Seven vs. 14 Days Treatment for Male Urinary Tract Infection

• ClinicalTrials.gov Identifier: NCT01994538
• Recruitment Status: Completed
• First Posted: November 25, 2013
• Results First Posted: October 28, 2020
• Last Update Posted: October 28, 2020
• Sponsor: VA Office of Research and Development
• Information provided by (Responsible Party): VA Office of Research and Development

Tracking Information

• First Submitted Date: November 19, 2013
• First Posted Date: November 25, 2013
• Results First Submitted Date: October 2, 2020
• Results First Posted Date: October 28, 2020
• Last Update Posted Date: October 28, 2020
• Actual Study Start Date: April 24, 2014
• Actual Primary Completion Date: December 31, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 19, 2013)

Resolution of UTI Symptoms 14 Days After Completing Active Antimicrobial Therapy [ Time Frame: 14 days ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 2, 2020)

• Recurrent UTI Within 28 Days of Completing Active Study Medication [ Time Frame: 28 days ]
  New onset of symptomatic UTI within the 28 day follow-up period
• Adverse Drug Event in the 28 Days After Completing Study Medication [ Time Frame: 28 days ]
  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
• Intestinal Carriage of Antimicrobial-resistant Gram Negative Bacilli [ Time Frame: 7 days ]
  Intestinal carriage of antimicrobial-resistant Gram-negative bacilli after completing study medication, as compared to a baseline sample taken early in treatment.

Original Secondary Outcome Measures (submitted: November 19, 2013)

• Recurrent UTI Within 28 Days of Completing Active Study Medication [ Time Frame: 28 days ]
  New onset of symptomatic UTI within the 28 day follow-up period
• Adverse Drug Event in the 28 Days After Completing Study Medication [ Time Frame: 28 days ]
  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
• Intestinal Carriage of Antimicrobial-resistant Gram Negative Bacilli [ Time Frame: 7 days ]
  Intestinal carriage of antimicrobial-resistant Gram-negative bacilli after completing study medication, as compared to a baseline sample taken early in treatment.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Seven vs. 14 Days Treatment for Male Urinary Tract Infection
• Official Title: Seven Versus Fourteen Day Treatment for Male Urinary Tract Infection
• Brief Summary: 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

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
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Urinary Tract Infections

Intervention

• Other: Longer therapy duration
  14 days of antimicrobial treatment
• Other: Shorter therapy duration
  7 days of antimicrobial treatment

Study Arms

• Active Comparator: Longer (14 day) duration antimicrobial treatment
  14 days of ciprofloxacin or trimethoprim/sulfamethoxazole
  Intervention: Other: Longer therapy duration
• Placebo Comparator: Shorter (7 day) duration antimicrobial treatment
  7 days of ciprofloxacin or trimethoprim/sulfamethoxazole, followed by 7 days of placebo
  Intervention: Other: Shorter therapy duration

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 29, 2020): 273
• Original Estimated Enrollment (submitted: November 19, 2013): 319
• Actual Study Completion Date: December 31, 2019
• Actual Primary Completion Date: December 31, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Study of UTI in men

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01994538
• Other Study ID Numbers: CLIN-008-13S; I01BX007080 ( Other Grant/Funding Number: VA Merit Review )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Analytic Code
• Time Frame: Anticipate will share data for 2 years after publication of the primary result manuscript
• Access Criteria: Requests will be handled on a case-by-case basis with input from the local privacy officer and IRB.

• Responsible Party: VA Office of Research and Development
• Study Sponsor: VA Office of Research and Development
• Collaborators: Not Provided

Investigators

• Principal Investigator: Dimitri M Drekonja, MD; Minneapolis VA Health Care System, Minneapolis, MN

• PRS Account: VA Office of Research and Development
• Verification Date: October 2020