Antibiotic Prophylaxis for Transrectal Prostate Biopsy

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01659866
• Collaborator: (none)
• Enrollment: 563
• Location: 1
• Arms: 2
• Duration (Months): 48
• Patients Per Site Per Month: 11.7

Study Details

Study Description

Brief Summary

This study is being conducted in men scheduled to undergo transrectal ultrasound-guided prostate biopsy (TRUSP). Traditionally prior to prostate biopsy, an antibiotic, ciprofloxacin, has been given to men to prevent biopsy-related infections. In recent years as ciprofloxacin resistance has increased in the community, more and more men are becoming infected with ciprofloxacin-resistant bacteria after prostate biopsy. This study is being done to determine if obtaining rectal swab cultures and choosing antibiotics based on these culture results will result in fewer infectious complications than giving all men ciprofloxacin.

The investigators will compare 2 groups: men whose rectal swabs do not show ciprofloxacin-resistant bacteria will receive ciprofloxacin prior to biopsy, and men whose swabs do show ciprofloxacin-resistant bacteria will receive alternative antibiotics based on their culture results. Our hypothesis is that these 2 groups will have equal numbers of post-biopsy infectious complications and both groups will have fewer infectious complications than a historical group who received empiric ciprofloxacin without the benefit of rectal swab culture results.

Condition or Disease	Intervention/Treatment	Phase
Infection	Drug: Ciprofloxacin; Drug: trimethoprim-sulfamethoxazole; Drug: cefuroxime; Drug: ceftriaxone; Drug: gentamicin; Drug: amikacin; Drug: aztreonam; Drug: imipenem; Drug: ceftriaxone; Drug: gentamicin; Drug: amikacin; Drug: aztreonam; Drug: imipenem	Phase 4

Detailed Description

This study is a prospective, nonrandomized trial evaluating the efficacy of directed antimicrobial prophylaxis prior to transrectal ultrasound-guided prostate biopsy (TRUSP) compared with ciprofloxacin prophylaxis, the current standard of care. Northwestern University will be the lead site. After signing informed consent, study participants will complete a pre-biopsy questionnaire to record demographics and assess for known risk factors for infection and will have a rectal swab obtained. Patients whose swabs indicate colonization with ciprofloxacin-susceptible gram-negative bacteria (CS-GNB) will receive ciprofloxacin as pre-procedure prophylaxis and those whose swabs indicate colonization with ciprofloxacin-resistant gram-negative bacteria (CR-GNB) will receive pre-procedure antimicrobial prophylaxis based on study protocol.

All patients will be contacted by phone twice after their biopsies, at approximately 7 and 30 days, to detail post-procedure infectious complications including fever, urinary tract infection, bacteremia and sepsis. Subjects who experience infections will have additional information regarding the infectious complications and cost of therapy abstracted from their medical record. The TRUSP results will also be recorded. Bacterial isolates from the rectal swabs will be archived.

Study Design

• Study Type: Interventional
• Actual Enrollment: 563 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of Directed Antimicrobial Prophylaxis for Transrectal Ultrasound Guided Prostate Biopsy (TRUSP)
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Aug 1, 2015
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Other: Cipro-susceptible Patients with ciprofloxacin-susceptible bacteria on their rectal swab cultures will receive ciprofloxacin, the standard of care, as prophylaxis for their prostate biopsy	Drug: Ciprofloxacin; 500 mg orally 2 hours before prostate biopsy
Active Comparator: Cipro-resistant Patients with ciprofloxacin-resistant bacteria on their rectal swab will receive one of the following drugs: trimethoprim-sulfamethoxazole 1 double strength tablet orally 2 hours before the procedure and again 12 hours later cefuroxime 500 mg orally 2 hours before the procedure then again 12 hours later ceftriaxone 500 mg intramuscularly 2 hours before the procedure gentamicin 2mg/kg intramuscularly 2 hours before the procedure amikacin 5 mg/kg intramuscularly 2 hours before the procedure aztreonam 500 mg intramuscularly 2 hours before the procedure imipenem 500 mg intramuscularly 2 hours before the procedure ceftriaxone 2000 mg intravenously 1 hour before the procedure gentamicin 2 mg/kg intravenously 1 hour before the procedure amikacin 5mg/kg intravenously 1 hour before the procedure aztreonam 2000 mg intravenously 1 hour before the procedure imipenem 1000 mg intravenously 1 hour before the procedure	Drug: trimethoprim-sulfamethoxazole; 1 double strength tablet orally 2 hours before the procedure and again 12 hours later; Drug: cefuroxime; 500 mg orally 2 hours before the procedure then again 12 hours later; Drug: ceftriaxone; 500 mg intramuscularly 2 hours before the procedure; Drug: gentamicin; 2 mg/kg intramuscularly 2 hours before the procedure; Drug: amikacin; 5 mg/kg intramuscularly 2 hours before the procedure; Drug: aztreonam; 500 mg intramuscularly 2 hours before the procedure; Drug: imipenem; 500 mg intramuscularly 2 hours before the procedure; Drug: ceftriaxone; 2000 mg intravenously 1 hour before the procedure; Drug: gentamicin; 2 mg/kg intravenously 1 hour before the procedure; Drug: amikacin; 5 mg/kg intravenously 1 hour before the procedure; Drug: aztreonam; 2000 mg intravenously 1 hour before the procedure; Drug: imipenem; 1000 mg intravenously 1 hour before the procedure

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Post-biopsy Infection. [30 days post-biopsy]

   To measure and compare the rates of infection following TRUSP in subjects with and without CR-GNB. This measure is number of participants with post-biopsy infection.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 90 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Ability and willingness to provide written informed consent.

• All individuals who will undergo TRUSP as part of their standard of care are eligible for study.

Exclusion Criteria:

• Men under 30 years of age

• Individuals whose rectal swab indicates that they harbor CS-GNB who cannot receive ciprofloxacin as pre-procedure prophylaxis for any reason

• Individuals whose rectal swab indicates that they harbor CR-GNB who cannot abide by the antimicrobial prophylaxis guidelines outlined in the study protocol for any reason

• Individuals who do not wish to complete the pre-procedure risk factor questionnaire or the two post-procedure phone questionnaires to assess for infectious complications

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University Department of Urology	Chicago	Illinois	United States	60611

Sponsors and Collaborators

• Northwestern University

Investigators

• Principal Investigator: Anthony J Schaeffer, MD, Northwestern University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Anthony Schaeffer, Herman L. Kretschmer Professor and Chair, Department of Urology, Northwestern University
• ClinicalTrials.gov Identifier: NCT01659866
• Other Study ID Numbers: STU00059558; EAM-237
• First Posted: Aug 8, 2012
• Last Update Posted: Jun 25, 2019
• Last Verified: Sep 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Anthony Schaeffer, Herman L. Kretschmer Professor and Chair, Department of Urology, Northwestern University: Infection; Antibiotic resistance; Prostate biopsy
• Additional relevant MeSH terms: Infections; Ciprofloxacin; Gentamicins; Ceftriaxone; Imipenem; Amikacin; Cefuroxime; Trimethoprim, Sulfamethoxazole Drug Combination; Aztreonam; Trimethoprim; Sulfamethoxazole

Study Results

Participant Flow

Pre-assignment Detail	563 patients consented and of these, 53 were excluded as follows: 16 patients had issues with informed consent, 20 received antimicrobials off protocol, 16 did not undergo TRUSP and 1 was lost to follow up. Thus 510 patients underwent swabs; 430 had CS isolates while 80 had CR isolates. All 510 patients completed the study.

Arm/Group Title	Cipro-susceptible	Cipro-resistant
Arm/Group Description	Patients with ciprofloxacin-susceptible bacteria on their rectal swab cultures will receive ciprofloxacin, the standard of care, as prophylaxis for their prostate biopsy Ciprofloxacin: 500 mg orally 2 hours before prostate biopsy	Patients with ciprofloxacin-resistant bacteria on their rectal swab will receive one of the following drugs: trimethoprim-sulfamethoxazole 1 double strength tablet orally 2 hours before the procedure and again 12 hours later cefuroxime 500 mg orally 2 hours before the procedure then again 12 hours later ceftriaxone 500 mg intramuscularly 2 hours before the procedure gentamicin 2mg/kg intramuscularly 2 hours before the procedure amikacin 5 mg/kg intramuscularly 2 hours before the procedure aztreonam 500 mg intramuscularly 2 hours before the procedure imipenem 500 mg intramuscularly 2 hours before the procedure ceftriaxone 2000 mg intravenously 1 hour before the procedure gentamicin 2 mg/kg intravenously 1 hour before the procedure amikacin 5mg/kg intravenously 1 hour before the procedure aztreonam 2000 mg intravenously 1 hour before the procedure imipenem 1000 mg intravenously 1 hour before the procedure
Period Title: Overall Study
STARTED	430	80
COMPLETED	430	80
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Cipro-susceptible	Cipro-resistant	Total
Arm/Group Description	Patients with ciprofloxacin-susceptible bacteria on their rectal swab cultures will receive ciprofloxacin, the standard of care, as prophylaxis for their prostate biopsy Ciprofloxacin: 500 mg orally 2 hours before prostate biopsy	Patients with ciprofloxacin-resistant bacteria on their rectal swab will receive one of the following drugs: trimethoprim-sulfamethoxazole 1 double strength tablet orally 2 hours before the procedure and again 12 hours later cefuroxime 500 mg orally 2 hours before the procedure then again 12 hours later ceftriaxone 500 mg intramuscularly 2 hours before the procedure gentamicin 2mg/kg intramuscularly 2 hours before the procedure amikacin 5 mg/kg intramuscularly 2 hours before the procedure aztreonam 500 mg intramuscularly 2 hours before the procedure imipenem 500 mg intramuscularly 2 hours before the procedure ceftriaxone 2000 mg intravenously 1 hour before the procedure gentamicin 2 mg/kg intravenously 1 hour before the procedure amikacin 5mg/kg intravenously 1 hour before the procedure aztreonam 2000 mg intravenously 1 hour before the procedure imipenem 1000 mg intravenously 1 hour before the procedure	Total of all reporting groups
Overall Participants	430	80	510
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.7 (9.1)	61.6 (7.6)	62.4 (8.8)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	430 100%	80 100%	510 100%
Region of Enrollment (participants) [Number]
United States	430 100%	80 100%	510 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Post-biopsy Infection.
Description	To measure and compare the rates of infection following TRUSP in subjects with and without CR-GNB. This measure is number of participants with post-biopsy infection.
Time Frame	30 days post-biopsy

Outcome Measure Data

Analysis Population Description

Of the 563 patients who signed consent, 53 were excluded; thus, 510 patients participated in the study. Of these 510, 430 harbored ciprofloxacin-susceptible flora and 80 harbored ciprofloxacin-resistant flora.

Arm/Group Title	Cipro-susceptible	Cipro-resistant
Arm/Group Description	Patients with ciprofloxacin-susceptible bacteria on their rectal swab cultures will receive ciprofloxacin, the standard of care, as prophylaxis for their prostate biopsy Ciprofloxacin: 500 mg orally 2 hours before prostate biopsy	Patients with ciprofloxacin-resistant bacteria on their rectal swab will receive one of the following drugs: trimethoprim-sulfamethoxazole 1 double strength tablet orally 2 hours before the procedure and again 12 hours later cefuroxime 500 mg orally 2 hours before the procedure then again 12 hours later ceftriaxone 500 mg intramuscularly 2 hours before the procedure gentamicin 2mg/kg intramuscularly 2 hours before the procedure amikacin 5 mg/kg intramuscularly 2 hours before the procedure aztreonam 500 mg intramuscularly 2 hours before the procedure imipenem 500 mg intramuscularly 2 hours before the procedure ceftriaxone 2000 mg intravenously 1 hour before the procedure gentamicin 2 mg/kg intravenously 1 hour before the procedure amikacin 5mg/kg intravenously 1 hour before the procedure aztreonam 2000 mg intravenously 1 hour before the procedure imipenem 1000 mg intravenously 1 hour before the procedure
Measure Participants	430	80
Number [participants]	6 1.4%	3 3.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cipro-susceptible, Cipro-resistant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	30 days
Arm/Group Title	Cipro-susceptible		Cipro-resistant
Arm/Group Description	Patients with ciprofloxacin-susceptible bacteria on their rectal swab cultures will receive ciprofloxacin, the standard of care, as prophylaxis for their prostate biopsy Ciprofloxacin: 500 mg orally 2 hours before prostate biopsy		Patients with ciprofloxacin-resistant bacteria on their rectal swab will receive one of the following drugs: trimethoprim-sulfamethoxazole 1 double strength tablet orally 2 hours before the procedure and again 12 hours later cefuroxime 500 mg orally 2 hours before the procedure then again 12 hours later ceftriaxone 500 mg intramuscularly 2 hours before the procedure gentamicin 2mg/kg intramuscularly 2 hours before the procedure amikacin 5 mg/kg intramuscularly 2 hours before the procedure aztreonam 500 mg intramuscularly 2 hours before the procedure imipenem 500 mg intramuscularly 2 hours before the procedure ceftriaxone 2000 mg intravenously 1 hour before the procedure gentamicin 2 mg/kg intravenously 1 hour before the procedure amikacin 5mg/kg intravenously 1 hour before the procedure aztreonam 2000 mg intravenously 1 hour before the procedure imipenem 1000 mg intravenously 1 hour before the procedure
All Cause Mortality
	Cipro-susceptible		Cipro-resistant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/430 (0%)		0/80 (0%)
Serious Adverse Events
	Cipro-susceptible		Cipro-resistant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/430 (0%)		0/80 (0%)
Other (Not Including Serious) Adverse Events
	Cipro-susceptible		Cipro-resistant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/430 (0%)		0/80 (0%)

Limitations/Caveats

Did not reach recruiting targets due to fewer prostate biopsies being performed than originally estimated in the study period.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.