Clinical trial NCT06715306: Intravenous Versus Oral Treatment of the Main Acute Infections
Official title: Intravenous Versus Oral Treatment of the Main Acute Infections in Emergency Departments
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Respiratory Tract Infections
Urinary Tract Infections
Cellulitis
Keywords: Oral antibiotic therapy
intravenous antibiotic therapy
intravenous-to-oral-switch
Lead sponsor: University of Southern Denmark
Sponsor class: OTHER
First posted: 2024-12-04
Enrollment: 4000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients admitted to the hospital with acute infections are often treated with intravenous (IV) antibiotics. Around 70% of these infections fall into three categories: respiratory tract infections, urinary tract infections, and cellulitis. A Danish study found that 76% of patients admitted with suspected community-acquired pneumonia and treated with antibiotics received them intravenously. Based on an extrapolated estimate from an unpublished local survey, approximately 50,000 patients in Denmark are admitted each year for infections and treated with IV antibiotics. The average hospital stay for these patients is 5.9 days, resulting in a total of 295,000 hospital days annually, accounting for about 7% of total hospital admissions in Denmark. This represents an annual cost of 2.3 billion DKK. While some patients need hospitalization due to their overall health or other serious conditions, others remain hospitalized primarily to receive IV antibiotics.

Expanding the use of oral antibiotics in emergency departments should be pursued only if it can demonstrate comparable efficacy and safety to IV administration. Therefore this study will investigate the efficiency of primarily oral antibiotics in acutely admitted patients with proven or suspected infections. Additionally, the investigators will evaluate the safety of oral regimen for these patients.

Detailed description: Patients admitted to the hospital with infections are often treated with intravenous antibiotics. The rationale for using intravenous antibiotics includes eliminating the risk of reduced absorption, achieving higher serum concentrations, and the fact that many broad-spectrum antibiotics (such as cephalosporins and carbapenems) are not available in oral form. However, intravenous antibiotics also have drawbacks, such as the risk of catheter-related infections, challenges in home-based treatment, and difficulty switching to oral antibiotics unless microbiological results are definitively positive. Prolonged hospital stays associated with intravenous antibiotic treatment lead to economic burdens, increased risk of hospital-acquired infections, and significant functional decline, especially in older patients.

In recent decades, many studies have explored the possibility of fully or partially replacing intravenous antibiotics with oral antibiotics for certain infections.

In this study, the investigators will examine the safety and efficacy of primarily oral antibiotic regimens in patients with confirmed or suspected infections admitted to the emergency department. The study is an open-label, prospective, randomized controlled trial. Participants will be randomly assigned to receive either standard intravenous antibiotic treatment according to Danish guidelines or oral antibiotic treatment based on tailored recommendations developed by microbiologists and infectious disease specialists at participating sites, in accordance with local guidelines.

The study has two primary outcomes: 1) Efficacy-measured as the number of days alive outside the hospital within 30 days after randomization, and 2) Safety-measured by mortality or the need for vasopressors within 30 days after randomization. A total of 4,000 patients will be needed to address both primary outcomes.

Aim: The trial aims to investigate the safety and efficacy of oral antibiotic administration compared to intravenous antibiotic administration in patients referred to the emergency department with suspected or diagnosed bacterial pneumonia, urinary tract infection and cellulitis.

Eligibility criteria: Inclusion Criteria:

* Suspected respiratory tract infection, urinary tract infection, or cellulitis by the attending physician
* Planned or initiated intravenous antibiotic treatment

Exclusion Criteria:

* if received more than two doses of intravenous antibiotics;
* systolic blood pressure \<90 mmHg;
* nausea and/or vomiting in more than one short-term instance during the last 2 days;
* suspected significantly reduced gastrointestinal absorption;
* confirmed plasma-lactate \> 2;
* pregnant or nursing;
* unable to give informed consent;
* severe immunodeficiency;
* urgent vital treatment needed.

Primary outcomes:
measure: Days alive outside hospital (Efficacy)
timeFrame: From randomization date to 30 days
measure: Number of patients requiring treatment with vasopressors
timeFrame: From date of randomization to 30 days
Secondary outcomes:
measure: Length of hospital stay
timeFrame: From date of randomization until date of documented hospital discharge or date of death from any cause, whichever came first, assessed up to 6 months
measure: Inhospital mortality
timeFrame: From date of randomization until date of death in hospital from any cause, assessed up to 6 months
measure: 30-days mortality
timeFrame: up to 30 days from baseline (randomization date)
measure: 90-days mortality
timeFrame: Up to 90 days from baseline (randomization date)
measure: One-year mortality
timeFrame: Up to one-year from baseline (randomization date)
measure: Five-year mortality
timeFrame: Up to five-years from baseline (randomization date)
measure: Discharge within 24 hours
timeFrame: Up to 24 hours after rom baseline (randomization date)
measure: Readmission
timeFrame: 30 days after discharge date
measure: Intensive care admission
timeFrame: From date of randomization until date of admission to intensive care during hospitalization due to any cause, assessed up to 6 months
measure: Days on antibiotic treatment within 30 days
timeFrame: Within 30 days from randomization date
measure: Bacteremia
timeFrame: Day 7 to day 30 from randomization date
Other outcomes:
Locations:
city: Aabenraa
country: Denmark
facility: Sygehus Sønderjylland
state: Southern Denmark
Study officials:
References: