Antibiotics for Delirium in Older Adults With No Clear Urinary Tract Infection (A-DONUT)

Delirium is an acute confusional state that is experienced by many older adults who are admitted to hospital. To treat delirium the underlying cause needs to be identified promptly, but this is challenging. One of the potential causes of delirium is infection. Urine tests show that most patients experiencing delirium have bacteria in their urine, however, bacteria in the urine is common among older adults, and does not automatically indicate an infection is present. As a result it is difficult to know whether a lower urinary tract infection is present as individuals with delirium are frequently unable to report clinical signs of infection - symptoms of pain or discomfort with urination, having to urinate more frequently or pelvic discomfort. Very often, individuals with delirium are treated with antibiotics despite the fact that it is unknown whether antibiotics help to improve delirium in cases where bacteria in the urine is present. This proposed study is a randomized controlled trial that will examine if adults (age 60 or older) with delirium and suspected infection benefit from taking antibiotics.

Study Overview

• Status: Recruiting
• Conditions: Infectious Disease
• Intervention / Treatment: Drug: Start Antibiotics / Continue Antibiotics for treatment of bacteriuria; Other: No Antibiotics for treatment of bacteriuria

• Study Type: Interventional
• Enrollment (Estimated): 550
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michael Fralick, MD; Phone Number: (416) 586-4800; Email: mike.fralick@mail.utoronto.ca

Study Locations

• Canada
  • Ontario
    • Sault Ste. Marie, Ontario, Canada
      • Recruiting
      • Sault Area Hospital
      • Contact: Lucas Castellani

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria

• Age ≥ 60 and admitted to a hospital ward (including rehabilitation hospital);
• Active delirium (defined by CAM: [1] inattention AND [2] acute and fluctuating level of consciousness, and either [3] disorganized thinking OR [4] altered mental status; or defined by the 4AT score [www.the4at.com/]) OR physician's diagnosis
• Less than 24 hours of antibiotics (prior to trial assessment)
• Either pyuria (defined as white blood cells detected on urinalysis or dipstick) or bacteriuria (defined as bacteria growing on urine culture)

Exclusion criteria

• Fever (temperature > 37.9C or > 100.2F) in the past 48 hours;
• Signs of lower urinary tract infection symptoms (such as new dysuria) or upper urinary symptoms (such as costovertebral tenderness)
• In the opinion of the treating physician, there is a reason apart from delirium and urine test results to treat with antibiotics (e.g., pneumonia)
• Indwelling urinary catheter for > 72 hours

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
Other: Antibiotics; Participants will be randomized to start or continue with antibiotics. Antibiotic type and duration targeted to lower urinary tract infection as directed by the Most Responsible Physician (MRP).	Drug: Start Antibiotics / Continue Antibiotics for treatment of bacteriuria; Participants will be randomized to start or continue with antibiotics (with antibiotic duration determined by the Most Responsible Physician [MRP]). Antibiotics choice to be selected by the MRP.
Other: No Antibiotics; Participants will be randomized to no antibiotics	Other: No Antibiotics for treatment of bacteriuria; Participants will be randomized to no antibiotics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delirium at day 7 or at day of hospital discharge, whichever is earliest	Delirium will be assessed using Confusion Assessment Method (CAM) or 4 A's Test (4AT). CAM assesses 4 delirium features: [1] inattention, [2] acute and fluctuating level of consciousness, [3] disorganized thinking and [4] altered mental status. For a diagnosis of delirium by CAM, the patient must display feature [1] AND [2], AND EITHER [3] or [4]. The 4AT is scored from 0-12. A score of 4 or more suggests delirium.	Delirium will be assessed at the first of day 7 or discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospitalization		Up to 30 days
Number of participants with bacteremia (bacteria isolated in blood culture)		Up to 7 days
Number of participants who were transferred to Intensive Care Unit (ICU)		Up to 7 days
Number of participants who had a fall		Up to 7 days
Number of participants who were physically restrained		Up to 7 days
Number of participants who received antipsychotics		Up to 7 days
Days of antibiotics		Up to 7 days
Number of participants with C. difficile infection	C. difficile will be defined as a combination of a positive microbiological test for C. difficile (if still hospitalized at the time of diagnosis), or self-reported diagnosis of C. difficile (provided the patient reported diarrhea and receipt of an antibiotic to treat C. difficile)	By 30 days
Number of participants who died		By 30 days
Number of participants who died		By 365 days
Number of participants who were readmitted to hospital		By 365 days
Number of participants who were readmitted to hospital		By 30 days

Collaborators and Investigators

• Sponsor: Mount Sinai Hospital, Canada
• Collaborators: Unity Health Toronto; The Ottawa Hospital; Sault Area Hospital; Michael Garron Hospital
• Investigators: Principal Investigator: Michael Fralick, MD, PhD, Sinai Health System; Principal Investigator: Chris Kandel, MD, PhD, Michael Garron Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: July 24, 2023
• First Submitted That Met QC Criteria: August 21, 2023
• First Posted (Actual): August 22, 2023

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Antibiotics; Older adults; Urinary Tract Infection; Delirium
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Urologic Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Disease Attributes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Delirium; Infections; Communicable Diseases; Urinary Tract Infections; Anti-Infective Agents; Antitubercular Agents; Anti-Bacterial Agents; Antibiotics, Antitubercular
• Other Study ID Numbers: CTO 4466

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