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

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Urinary Tract Infections
• Interventions: Other: Longer therapy duration; Other: Shorter therapy duration
• Enrollment: 273

Participant Flow

Recruitment Details	Enrolled subjects are afebrile men with symptomatic urinary tract infection who were initially treated with 7-14 days of trimethoprim/sulfamethoxazole (TMP/SMZ) or ciprofloxacin by the treating clinician. Subjects were randomized prior to day 8 of treatment to an additional 7 days of their original study drug (14d group) or placebo (7d group.
Pre-assignment Details	Primary analysis was per-protocol, and included all subjects who took at least 26 of 28 doses of medication. Intention to treat analysis includes all randomized subjects.

Arm/Group Title	Longer (14 Day) Duration Antimicrobial Treatment	Shorter (7 Day) Duration Antimicrobial Treatment
Arm/Group Description	14 days of ciprofloxacin or trimethoprim/sulfamethoxazole Longer therapy duration: 14 days of antimicrobial treatment	7 days of ciprofloxacin or trimethoprim/sulfamethoxazole, followed by 7 days of placebo Shorter therapy duration: 7 days of antimicrobial treatment
Period Title: Overall Study
Started [1]	136	136
Completed [2]	136	136
Not Completed	0	0
[1] One subject consented but was not randomized due to a miscommunication with the research pharmacy; [2] A second site (Houston VA) was added mid-study, and began enrolling 1/2018

Baseline Characteristics

Arm/Group Title		Longer (14 Day) Duration Antimicrobial Treatment	Shorter (7 Day) Duration Antimicrobial Treatment	Total
Arm/Group Description		14 days of ciprofloxacin or trimethoprim/sulfamethoxazole Longer therapy duration: 14 days of antimicrobial treatment	7 days of ciprofloxacin or trimethoprim/sulfamethoxazole, followed by 7 days of placebo Shorter therapy duration: 7 days of antimicrobial treatment	Total of all reporting groups
Overall Number of Baseline Participants		136	136	272
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	136 participants	136 participants	272 participants
		67.8 (11.6)	67.8 (11.6)	67.8 (11.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	136 participants	136 participants	272 participants
	Female	0 0.0%	0 0.0%	0 0.0%
	Male	136 100.0%	136 100.0%	272 100.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	136 participants	136 participants	272 participants
	Hispanic or Latino	8 5.9%	5 3.7%	13 4.8%
	Not Hispanic or Latino	126 92.6%	127 93.4%	253 93.0%
	Unknown or Not Reported	2 1.5%	4 2.9%	6 2.2%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	136 participants	136 participants	272 participants
	American Indian or Alaska Native	5 3.7%	1 0.7%	6 2.2%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	23 16.9%	26 19.1%	49 18.0%
	White	105 77.2%	107 78.7%	212 77.9%
	More than one race	2 1.5%	1 0.7%	3 1.1%
	Unknown or Not Reported	1 0.7%	1 0.7%	2 0.7%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	136 participants	136 participants	272 participants
		136 100.0%	136 100.0%	272 100.0%
Indwelling catheter use; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	136 participants	136 participants	272 participants
		8 5.9%	8 5.9%	16 5.9%
Intermittent catheter use; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	136 participants	136 participants	272 participants
		23 16.9%	24 17.6%	47 17.3%
Diabetes; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	136 participants	136 participants	272 participants
		60 44.1%	46 33.8%	106 39.0%
CKD; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	136 participants	136 participants	272 participants
		14 10.3%	8 5.9%	22 8.1%
Cerebrovascular accident; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	136 participants	136 participants	272 participants
		5 3.7%	13 9.6%	18 6.6%
Spinal cord injury; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	136 participants	136 participants	272 participants
		6 4.4%	5 3.7%	11 4.0%
HIV; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	136 participants	136 participants	272 participants
		2 1.5%	2 1.5%	4 1.5%
Prostatic hypertrophy; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	136 participants	136 participants	272 participants
		47 34.6%	56 41.2%	103 37.9%
Prostatitis; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	136 participants	136 participants	272 participants
		18 13.2%	16 11.8%	34 12.5%
Prostate Cancer; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	136 participants	136 participants	272 participants
		23 16.9%	21 15.4%	44 16.2%
Prior UTI; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	136 participants	136 participants	272 participants
		78 57.4%	84 61.8%	162 59.6%
Incontinence; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	136 participants	136 participants	272 participants
		52 38.2%	44 32.4%	96 35.3%
Urethral stricture; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	136 participants	136 participants	272 participants
		16 11.8%	17 12.5%	33 12.1%

Outcome Measures

1. Primary Outcome

Title	Resolution of UTI Symptoms 14 Days After Completing Active Antimicrobial Therapy
Description	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.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

Per-protocol analysis (including all subjects who took medication as directed, defined as at least 26 of 28 doses, missing no more than 2 consecutive doses)

Arm/Group Title	Longer (14 Day) Duration Antimicrobial Treatment	Shorter (7 Day) Duration Antimicrobial Treatment
Arm/Group Description:	14 days of ciprofloxacin or trimethoprim/sulfamethoxazole Longer therapy duration: 14 days of antimicrobial treatment	7 days of ciprofloxacin or trimethoprim/sulfamethoxazole, followed by 7 days of placebo Shorter therapy duration: 7 days of antimicrobial treatment
Overall Number of Participants Analyzed	123	131
Measure Type: Count of Participants; Unit of Measure: Participants
	111 90.2%	122 93.1%

2. Secondary Outcome

Title	Recurrent UTI Within 28 Days of Completing Active Study Medication
Description	New onset of symptomatic UTI within the 28 day follow-up period
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Longer (14 Day) Duration Antimicrobial Treatment	Shorter (7 Day) Duration Antimicrobial Treatment
Arm/Group Description:	14 days of ciprofloxacin or trimethoprim/sulfamethoxazole Longer therapy duration: 14 days of antimicrobial treatment	7 days of ciprofloxacin or trimethoprim/sulfamethoxazole, followed by 7 days of placebo Shorter therapy duration: 7 days of antimicrobial treatment
Overall Number of Participants Analyzed	123	131
Measure Type: Count of Participants; Unit of Measure: Participants
	15 12.2%	13 9.9%

3. Secondary Outcome

Title	Adverse Drug Event in the 28 Days After Completing Study Medication
Description	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
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Longer (14 Day) Duration Antimicrobial Treatment	Shorter (7 Day) Duration Antimicrobial Treatment
Arm/Group Description:	14 days of ciprofloxacin or trimethoprim/sulfamethoxazole Longer therapy duration: 14 days of antimicrobial treatment	7 days of ciprofloxacin or trimethoprim/sulfamethoxazole, followed by 7 days of placebo Shorter therapy duration: 7 days of antimicrobial treatment
Overall Number of Participants Analyzed	136	136
Measure Type: Count of Participants; Unit of Measure: Participants
	29 21.3%	26 19.1%

4. Secondary Outcome

Title	Intestinal Carriage of Antimicrobial-resistant Gram Negative Bacilli
Description	Intestinal carriage of antimicrobial-resistant Gram-negative bacilli after completing study medication, as compared to a baseline sample taken early in treatment.
Time Frame	7 days

Outcome Measure Data Not Reported

Adverse Events

Time Frame	28 days
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Longer (14 Day) Duration Antimicrobial Treatment		Shorter (7 Day) Duration Antimicrobial Treatment
Arm/Group Description	14 days of ciprofloxacin or trimethoprim/sulfamethoxazole Longer therapy duration: 14 days of antimicrobial treatment		7 days of ciprofloxacin or trimethoprim/sulfamethoxazole, followed by 7 days of placebo Shorter therapy duration: 7 days of antimicrobial treatment
All-Cause Mortality
	Longer (14 Day) Duration Antimicrobial Treatment		Shorter (7 Day) Duration Antimicrobial Treatment
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/136 (0.00%)		0/136 (0.00%)
Serious Adverse Events
	Longer (14 Day) Duration Antimicrobial Treatment		Shorter (7 Day) Duration Antimicrobial Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/136 (0.00%)		0/136 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Longer (14 Day) Duration Antimicrobial Treatment		Shorter (7 Day) Duration Antimicrobial Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/136 (24.26%)		28/136 (20.59%)
General disorders
Any adverse event † [1]	33/136 (24.26%)	51	28/136 (20.59%)	40
† Indicates events were collected by systematic assessment; [1] Adverse events assessed were: C difficile, nausea, vomiting, diarrhea, dizziness, headache, allergic reaction, thrush, muscle/joint aches, abnormal blood sugars, and changes in warfarin dosing. Subjects may have more than one adverse event.

Limitations and Caveats

Goal enrollment was 290; actual enrollment of 273 slightly reduces power to detect minimally clinically significant difference.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dimitri Drekonja, MD, MS
• Organization: Minneapolis VA Health Care System
• Phone: 612 467 4183
• EMail: dimitri.drekonja@va.gov

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT01994538
• Other Study ID Numbers: CLIN-008-13S; I01BX007080 ( Other Grant/Funding Number: VA Merit Review )
• First Submitted: November 19, 2013
• First Posted: November 25, 2013
• Results First Submitted: October 2, 2020
• Results First Posted: October 28, 2020
• Last Update Posted: October 28, 2020