Intravenous Versus Oral Treatment of the Main Acute Infections

Intravenous Versus Oral Treatment of the Main Acute Infections in Emergency Departments

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 Based on an extrapolated estimate from an unpublished local survey, approximately 50,000 patients in Denmark are admitted each year for infections and treated with IV antibiotics.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.

Study Overview

• Status: Recruiting
• Conditions: Respiratory Tract Infections; Cellulitis; Urinary Tract Infections
• Intervention / Treatment: Other: Oral treatment

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.

• Study Type: Interventional
• Enrollment (Estimated): 4000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Helene Skjøt-Arkil; Phone Number: +45 79971113; Email: hsa@rsyd.dk
• Study Contact Backup: Name: Mariana Bichuette Cartuliares; Phone Number: +45 79971113; Email: mbc@rsyd.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2400
    • Active, not recruiting
    • Bispebjerg and Frederiksberg Hospital
  • Copenhagen, Denmark
    • Recruiting
    • Nordsjællands Hospital
    • Contact: Jon Gitz Holler
  • Esbjerg, Denmark, 6700
    • Recruiting
    • Esbjerg and Grindsted Sygehus
    • Contact: Peter Biesenbach
  • Herlev, Denmark, 2730
    • Active, not recruiting
    • Herlev and Gentofte Hospital
  • Hvidovre, Denmark, 2650
    • Active, not recruiting
    • Amager and Hvidovre Hospital
  • Kolding, Denmark, 6000
    • Recruiting
    • Sygehus Lillebælt
    • Contact: Lone Wulff Madsen
  • Southern Denmark
    • Aabenraa, Southern Denmark, Denmark, 6200
      • Recruiting
      • Sygehus Sønderjylland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard Care; Standard intravenous treatment in accordance with local or national procedures
Active Comparator: Oral treatment	Other: Oral treatment; Patients randomized to oral treatment will commence the oral treatment immediately. The oral treatment is based on specially developed treatment suggestions developed by microbiologists and specialists in infectious diseases from the participating regions, and in respect with local treatment guidelines (detailed described in the protocol).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days alive outside hospital (Efficacy)	The number of days the patients are alive outside hospital within 30 days after randomization	From randomization date to 30 days
Number of patients requiring treatment with vasopressors	Number of patients that die or number of patients that require treatment with vasopressors within 30 days after randomization	From date of randomization to 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospital stay	Duration of hospital length of stay in days	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
Inhospital mortality	The number of death measured inhospital before discharge	From date of randomization until date of death in hospital from any cause, assessed up to 6 months
30-days mortality	The number of death within 30 days	up to 30 days from baseline (randomization date)
90-days mortality	The number of death within 90 days	Up to 90 days from baseline (randomization date)
One-year mortality	The number of death within one-year	Up to one-year from baseline (randomization date)
Five-year mortality	The number of death within five-years	Up to five-years from baseline (randomization date)
Discharge within 24 hours	The number of patients discharged within 24 hours	Up to 24 hours after rom baseline (randomization date)
Readmission	The number of patients readmitted to hospital	30 days after discharge date
Intensive care admission	Number of patients admitted to intensive care during current hospital stay	From date of randomization until date of admission to intensive care during hospitalization due to any cause, assessed up to 6 months
Days on antibiotic treatment within 30 days	Number of days the patient have been treated with antibiotics	Within 30 days from randomization date
Bacteremia	Number of patients diagnosed with bacteremia	Day 7 to day 30 from randomization date

Collaborators and Investigators

• Sponsor: University of Southern Denmark

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2025
• Primary Completion (Estimated): January 6, 2027
• Study Completion (Estimated): January 6, 2028

Study Registration Dates

• First Submitted: November 5, 2024
• First Submitted That Met QC Criteria: December 3, 2024
• First Posted (Actual): December 4, 2024

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Oral antibiotic therapy; intravenous antibiotic therapy; intravenous-to-oral-switch
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Infections; Respiratory Tract Diseases; Inflammation; Skin Diseases, Infectious; Suppuration; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Respiratory Tract Infections; Urinary Tract Infections; Cellulitis; Therapeutics
• Other Study ID Numbers: SHS-ED-1-2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No