Seven vs. 14 Days Treatment for Male Urinary Tract Infection

Seven Versus Fourteen Day Treatment for Male Urinary Tract Infection

This study will investigate the treatment of urinary tract infection in men. Specifically, the investigators are looking to see if shorter duration of antibiotics (7 days) is any worse than longer duration of antibiotics (14 days). The investigators will also study whether longer treatment leads to an increase in antibiotic resistant bacteria in the large intestine (colon), or an increase in drug side effects.

Study Overview

• Status: Completed
• Conditions: Urinary Tract Infections
• Intervention / Treatment: Other: Longer therapy duration; Other: Shorter therapy duration

Detailed Description

The proposed study is a randomized placebo-controlled trial of treatment duration for male urinary tract infection (UTI). Specifically, 319 men with a UTI will be randomized to 7 vs. 14 days of antimicrobial treatment. The primary outcome is resolution of UTI symptoms, assessed 14 days after completing active antimicrobial treatment. Secondary outcomes include recurrent UTI in the 4 weeks after treatment, adverse drug events, and intestinal carriage of antimicrobial resistant Gram-negative bacilli. Subjects will be enrolled from the Primary Care Clinic and Emergency Department at the Minneapolis VA Medical Center (MVAMC).

Currently, the optimal treatment duration for male UTI is unknown. A clinical trial of 14 vs. 28 days of treatment showed no difference in outcomes, whereas another trial of 3 vs.14 days showed an increase in recurrence with 3 days of treatment. However, current treatment recommendations are to treat men with UTI for 7 to 14 days, and no data exist to favor the shorter or longer duration. Most men with UTI in the VA are treated for more than 7 days, which is associated with a small but significant increase in Clostridium difficile infection. Additionally, other studies of non-UTI infectious diseases have shown that longer-duration treatment leads to increased antimicrobial resistance. Longer-duration treatment is also more costly and inconvenient to patients. Thus, since longer-duration treatment is associated with some adverse outcomes, in order to justify longer-duration treatment thee must be some clinically significant benefit to the extended treatment.

Accordingly, the proposed randomized placebo-controlled trial of 319 men with UTI will test the hypothesis that 7 days of antimicrobial treatment is non-inferior for the resolution of UTI symptoms when compared to 14 days of treatment. This study will provide valuable information to VA patients and clinicians regarding a common and understudied clinical decision.

• Study Type: Interventional
• Enrollment (Actual): 273
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis VA Health Care System, Minneapolis, MN
  • Texas
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey VA Medical Center, Houston, TX

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

Must have all

• Male gender
• New-onset (within 7 days) of at least one of the following symptoms/findings: dysuria, urinary frequency, urgency, hematuria, perineal pain, supra-pubic pain, costovertebral angle tenderness, or flank pain
• Treated as an outpatient (Primary Care Center or Emergency Department), with < 24 hours observation in the hospital or Emergency Department following the time of initial diagnosis
• Prescribed treatment with at least 7 days, but not more than 14 days, of either ciprofloxacin or TMP-SMZ

Exclusion Criteria:

Must have none

• Admission to the hospital (for > 24h) at the time of diagnosis
• Documented fever at time of initial evaluation ( 38.0 Celsius)
• Previous enrollment in the study
• Treatment for UTI in past 14 days
• Not able to give informed consent
• Unwilling to return for study visit
• Symptoms thought more likely to be caused by a non-UTI diagnosis (e.g., urinary calculus, sexually transmitted infection, etc.)
• Other antimicrobial therapy (new or ongoing) prescribed for a non-UTI diagnosis (e.g., cellulitis, pneumonia, etc.)
• Treatment initiated with an empiric antimicrobial to which the organism isolated in the urine culture is non-susceptible based on standard laboratory criteria
• Treatment initiated with an empiric antimicrobial regimen that is underdosed, based on current guidelines and reviews

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Longer (14 day) duration antimicrobial treatment; 14 days of ciprofloxacin or trimethoprim/sulfamethoxazole	Other: Longer therapy duration; 14 days of antimicrobial treatment
PLACEBO_COMPARATOR: Shorter (7 day) duration antimicrobial treatment; 7 days of ciprofloxacin or trimethoprim/sulfamethoxazole, followed by 7 days of placebo	Other: Shorter therapy duration; 7 days of antimicrobial treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resolution of UTI Symptoms 14 Days After Completing Active Antimicrobial Therapy	This outcome will be assessed in a binary manner. Subjects with persistent UTI symptoms or having received further antimicrobials because of UTI symptoms will be considered to have not met the primary outcome, whereas those without persistent UTI symptoms and not having received further antimicrobials will be considered to have met the primary outcome.	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrent UTI Within 28 Days of Completing Active Study Medication	New onset of symptomatic UTI within the 28 day follow-up period	28 days
Adverse Drug Event in the 28 Days After Completing Study Medication	The incidence of adverse drug events, including nausea, vomiting, diarrhea, dizziness, headache, drug allergy, and C. difficile infection, both individually and in aggregate, will be compared between treatment groups This outcome is number of subjects experiencing ANY adverse drug event	28 days
Intestinal Carriage of Antimicrobial-resistant Gram Negative Bacilli	Intestinal carriage of antimicrobial-resistant Gram-negative bacilli after completing study medication, as compared to a baseline sample taken early in treatment. Antimicrobial resistance for this measure was defined as newly detected resistance to either of the study drugs, ciprofloxacin or trimethoprim/sulfamethoxazole.	7 days

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Dimitri M Drekonja, MD, Minneapolis VA Health Care System, Minneapolis, MN

Publications and helpful links

General Publications

• Drekonja DM, Trautner B, Amundson C, Kuskowski M, Johnson JR. Effect of 7 vs 14 Days of Antibiotic Therapy on Resolution of Symptoms Among Afebrile Men With Urinary Tract Infection: A Randomized Clinical Trial. JAMA. 2021 Jul 27;326(4):324-331. doi: 10.1001/jama.2021.9899.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 24, 2014
• Primary Completion (ACTUAL): December 31, 2019
• Study Completion (ACTUAL): December 31, 2019

Study Registration Dates

• First Submitted: November 19, 2013
• First Submitted That Met QC Criteria: November 19, 2013
• First Posted (ESTIMATE): November 25, 2013

Study Record Updates

• Last Update Posted (ACTUAL): June 2, 2021
• Last Update Submitted That Met QC Criteria: May 13, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Urinary Tract Infections; Urinary antiinfective agents
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Infections; Communicable Diseases; Urinary Tract Infections; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Respiratory System Agents; Sympathomimetics; Vasoconstrictor Agents; Nasal Decongestants; Oxymetazoline
• Other Study ID Numbers: CLIN-008-13S; I01BX007080 (OTHER_GRANT: VA Merit Review)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: No formal plan submitted at time of grant. Will handle such requests on a case-by-case basis with input from local privacy officer and institutional review board.
• IPD Sharing Time Frame: Anticipate will share data for 2 years after publication of the primary result manuscript
• IPD Sharing Access Criteria: Requests will be handled on a case-by-case basis with input from the local privacy officer and IRB.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No