Pneumonia Clinical Trial
Official title:
Procalcitonin Guided Antibiotic Therapy and Hospitalisation in Patients With Lower Respiratory Tract Infections: The "ProHOSP" Study
The aim of this study is to test if procalcitonin (PCT) guided antibiotic stewardship in patients with lower respiratory tract infection (LRTI) will be non-inferior, with at worst a 7.5% higher combined failure rate, as compared to standard care practice (current guidelines for LRTI) with reduced total antibiotic (AB) use and hospitalization rate and duration, respectively.
Background: Acute lower respiratory tract infections (LRTI), i.e. acute bronchitis and acute
exacerbations of chronic obstructive pulmonary disease (AECOPD), and community-acquired
pneumonia (CAP), employ important hospital resources and often unnecessary antibiotic (AB)
treatment courses. We demonstrated in four intervention trials enrolling > 1200 patients
that procalcitonin (PCT)-guidance markedly reduces AB prescription and duration. To
ascertain the external validity, safety and potential to improve the allocation of health
care resources, a non-inferiority multicenter intervention trial has to be done.
Aim: To compare a strategy based on evidence-based guidelines with PCT guided AB therapy in
LRTI with respect to outcome (combined disease-specific failure rates), use of AB and
hospital resources.
Design: Investigator-initiated, controlled trial with an open intervention. Patients
admitted with LRTI to hospital will be included and randomized 1:1 either to standard
management or to the PCT-guided prescription of AB. Randomization will be stratified by
centre (the hospital) and type of LRTI (Acute bronchitis/AECOPD/CAP).
Setting: Teaching hospitals and tertiary care clinics from northwestern and central
Switzerland.
Patients: 18 years or older, with LRTI of > 1 and < 28 days duration. Excluded are patients
without informed consent, not fluent in German, unlikely to comply, severe
immuno-suppression, terminal condition where death is expected to occur during the current
hospitalization, immediate need for intensive care.
Endpoints:
- Primary: Risk of combined disease-specific failure after 30 days.
- Secondary: AB exposure, side effects from ABs, time to AB treatment, rate and duration
of hospitalization, time to clinical stability, disease activity scores.
Endpoints will be assessed at baseline, daily in hospitalized patients and after 30 and 180
days by structured phone interviews by blinded medical students.
Intervention: Participating physicians will receive evidence-based guidelines for the
management of patients with LRTIs. Patients with LRTI will be randomized to PCT plus
guidelines ("PCT group") versus only guidelines-guided AB treatment ("control group"). In
patients randomized to the PCT group the use of ABs will be more or less discouraged (< 0.1
or < 0.25 ug/L) or encouraged (> 0.5 or > 0.25 ug/L), respectively. A re-evaluation after 6
to 24 hours in patients in whom antibiotics are withheld with worsening or non-improvement
of vital signs with PCT (< 0.1 or < 0.25 ug/L) is recommended. During hospitalization,
patients with AB treatment will be reassessed at day 3, 5 and 7 and in patients randomized
to the PCT group it is recommended to stop AB based on PCT levels. In AB-treated outpatients
or discharged patients with AECOPD and CAP randomized to the PCT group with uncomplicated
course, the recommended duration of AB therapy will be based on the last PCT level and will
be as follows: > 0.5 ug/L, 5 days; > 0.25 ug/L, 3 days; < 0.25 ug/L, stop AB.
Variables and measurement: Centers have to consecutively enroll all patients with LRTI.
Baseline data on medical history and clinical items, additional diagnostic tests,
co-morbidity, final prescribed treatment and reasons for hospital admission and stay will be
collected. After a pilot/feasibility phase of 3 months, study recruitment will continue from
Mar 2007 to Apr 2008.
Study hypothesis: PCT guidance will be non-inferior with at worst a 7.5% higher combined
failure rate as compared to standard care practice with a reduced total AB use and
hospitalization rate and duration, respectively.
Analyses: These will be done based on an intention-to-treat and a per-protocol principle.
With an assumed combined failure rate of 15% to 20%, a non-inferiority margin of 7.5%, a
maximum of 5% losses to follow-up, a value of 5% and power of 90%, the total sample size is
806 α one-sided to 1002.
Interim monitoring: Regular review of serious adverse events, quality and integrity of the
study by an independent data safety and monitoring board. Safety interim analysis and
blinded assessment (i.e., with both arms pooled) of the diagnostic and prognostic accuracy
of biomarkers after 50% of the patients recruited.
Ancillary projects: Six related projects will be performed alongside to this study
(including, cost-effectiveness, nursing and social influence on hospitalization, prognostic
value of novel biomarkers) to synergize scientific efforts.
Significance: Due to the high prevalence and absorption of hospital resources, this study
will offer the potential for large improvements in the management of LRTIs, along with
substantial reduction in hospitalization costs and AB resistance.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Diagnostic
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT04244474 -
Effect of Vitamin D Supplementation on Improvement of Pneumonic Children
|
Phase 1/Phase 2 | |
Completed |
NCT05815264 -
Clinical Trial of 23-valent Pneumococcal Polysaccharide Vaccine in Healthy Chinese Population Aged 2 Years and Above
|
Phase 1 | |
Recruiting |
NCT04589936 -
Prone Position to Improve Oxygenation in COVID-19 Patients Outside Critical Care
|
N/A | |
Completed |
NCT02905383 -
The Effect of Exercise on Physical Function and Health in Older People After Discharge From Hospital
|
N/A | |
Terminated |
NCT03944551 -
Bubble Continuous Positive Airway Pressure for Children With Severe Pneumonia in Mali, Africa
|
N/A | |
Completed |
NCT06210737 -
A Study to Evaluate Persistence of Immunity of PCV13 in Healthy Population Aged 2 Months,7 Months-5 Years
|
Phase 4 | |
Terminated |
NCT04660084 -
Impact of Molecular Testing on Improved Diagnosis, Treatment and Management of CAP
|
N/A | |
Not yet recruiting |
NCT05649891 -
Checklists Resuscitation Emergency Department
|
N/A | |
Withdrawn |
NCT05702788 -
Efficacy and Safety of Jaktinib in Participants With Severe Novel Coronavirus Pneumonia(COVID-19)
|
Phase 2 | |
Not yet recruiting |
NCT04171674 -
Pharmacokinetics of High-dose Ceftobiprole in Community-acquired Pneumonia Under Mechanical Ventilation.
|
N/A | |
Active, not recruiting |
NCT03140163 -
Screening for Pneumonia: A Comparison of Ultra Low Dose Chest CT [ULD-CT] and Conventional Chest Radiography [CXR]
|
N/A | |
Completed |
NCT02864420 -
Hospitalization at Home: The Acute Care Home Hospital Program for Adults
|
N/A | |
Completed |
NCT02638649 -
Prehospital Use of Ultrasound in Undifferentiated Shortness of Breath
|
||
Recruiting |
NCT02515565 -
Physiotherapy in Patients Hospitalized Due to Pneumonia.
|
N/A | |
Completed |
NCT02105298 -
Effect of Volume and Type of Fluid on Postoperative Incidence of Respiratory Complications and Outcome (CRC-Study)
|
N/A | |
Completed |
NCT01416519 -
Physiotherapy Technique Decreases Respiratory Complications After Cardiac Operation
|
N/A | |
Completed |
NCT01399723 -
Amoxicillin Versus Benzyl Penicillin for Treatment of Children Hospitalised With Severe Pneumonia
|
Phase 3 | |
Completed |
NCT01446926 -
Study of Investigational Pneumococcal Vaccine in Healthy Adults, Toddlers and Infants
|
Phase 1 | |
Completed |
NCT01416506 -
Community-Acquired Pneumonia (CAP) Surveillance
|
N/A | |
Completed |
NCT01476995 -
Prognostic Indicators as Provided by the EPIC ClearView
|
N/A |