- To assess the effectiveness of rectal culture-guided antimicrobial prophylaxis for transrectal prostate biopsy (random ultrasound-guided, targeted MRI-guided or targeted MRI-ultrasound fusion guided) on infectious complications. - To compare the…
ID
Source
Brief title
Condition
- Other condition
- Bacterial infectious disorders
Synonym
Health condition
screening op prostaatcarcinoom (d.m.v. prostaatbiopsie)
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Any registered clinical infectious complication (urinary tract infection (UTI),
pyelonephritis, sepsis, fever, acute prostatitis, acute epididymitis) within 7
days after transrectal prostate biopsy.
* UTI is defined as pyuria (>5 leucocytes per high-powered field) and
bacteriuria (*10^3 colony-forming units/ml) with symptoms of dysuria, urgency,
frequency or hematuria.
* pyelonephritis is defined as pyuria and bacteriuria with symptoms of fever,
flank pain, nausea or vomiting.
* fever is defined as a temperature *38.0°C.
* sepsis is defined as suspected infection plus at least two of the following
criteria (qSOFA score): low blood pressure (SBP*100 mmHg), high respiratory
rate (*22 breaths per min), or altered mentation (Glasgow coma scale <15).
* severe sepsis or septic shock is defined as sepsis plus organ dysfunction or
with persisting hypotension requiring vasopressors to maintain MAP *65 mmHg and
to have a serum lactate level <2 mmol/L despite adequate volume resuscitation.
* acute prostatitis is defined as fever, bacteriuria and/or pyuria, and a
painful prostate.
* acute epididymitis is defined as the presence of a swollen, red or warm
scrotum and pain for which antibiotics are prescribed.
Secondary outcome
1. Cost of care 30 days after transrectal prostate biopsy to determine and
compare overall costs of care among the intervention- and the control group.
2. Positive microbiological urine or blood culture results within 7 and 30 days
after transrectal prostate biopsy.
3. Clinical infectious complications (as for primary endpoint) within 30 days
after transrectal prostate biopsy.
Exploratory:
1. Hospitalization, including ICU admission and length of admission, within 30
days after transrectal prostate biopsy.
2. Overall mortality within 30 days after transrectal prostate biopsy.
3. Side effects and toxicity of used antibiotics within 30 days after
transrectal prostate biopsy.
4. Prevalence of ciprofloxacin resistant GNB in local rectal flora, assessed
through microbiological rectal swab cultures.
5. Overall antibiotic use within 30 days after transrectal prostate biopsy.
6. The relation between antibiotic resistance in the fecal carriage and other
determinants of infection after transrectal prostate biopsy.
7. Experiences of patients and healthcare professionals regarding barriers and
facilitators (determinants) that influence the performance of the
culture-guided approach in daily clinical practice.
Background summary
Transrectal ultrasound guided prostate biopsy (TRUS-PB) is a well established
procedure to obtain tissue for the histological diagnosis of prostate cancer.
In The Netherlands, TRUS-PB is performed in approximately 40.000 patients
annually. During TRUS-PB, a spring-loaded device is used to collect multiple
core biopsies, sampling tissue systematically from both sides of the gland. A
variety of infectious complications may occur following transrectal prostate
biopsy, ranging from asymptomatic bacteriuria or urinary tract infection (UTI)
to prostatitis, bacteremia, and severe sepsis. Although no studies have clearly
defined the pathophysiology of TRUS-PB related infectious complications, the
cause appears to be direct inoculation of bacteria from the rectal mucosa by
the biopsy needle into the prostate, blood vessels, or urinary tract.
Several classes of antibiotics are proven effective for prophylaxis during
TRUS-PB, reducing infectious complications to less than 1% in case of
susceptible rectal flora. Ciprofloxacin has been best studied and is
recommended as first choice prophylaxis in American, European en Dutch urology
guidelines, although no clear recommendations are made on the duration of
prophylaxis. In the Netherlands, therefore, various prophylactic ciprofloxacin
schedules are used, of which 2 to 3 days regimens are most common. Prolonged
duration of prophylaxis in TRUS-PB is not proven to be more effective than a
1-day regimen, but it is more likely to select more fluoroquinolone (FQ)
resistance
Due to increasing FQ resistance in gram negative bacilli (GNB) (currently more
than 20% in E. coli), a significant increase up to 6% in infectious
complications after TRUS-PB procedures was recently noticed. Antibiotic
treatment of these infections and hospitalization may account for increased
health care associated costs and will contribute to the further development of
antibiotic resistance.
Directed antibiotic prophylaxis based on resistance data of individual rectal
cultures may be an effective strategy to overcome the problem of increasing
fluoroquinolone (FQ) resistance and reduce infectious complications after
transrectal prostate biopsy. Previous studies already showed promising results
but had retrospective designs, did not use control groups, used unclear
screenings techniques or were underpowered. In addition, expensive and
time-consuming bacterial culture methods were performed. Moreover, the majority
of these studies used intravenous antibiotics in case of FQ resistance. Oral
alternatives to FQ, if available, are preferred over intravenous prophylaxis,
because they are cheaper and more comfortable for the patient.
In the Radboudumc, MRI-guided or MRI-ultrasound fusion guided prostate biopsies
are performed in almost all patients instead of TRUS-PB. MRI of the prostate is
capable of detecting clinically relevant prostate cancer. Therefore patients
with a normal MRI of the prostate may not need to undergo transrectal prostate
biopsy. Moreover, MRI-guided or MRI-ultrasound fusion guided lesion targeting,
allows urologist to progress from blind, systematic biopsies with 12 core
samples to more accurate targeted biopsies with only 2 till 4 core samples.
Because less core samples are taken with these techniques, the amount of
infectious complications after MRI-guided or MRI-ultrasound fusion guided
prostate biopsies might be reduced compared to TRUS-PB. However, there is no
literature available on this subject.
Study objective
- To assess the effectiveness of rectal culture-guided antimicrobial
prophylaxis for transrectal prostate biopsy (random ultrasound-guided, targeted
MRI-guided or targeted MRI-ultrasound fusion guided) on infectious
complications.
- To compare the cost-effectiveness of empirical antimicrobial prophylaxis
(ciprofloxacin) to rectal culture-guided antimicrobial prophylaxis for
transrectal prostate biopsy.
- To assess experiences of patients and professionals regarding barriers and
facilitators (determinants) that influence the performance of the
culture-guided approach in daily clinical practice.
With a culture-guided antibiotic prophylaxis strategy we aim to contribute to
the control of antibiotic resistance by reducing infectious complications (less
use of therapeutic antibiotics), prescription of prophylaxis based on rectal
microbiome data and reducing duration of antibiotic prophylaxis to 24 hours
(except for pivmecillinam/augmentin prophylaxis). Moreover, we will be able to
compare the difference of infectious complications after random transrectal
ultrasound-guided, targeted MRI and MRI-ultrasound fusion guided prostate
biopsy.
Study design
Prospective, randomized, open-label, comparative, multi-center trial with two
study arms (intervention group and control group).
Intervention
Patients will be randomized into two groups of 809 patients each with
stratification for study site and type of prostate biopsy (random
ultrasound-guided, targeted MRI-guided, targeted MRI-ultrasound fusion guided):
Control group: empirical prophylaxis strategy (standard of care)
(ciprofloxacin 500 mg orally 2 hours before and 12 hours after the procedure).
Intervention group: culture-guided oral antibiotic prophylaxis strategy.
Men whose rectal swabs do not show ciprofloxacin-resistant bacteria (estimated
at 75-80%) will receive ciprofloxacin prophylaxis (similar to the control
group), and men whose swabs do show ciprofloxacin-resistant bacteria will
receive alternative oral antibiotics based on the culture results (in the
following order):
* trimethoprim/sulfamethoxazole (SXT) 960 mg orally 2 hours before the
procedure and again 12 hours later, or
* fosfomycin 3 g orally 2 hours before the procedure, or
* pivmecillinam/amoxicilline/clavulaanzuur respectively 400 mg and 500/125 mg 2
hours before biopsy, followed by 2 days with three divided doses each day after
biopsy
Study burden and risks
At three moments during the study period patients have to fill in a few
questionnaires:
- Baseline (approximately 7 days prior to prostate biopsy): questionnaire about
demographic parameters, use of medication (including antibiotics), medical
history, allergies and other parameters which might intervene with the study
outcome, EQ-5D-5L (to assess health status), iMTA PCQ (to assess productivity
loss).
- At approximately 7 days and 30 days after prostate biopsy: questionnaire
about the study measurements, EQ-5D-5L, iMTA PCQ.
At two moments during the study period a rectal swab is performed (at home by
self-sampling approximately 14 days prior to prostate biopsy and immediately
before prostate biopsy by the urologist). Utility of a rectum swab culture is a
minimally invasive method to provide information on patients' rectal flora.
At baseline, some patients (phase 1) will be approached for an in-depth
interview (approximately 5-10 patients per center, for approximately 1 hour per
patient) as part of an analysis of determinants that influence the performance
of the culture-guided approach in daily clinical practice. Interviews will take
place at a with the patient agreed upon moment and location. Based upon these
results, a questionnaire will be developed to assess barriers and facilitators
experienced. Thereafter (phase 2), approximately 50-100 patients per center
will be asked to fill in an extra questionnaire at baseline (approximately 15
minutes).
According to the laws and regulations associated with research with a medicinal
product, the study medication must be provided from the Clinical Trial Units of
the hospital pharmacies of the participating centers. Therefore, participants
can not obtain the antimicrobial prophylaxis at their home pharmacy.
Participants will be offered two choices: to obtain the antimicrobial
prophylaxis in the days before prostate biopsy at the hospital pharmacy
(consequence: extra trip to the hospital) or to be present in the hospital two
hours prior to prostate biopsy and then obtain the antimicrobial prophylaxis at
the hospital pharmacy (and take the antimicrobial prophylaxis immediately). No
extra other (study-related) hospital visits are required.
Risks associated with participation:
The risks associated with participation in the study are negligible. Utility of
a rectum swab culture is a minimally invasive and safe method to provide
information on a participant*s rectal flora. It is already routine procedure
for patients, admitted to Dutch hospitals, that are at risk for carriage of
multidrug resistant bacteria (HRMO screening or methicillin-resistant
Staphylococcus aureus (MRSA).
The alternative antibiotics which may be prescribed in case of FQ resistance
are all registered in the Netherlands and good, logical alternatives as
antimicrobial prophylactic around prostate biopsy. We do not expect additional
risks compared to the use of the standard antibiotic prophylaxis with
ciprofloxacin and besides already registered adverse effects. In addition, it
should be mentioned that it concerns antibiotic prophylaxis, which means that
the antibiotics are used only for a short period (mostly only for up to 24
hours).
Benefit:
We expect that the intervention group (with rectal swab culture-guided
antimicrobial prophylaxis) will have a lower risk of post-biopsy infectious
complications compared to the control group (estimated at respectively 0.8% and
2.6%).
Geert Grooteplein zuid 10
Nijmegen 6525GA
NL
Geert Grooteplein zuid 10
Nijmegen 6525GA
NL
Listed location countries
Age
Inclusion criteria
- Subject undergoes a transrectal prostate biopsy as part of the standard care
in one of the participating (study) centers (because of suspicion of prostate
cancer).
- Subject is able and willing to sign the Informed Consent Form.
Exclusion criteria
- Inability to receive ciprofloxacin prophylaxis for any reason (e.g.
documented history of sensitivity to medicinal products or excipients similar
to those found in the antibiotic prophylaxis, relevant history or presence of
cardiovascular disorders (specific relevant QTc time prolongation), relevant
drug interaction).
- Inability to receive either co-trimoxazole, fosfomycin and
pivmecillinam/augmentin prophylaxis for any reason (e.g. documented history of
sensitivity to medicinal products or excipients similar to those found in the
antibiotic prophylaxis, relevant drug interaction).
- Inability to understand the nature of the trial and the procedures required.
- Individuals with an urinary tract infection or acute prostatitis within 14
days prior to transrectal prostate biopsy.
- Individuals who received antibiotics within 14 days prior to transrectal
prostate biopsy.
- Individuals who fail to send a rectum swab to the microbiology laboratory.
- Individuals whose rectal swab shows no growth on a Colombia blood agar (CBP)
(growth control)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-002938-23-NL |
| ClinicalTrials.gov | NCT03228108 |
| CCMO | NL63566.091.17 |