Clinical trial NCT02650518: Controlling Antimicrobial Use Through Reducing Unnecessary Treatment of Catheter Associated Urinary Tract Infections
Official title: Controlling Antimicrobial Use Through Reducing Unnecessary Treatment of Catheter Associated Urinary Tract Infections (CARCUTI)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Catheter-Related Infections
Keywords: Catheter-Associated Urinary Tract Infections
Antimicrobial Stewardship
Short-Course Antimicrobials
Lead sponsor: National University Hospital, Singapore
Sponsor class: OTHER
Collaborators: name: Tan Tock Seng Hospital
name: Singapore General Hospital
name: National University of Singapore
First posted: 2016-01-08
Enrollment: 500
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Hypothesis: A short course (3-5 days) of antibiotic therapy (experimental arm) is as safe and effective as a long course of antibiotic therapy for the treatment of catheter-associated urinary tract infections.


Eligibility criteria: Inclusion Criteria:

1. Inpatients ≥ 21 years old.
2. Presence of indwelling urinary catheter at the time of urine culture for ≥2days.
3. Fever \>38°C.
4. A urine specimen sent to the hospital microbiological laboratory for culture.
5. An antibiotic order for presumed symptomatic catheter associated urinary tract infection.

Exclusion Criteria:

1. Persistent fever \>38°C for more than 24 hours, or any fever \>38.9°C.
2. Haemodynamic instability, defined as:

   * Requirement for intravenous vasopressor agents
   * Systolic blood pressure \<90 mmHg
   * Acute hypotensive event with drop in systolic blood pressure of \>30 mmHg or diastolic blood pressure of \>20 mmHg
3. The following laboratory values within the previous 48 hours (if available):

   * White blood cell count\>15 or \<4 x10\^9/L.
   * Procalcitonin\>0.25ug/mL
   * C Reactive Protein \>100mg/mL
   * An increase in the serum creatinine of more than 50% from baseline
4. New requirement for oxygen supplement.
5. Current admission to a high dependency unit or ICU.
6. Radiological evidence of an upper urinary tract infection
7. Flank pain or tenderness, suggesting an upper urinary tract infection
8. Urologic surgical procedure within the previous 72 hours
9. Known structural genitourinary abnormalities including:

   * Nephrostomy tubes
   * Tumours of the urinary tract
   * Ureteric stenting
   * Ureteric strictures
   * Urolithiasis
10. Bloodstream or other significant infection suspected at any site other than the catheterized urinary tract.
11. Received antibiotics for more than 48 hours prior to randomization.
12. Positive urinary culture with organism resistant to all the investigational antibiotics in the week prior to randomisation.
13. Hypersensitivity to ciprofloxacin, cotrimoxazole and amoxicillin-clavulanate.
14. Pregnancy.

Primary outcomes:
measure: Resolution
timeFrame: Day 14 post-randomisation
Secondary outcomes:
measure: Short-Term Resolution
timeFrame: day 3 and day 7 post-randomisation
measure: Recurrence of fever or symptoms
timeFrame: 7, 14 and 30 days post randomization
measure: Haemodynamic instability
timeFrame: day 14 post randomization
measure: Admission to high dependency or intensive care units
timeFrame: 14 days post-randomization
measure: Length of hospitalization
timeFrame: 30 days post-randomization
measure: Re-admission
timeFrame: Day 30 post-randomization
measure: Secondary Infections
timeFrame: 3 months post-randomization
measure: Recurrent Urinary Tract Infections
timeFrame: 3 months and 1 year post-randomization
measure: Urologic surgery or procedure
timeFrame: 1 year post-randomization
measure: Antimicrobial use and duration
timeFrame: 1 month post-randomization
measure: Colonization or infection by antibiotic-resistant organisms
timeFrame: 30 days post-randomization
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
Study officials:
affiliation: National University Hospital, Singapore
name: Paul A Tambyah, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Edwards JR, Peterson KD, Andrus ML, Tolson JS, Goulding JS, Dudeck MA, Mincey RB, Pollock DA, Horan TC; NHSN Facilities. National Healthcare Safety Network (NHSN) Report, data summary for 2006, issued June 2007. Am J Infect Control. 2007 Jun;35(5):290-301. doi: 10.1016/j.ajic.2007.04.001. No abstract available.
citation: Schaberg DR, Weinstein RA, Stamm WE. Epidemics of nosocomial urinary tract infection caused by multiply resistant gram-negative bacilli: epidemiology and control. J Infect Dis. 1976 Mar;133(3):363-6. doi: 10.1093/infdis/133.3.363. No abstract available.
citation: Milan PB, Ivan IM. Catheter-associated and nosocomial urinary tract infections: antibiotic resistance and influence on commonly used antimicrobial therapy. Int Urol Nephrol. 2009;41(3):461-4. doi: 10.1007/s11255-008-9468-y. Epub 2008 Sep 12.
citation: Tambyah PA, Knasinski V, Maki DG. The direct costs of nosocomial catheter-associated urinary tract infection in the era of managed care. Infect Control Hosp Epidemiol. 2002 Jan;23(1):27-31. doi: 10.1086/501964.
citation: Wald HL, Ma A, Bratzler DW, Kramer AM. Indwelling urinary catheter use in the postoperative period: analysis of the national surgical infection prevention project data. Arch Surg. 2008 Jun;143(6):551-7. doi: 10.1001/archsurg.143.6.551.
citation: Hooton TM, Bradley SF, Cardenas DD, Colgan R, Geerlings SE, Rice JC, Saint S, Schaeffer AJ, Tambayh PA, Tenke P, Nicolle LE; Infectious Diseases Society of America. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010 Mar 1;50(5):625-63. doi: 10.1086/650482.
citation: Ng E, Earnest A, Lye DC, Ling ML, Ding Y, Hsu LY. The excess financial burden of multidrug resistance in severe gram-negative infections in Singaporean hospitals. Ann Acad Med Singap. 2012 May;41(5):189-93.
citation: Harding GK, Nicolle LE, Ronald AR, Preiksaitis JK, Forward KR, Low DE, Cheang M. How long should catheter-acquired urinary tract infection in women be treated? A randomized controlled study. Ann Intern Med. 1991 May 1;114(9):713-9. doi: 10.7326/0003-4819-114-9-713.
citation: Peterson J, Kaul S, Khashab M, Fisher AC, Kahn JB. A double-blind, randomized comparison of levofloxacin 750 mg once-daily for five days with ciprofloxacin 400/500 mg twice-daily for 10 days for the treatment of complicated urinary tract infections and acute pyelonephritis. Urology. 2008 Jan;71(1):17-22. doi: 10.1016/j.urology.2007.09.002.
citation: Dow G, Rao P, Harding G, Brunka J, Kennedy J, Alfa M, Nicolle LE. A prospective, randomized trial of 3 or 14 days of ciprofloxacin treatment for acute urinary tract infection in patients with spinal cord injury. Clin Infect Dis. 2004 Sep 1;39(5):658-64. doi: 10.1086/423000. Epub 2004 Aug 13.
citation: Raz R, Schiller D, Nicolle LE. Chronic indwelling catheter replacement before antimicrobial therapy for symptomatic urinary tract infection. J Urol. 2000 Oct;164(4):1254-8.
citation: Darouiche RO, Al Mohajer M, Siddiq DM, Minard CG. Short versus long course of antibiotics for catheter-associated urinary tract infections in patients with spinal cord injury: a randomized controlled noninferiority trial. Arch Phys Med Rehabil. 2014 Feb;95(2):290-6. doi: 10.1016/j.apmr.2013.09.003. Epub 2013 Sep 11.
citation: Singh N, Rogers P, Atwood CW, Wagener MM, Yu VL. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):505-11. doi: 10.1164/ajrccm.162.2.9909095.
citation: Hamasuna R, Takahashi S, Yamamoto S, Arakawa S, Yanaihara H, Ishikawa S, Matsumoto T. Guideline for the prevention of health care-associated infection in urological practice in Japan. Int J Urol. 2011 Jul;18(7):495-502. doi: 10.1111/j.1442-2042.2011.02769.x. Epub 2011 May 16.
citation: Tambyah PA, Maki DG. Catheter-associated urinary tract infection is rarely symptomatic: a prospective study of 1,497 catheterized patients. Arch Intern Med. 2000 Mar 13;160(5):678-82. doi: 10.1001/archinte.160.5.678.
citation: Corey GR, Stryjewski ME. New rules for clinical trials of patients with acute bacterial skin and skin-structure infections: do not let the perfect be the enemy of the good. Clin Infect Dis. 2011 Jun;52 Suppl 7:S469-76. doi: 10.1093/cid/cir162.
citation: Blackwelder WC. "Proving the null hypothesis" in clinical trials. Control Clin Trials. 1982 Dec;3(4):345-53. doi: 10.1016/0197-2456(82)90024-1.
citation: Scott IA. Non-inferiority trials: determining whether alternative treatments are good enough. Med J Aust. 2009 Mar 16;190(6):326-30. doi: 10.5694/j.1326-5377.2009.tb02425.x.