

Study Arms (5)

Patients with CAP

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)

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

Related controls

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)

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

Unrelated controls

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)

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

Patients with stable COPD

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)

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

Patients with exacerbation of COPD

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)

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

Interventions

LytA targeted quantitative polymerase chain reaction (qPCR) DIAGNOSTIC_TEST

LytA qPCR and cultures will be performed on samples of the upper respiratory tract (nasopahrynx, oropharynx, saliva, sputum if available)

Patients with CAP; Patients with exacerbation of COPD; Patients with stable COPD; Related controls; Unrelated controls

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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)

You may qualify if:

• 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:
• New or worsened coughing;
• Production of purulent sputum or change in sputum colour;
• Temperature \>38.0 ⁰C or ≤36.0 ⁰C (tympanic);
• Auscultatory findings consistent with pneumonia, including rales, evidence of pulmonary consolidation (dullness on percussion, bronchial breath sounds, rales, or egophony), or both;
• White blood cell count of \>10x10\^9 cells/L or \<4x10\^9 cells/L or \>15% bands;
• C-reactive protein level ≥30mg/L;
• 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;

You may not qualify if:

• 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:
• Present or recent hospitalisation (14 days);
• 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;
• Chronic pulmonary disease: COPD, asthma, cystic fibrosis, bronchiectasis.

Sponsors & Collaborators

• Medical Center Alkmaar: lead

Study Sites (2)

Spaarne Gasthuis

Haarlem, North Holland, Netherlands

Location

Noordwest Ziekenhuisgroep

Alkmaar, Netherlands

Location

Biospecimen

Retention: SAMPLES WITH DNA

Collection of nasopharynx, oropharynx, saliva, sputum and blood.

MeSH Terms

Conditions

Pneumonia, Pneumococcal; Community-Acquired Pneumonia

Condition Hierarchy (Ancestors)

Pneumococcal Infections; Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pneumonia, Bacterial; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Community-Acquired Infections

Study Officials

• Wim Boersma, MD. PhD.

  Noordwest Ziekenhuisgroep

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD. PhD. Pulmonologist

Study Record Dates

• First Submitted: October 3, 2017
• First Posted: October 20, 2017
• Study Start: April 5, 2018
• Primary Completion: March 12, 2020
• Study Completion: March 12, 2020
• Last Updated: April 8, 2022

Record last verified: 2022-04

Locations

NL (2)