Table 7 World Health Organization Trial Registration Data Set for PLUS-IS-LESS study

Primary Registry and Trial Identifying Number

www.ClinicalTrials.gov, NCT05463406

Date of Registration in Primary Registry

19 June 2022

Secondary Identifying Numbers

BASEC number 2022-00738

Trial Protocol version

Study protocol V3.0 dated 28.02.2023

Source(s) of Monetary or Material Support

Grant: SNSF 33IC30_201300

Primary Sponsor

CHUV

Secondary Sponsor(s)

Not applicable

Contact for Public Queries

NBB, noemie.boillat@chuv.ch

Contact for Scientific Queries

NBB, noemie.boillat@chuv.ch

Public Title

Procalcitonin and Lung Ultrasonography Guided Antibiotherapy in Emergency Departments, The PLUS-IS-LESS study

Scientific Title

Procalcitonin and Lung UltraSonography based antibiotherapy in patients with Lower rESpiratory tract infection in Swiss Emergency Departments: a pragmatic stepped-wedge cluster-randomized trial

Countries of Recruitment

Switzerland

Health Condition(s) or Problem(s) Studied

Lower respiratory tract infections

Intervention(s)

The PLUS clinical management algorithm: The PLUS algorithm starts with a validated pneumonia clinical prediction score (score of Van Vugt), followed by LUS. In case of positive results of any of these tests, PCT is measured to identify patients who will most likely benefit from antibiotics. A validated clinical severity score will ensure the safety of the intervention in those with discordant results (LUS consolidation and low PCT).

Usual care: management as usual

Key Inclusion and Exclusion Criteria

Inclusion Criteria:

• Patients aged 18 years or more

• Acute LRTI (acute illness, less than 21 days, with at least one lower respiratory tract symptom, i.e. cough, sputum, dyspnea, chest pain and no alternative explanation)

• At least one of the following clinical criteria:

◦ Focal abnormal auscultation (decreased breath sounds, crackles, bronchial breath sounds)

◦ Fever (documented temperature ≥ 38°C in the last 24 hours, including self-measured temperature ≥ 38°C)

◦ Tachypnea (respiratory rate ≥ 22/minute)

◦ Tachycardia (heart rate ≥ 100/minute)

Exclusion Criteria :

• Previous receipt of a quinolone, macrolide or ceftriaxone or, of more than one dose of any other antibiotic within 72h prior to enrolment (excepted prophylactic antibiotics or antibiotics given for urinary tract infection)

• Previous acute care hospital stay in the last 14 days

• Cystic fibrosis

• Severe COPD (≥GOLD 3 or if not available, as a proxy: exacerbation treated with antibiotics during the last 6 months)

• Severe immunodeficiency (drug-induced neutropenia with <500 neutrophils/mm3, HIV infection with CD4<200 cells/mm3, solid organ or bone marrow transplant recipient, prednisone ≥ 20mg/day for >28 days)

• Initial admission of the patient in the intensive care unit

• Microbiologically-documented SARS-CoV-2 (in the last 10 days)

• Lack of decision-making capacity

Study Type

Type: Investigator-initiated, interventional, pragmatic study

Allocation: Randomized

Intervention model: Stepped-wedge rollout

Masking: None (Open Label)

Primary purpose: Diagnostic

Phase: Phase IV

Date of First Enrollment

5 December 2022

Sample Size

1530 patients

Recruitment Status

Recruiting

Primary Outcome(s)

Safety outcome: Proportion of patients with clinical failure at day 28 (defined as a composite of any of the following: death or secondary ICU admission or secondary admission to hospital or hospital re-admission after index hospital discharge or complications due to the LRTI [empyema, lung abscess])

Efficacy outcome: Proportion of patients prescribed an antibiotic in each intervention group between enrolment and day 28

Key Secondary Outcomes

Quality of life measured with the community-acquired pneumonia symptom questionnaire on day 7, 28 and 90

Duration of ED stay in each study group

Rate and duration of hospitalization in each study group

Proportion of patients prescribed an antibiotic in each study group between enrolment and day 28.

Proportion of patients prescribed an antibiotic for a new respiratory infection in each study group between day 28 and 90.

Antibiotic side effects and C. difficile infection, from day 0 to 28

Acceptability and feasibility of the intervention through extensive identification of barriers and facilitators in patients and physicians conducting qualitative semi-structured interviews

Quality-adjusted life years (QALYs), derived from responses to the EQ-5D-5L questionnaire, in each group

Cost of the intervention as compared to usual care

Advanced automatic LUS image analysis method using machine learning to assist in LUS diagnosis and risk stratification.

Proportion of physician reaching proficiency in LUS image/video acquisition and interpretation after the training module.

Sensitivity, specificity and area under the ROC of physician “gestalt” and Van Vugt prediction score for CAP diagnosis

Ethics Review

Approved on 29.11.2022 (BASEC number 2022-00738).

Completion date

March 2025