Clinical trial NCT04595526: Optimal Collection of Specimens of the Lower Respiratory Tract
Official title: Optimal Collection of Specimens of the Lower Respiratory Tract
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Respiratory Tract Infections
Lead sponsor: University of Southern Denmark
Sponsor class: OTHER
First posted: 2020-10-20
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Respiratory tract infection is a serious condition causing 3 million deaths worldwide every year. Approximately 20-40% of patients with community-acquired pneumonia are hospitalised. Treatment of pneumonia should be initiated as quickly as possible and therefore an early and precise diagnostic is extremely important. Imprecise or delayed diagnosis often results in overconsumption of broad-spectrum antibiotics that contribute to the development of antibiotic resistance. Unspecific symptoms, unsure diagnosis methods and a wait time of up to several days for results challenge a quick and effective diagnosis and treatment of pneumonia. Microbiological analysis of sputum samples is used to identify pathogens causative to pneumonia. However, obtaining specimens of good quality is challenging and affects the sensitivity and specificity of the results. Therefore, the identification of the optimal sputum collecting method is needed to ensure an improved identification process of the pathogen causing pneumonia.

The purpose of this study is to determine the most optimal method for obtaining good quality sputum samples when comparing tracheal suction to methods without suction. A more accurate diagnosis will lead to more appropriate antibiotic consumption and will reduce the general development of antibiotic resistance.

Detailed description: Multi-resistant bacteria (MRB) are associated with high antibiotic consumption and designated by WHO as one of the major threats to the world. In Denmark, the incidence of MRB is generally increasing, and every 20th patient admitted to Danish Emergency Department (ED), is infected with resistant bacteria. Respiratory tract infection is a serious condition, with 3 million death worldwide every year, and about 20-40% of the patients with community-acquired pneumonia need hospitalization. Data from the ED at Hospital Sønderjylland shows that 6% of the patients are registered with a respiratory tract infection, including pneumonia. Treatment of pneumonia should be initiated within a few hours, therefore early and precise diagnostic is extremely important. An imprecise or delayed diagnostic will often result in overconsumption of broad-spectrum antibiotics, contributing to an increase in the development of MRB threatening future treatments possibilities. Currently, pneumonia diagnosis is based on clinical symptoms such as cough, expectoration, chest pain, fever or breathlessness, combined with an x-ray of the lungs, relevant blood tests and microbiological analyses of sputum samples. However, X-ray is an imprecise diagnostic tool, and sputum test responses are first available after 2 days. Thus, the diagnostic is challenged by unspecific symptoms, unsure diagnostic methods and prolonged waiting time for results of up to several days. Sputum can be cultivated to determine the bacterial agent. However, the sputum samples are often of poor quality and many patients cannot deliver a sample. A recently published Danish study shows, that only half of the patients at the ED have sputum samples collected for culturing and none of them had their antibiotic treatment adjusted based on the microbiological results of the sputum. Despite, the use of different microbiological analysis methods to detect bacteria or virus causative of pneumonia, common to the methods is that a representative specimen from the lower respiratory tract is crucial for optimal sensitivity and specificity. Despite technological advances in molecular diagnostics, identifying the etiology of pneumonia remains a challenge. Consequently, identification of optimal sputum collecting method and investigation of an alternative sputum analyses assessment is needed to improve specimens' suitability to identify the etiology of pneumonia.

Clinical experience indicates that an inhalation mask with saline solution can induce a successful sputum sampling. Tracheal suction is often used on intubated patients in the intensive care unit to collect sputum, and this method has become the standard procedure at several ED. A comparison of the two methods has not been investigated in an ED context nor has the quality of the collected sputum samples and relevance for clinical practice been explored.

Ensuring the optimal sputum collection is of particular relevance during the COVID-19 pandemic. An optimal sputum collection is important to be able to determine if the pneumonia is caused by SARS-CoV-2 or a bacterium - especially in situations where the swab from throat or pharynx presents a negative result, as the method is not sensitive enough to rule out COVID-19 in patients with pneumonia. Accordingly, the Health Board in Denmark recommends tracheal suction of patients admitted with suspected COVID-19 in case of symptoms of the lower respiratory tract, and only in cases the symptoms originates from the upper airways a swab can be performed

1.1 Hypothesis and purpose The hypotheses is that methods without suction (forced expiratory technique and induced sputum) are just as effective as tracheal suction for obtaining a representative specimen from the lower respiratory tract..

The purpose of this study is to determine the most optimal method for obtaining high-quality sputum samples.

Following research questions will be explored:

1. What is the difference between the conventional sampling by tracheal suction comparing to sampling using forced expiratory or induced sputum techniques in relation to the suitability of collected specimens from the lower respiratory tract
2. Identification of possible adverse events during sputum collection
3. How do patients experience the two sputum sample collecting procedures?

Collection of sputum and adverse events After consent, the patient will be randomized in two groups with 1:1 allocation using permuting blocks. The software tool 'Randomized' offered by Open Patient data Explorative Network (OPEN) will be used.

ORGANIZATION The project is anchored in the Research unit of Emergency Medicine, the ED of Hospital Sønderjylland and the Department of Regional Health Research, University of Southern Denmark. The project is a research collaboration between clinicians and researchers in the field of emergency medicine and microbiology at Hospital Sønderjylland (SHS) and Odense University Hospital (OUH).

Eligibility criteria: Inclusion Criteria:

* Patients admitted with suspected lower respiratory tract infection
* Patients \> 18 years old
* One of the following symptoms: dyspnea, cough, expectoration, fever and chest tightness

Exclusion Criteria:

* Patients transferred directly to ICU
* If the attending physician considers emergency treatment is needed
* Patients receiving prednisolone treatment of 20mg/day or more over the last 2 weeks
* Patient which consent cannot be obtained

Primary outcomes:
measure: Quality of specimen from the lower respiratory tract
timeFrame: From collection to culture results - up to 5 days
Secondary outcomes:
measure: Patient clinical symptoms
timeFrame: Patients are followed before intervention and 10 minutes after intervention
measure: Respiratory rate
timeFrame: Measured twice: Baseline ( at admission) and follow up (10 minutes after intervention)
measure: Oxygen saturation
timeFrame: Measured twice: Baseline ( at admission) and follow up (10 minutes after intervention)
measure: Patient well-being and experience of procedure
timeFrame: Measured twice: Baseline ( at admission) and follow up (10 minutes after intervention)
measure: Occurrence of side effects
timeFrame: Registered up to 1 hour after intervention
measure: Short term mortality
timeFrame: Registered within 7 days from hospital admission
measure: Number of patients readmitted to hospital
timeFrame: Registered within 1 month after readmission
measure: Patient experience of sputum collection
timeFrame: Measured 5 minutes after procedure
Other outcomes:
Locations:
city: Aabenraa
country: Denmark
facility: Hospital of Southern Jutland
Study officials:
affiliation: University Hospital of Southern Denmark
name: Christian Backer Mogensen, MD PhD
role: STUDY_CHAIR
References:
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citation: Cartuliares MB, Skjot-Arkil H, Rosenvinge FS, Mogensen CB, Skovsted TA, Pedersen AK. Effectiveness of expiratory technique and induced sputum in obtaining good quality sputum from patients acutely hospitalized with suspected lower respiratory tract infection: a statistical analysis plan for a randomized controlled trial. Trials. 2021 Oct 2;22(1):675. doi: 10.1186/s13063-021-05639-1.