Seven vs. 14 Days Treatment for Male Urinary Tract Infection

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Seven Versus Fourteen Day Treatment for Male Urinary Tract Infection

Conditions
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Urinary Tract Infections

Intervention / Treatment
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* Other: Longer therapy duration
* Other: Shorter therapy duration


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Longer (14 day) duration antimicrobial treatment<br>14 days of ciprofloxacin or trimethoprim/sulfamethoxazole | Other: Longer therapy duration<br>* 14 days of antimicrobial treatment<br>|
| Placebo Comparator: Shorter (7 day) duration antimicrobial treatment<br>7 days of ciprofloxacin or trimethoprim/sulfamethoxazole, followed by 7 days of placebo | Other: Shorter therapy duration<br>* 7 days of antimicrobial treatment<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urinary Tract Infections, Urinary antiinfective agents