NCT02384200

Brief Summary

When patients are going to have surgery to remove large kidney stones (percutaneous nephrolithotomy \[PCNL\]), it is not clear whether the patients benefit from a course of prophylactic preoperative oral antibiotics; currently both the use of prophylactic preoperative oral antibiotics and no prophylactic oral antibiotics are considered to be within standard-of-care. This study will randomize patients to preoperative prophylactic antibiotics or no antibiotics to determine if the use of preoperative prophylactic antibiotics decreases the postoperative risk of localized urinary tract infection (UTI) and/or systemic infection that started in the urinary tract (sepsis or urosepsis).

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
86

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started Mar 2015

Longer than P75 for phase_4

Geographic Reach
2 countries

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 22, 2015

Completed
7 days until next milestone

Study Start

First participant enrolled

March 1, 2015

Completed
9 days until next milestone

First Posted

Study publicly available on registry

March 10, 2015

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2017

Completed
2.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2019

Completed
3 months until next milestone

Results Posted

Study results publicly available

August 22, 2019

Completed
Last Updated

August 22, 2019

Status Verified

August 1, 2019

Enrollment Period

1.9 years

First QC Date

February 22, 2015

Results QC Date

July 14, 2019

Last Update Submit

August 7, 2019

Conditions

NephrolithiasisUrinary Tract Infections

Outcome Measures

Primary Outcomes (1)

  • Number of Participants That Developed Sepsis After Surgery

    "Sepsis" will be defined by the 2012 International Guidelines for Management of Severe Sepsis and Septic Shock where 2 or more of the following variables are present and temporally associated * Temp \> 38.3 C or \<36 C * Heart Rate \> 90/min (at least 12 hrs after surgery) * Respiratory Rate \> 20/min (at least 12 hrs after surgery) * Altered mental status: defined as lack of orientation to either name, place, or time/date. * Systolic Blood Pressure (SBP) \< 90 mmHg, Mean Arterial Pressure \< 70 mmHg, or SBP decrease \>40 mmHg in adults * WBC \>12000 or \< 4000

    Within 7 days following day of surgery

Secondary Outcomes (9)

  • Participants With Positive Renal Pelvic Urine Culture

    once at time of surgery, within 10 minutes of obtaining percutaneous access to the kidney

  • Participants With Positive Kidney Stone Culture

    once, within 6 hours of start of surgery

  • Positive Bladder Urine Culture

    once, within 30 minutes of start of surgery

  • Number of Participants With Postoperative Urinary Tract Infection (UTI)

    Within 12 weeks following day of surgery

  • Number of Participants With a Postoperative Fever Greater Than 38.3 Celsius

    within 7 days following day of surgery

  • +4 more secondary outcomes

Study Arms (2)

Antibiotic

EXPERIMENTAL

1 week course of preoperative nitrofurantoin monohydrate/macrocrystalline capsules 100 milligrams twice daily starting 1 week prior to planned kidney stone surgery (PCNL). In addition, each patient receives a a dose of ampicillin IV (2 g) and gentamicin IV (5 mg/kg) within 60 minutes of surgery start time. Patients with penicillin allergy will receive vancomycin IV (1 g) instead of ampicillin and patients with gentamicin/aminoglycoside allergy will receive ceftriaxone IV (2 g) instead of gentamicin.

Drug: nitrofurantoin monohydrate/macrocrystalline capsulesDrug: ampicillinDrug: gentamicinDrug: vancomycinDrug: ceftriaxone

No preoperative oral antibiotics

ACTIVE COMPARATOR

Each patient does receive a a dose of ampicillin IV (2 g) and gentamicin IV (5 mg/kg) within 60 minutes of surgery start time. Patients with penicillin allergy will receive vancomycin IV (1 g) instead of ampicillin and patients with gentamicin/aminoglycoside allergy will receive ceftriaxone IV (2 g) instead of gentamicin.

Drug: ampicillinDrug: gentamicinDrug: vancomycinDrug: ceftriaxone

Interventions

nitrofurantoin monohydrate/macrocrystalline capsulesDRUG

1 week course of preoperative nitrofurantoin monohydrate/macrocrystalline capsules 100 milligrams twice daily

Also known as: Macrobid
Antibiotic
ampicillinDRUG

IV (2 g)

AntibioticNo preoperative oral antibiotics
gentamicinDRUG

IV (5 mg/kg)

AntibioticNo preoperative oral antibiotics
vancomycinDRUG

IV (1 g)

AntibioticNo preoperative oral antibiotics
ceftriaxoneDRUG

IV (2 g)

AntibioticNo preoperative oral antibiotics

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Renal stone of any size for which PCNL is recommended

You may not qualify if:

  • eGFR \< 60 mL/min/1.73 m2
  • cirrhosis and/or hepatitis
  • Pregnancy
  • Positive preoperative urine culture within 2 weeks
  • History of temperature \>=38.3 C associated with nephrolithiasis or sepsis thought to be due to urinary source within 12 months prior to randomization
  • Current internalized ureteral stent, nephrostomy tube, or nephroureteral stent
  • Antibiotic use within 2 weeks prior to randomization
  • Severe hydronephrosis (defined by \> =2cm in largest dimension) preoperatively as judged on CT scan, abdominal X-ray, ultrasound, or fluoroscopy.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Mayo Clinic in Arizona

Phoenix, Arizona, 85054, United States

Location

UCSD Medical Center

San Diego, California, 92103, United States

Location

UCSF

San Francisco, California, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43212, United States

Location

Vanderbilt

Nashville, Tennessee, 37232-2765, United States

Location

University of British Columbia

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Related Publications (5)

  • de la Rosette J, Assimos D, Desai M, Gutierrez J, Lingeman J, Scarpa R, Tefekli A; CROES PCNL Study Group. The Clinical Research Office of the Endourological Society Percutaneous Nephrolithotomy Global Study: indications, complications, and outcomes in 5803 patients. J Endourol. 2011 Jan;25(1):11-7. doi: 10.1089/end.2010.0424.

    PMID: 21247286BACKGROUND

  • Korets R, Graversen JA, Kates M, Mues AC, Gupta M. Post-percutaneous nephrolithotomy systemic inflammatory response: a prospective analysis of preoperative urine, renal pelvic urine and stone cultures. J Urol. 2011 Nov;186(5):1899-903. doi: 10.1016/j.juro.2011.06.064. Epub 2011 Sep 23.

    PMID: 21944106BACKGROUND

  • Kumar S, Bag S, Ganesamoni R, Mandal AK, Taneja N, Singh SK. Risk factors for urosepsis following percutaneous nephrolithotomy: role of 1 week of nitrofurantoin in reducing the risk of urosepsis. Urol Res. 2012 Feb;40(1):79-86. doi: 10.1007/s00240-011-0386-6. Epub 2011 May 13.

    PMID: 21567157BACKGROUND

  • Wolf JS Jr, Bennett CJ, Dmochowski RR, Hollenbeck BK, Pearle MS, Schaeffer AJ; Urologic Surgery Antimicrobial Prophylaxis Best Practice Policy Panel. Best practice policy statement on urologic surgery antimicrobial prophylaxis. J Urol. 2008 Apr;179(4):1379-90. doi: 10.1016/j.juro.2008.01.068. Epub 2008 Feb 20.

    PMID: 18280509BACKGROUND

  • Bag S, Kumar S, Taneja N, Sharma V, Mandal AK, Singh SK. One week of nitrofurantoin before percutaneous nephrolithotomy significantly reduces upper tract infection and urosepsis: a prospective controlled study. Urology. 2011 Jan;77(1):45-9. doi: 10.1016/j.urology.2010.03.025. Epub 2010 Jun 8.

    PMID: 20570319BACKGROUND

MeSH Terms

Conditions

NephrolithiasisUrinary Tract Infections

Interventions

NitrofurantoinAmpicillinGentamicinsVancomycinCeftriaxone

Condition Hierarchy (Ancestors)

Kidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesUrolithiasisMale Urogenital DiseasesInfections

Intervention Hierarchy (Ancestors)

NitrofuransNitro CompoundsOrganic ChemicalsFuransHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPenicillin GPenicillinsbeta-LactamsLactamsAmidesSulfur CompoundsHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingAminoglycosidesGlycosidesCarbohydratesGlycopeptidesGlycoconjugatesPeptidesAmino Acids, Peptides, and ProteinsCefotaximeCephacetrileCephalosporinsThiazines

Results Point of Contact

Title
Paul Zupkas, Ph.D.
Organization
UCSD Medical Center
pzupkas@ucsd.edu
6195432628

Study Officials

  • Roger L Sur, MD

    University of California, San Diego

    PRINCIPAL INVESTIGATOR

  • Daniel L Miller, MD MPH

    University of California, San Diego

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Fellow

Study Record Dates

First Submitted

February 22, 2015

First Posted

March 10, 2015

Study Start

March 1, 2015

Primary Completion

February 1, 2017

Study Completion

June 1, 2019

Last Updated

August 22, 2019

Results First Posted

August 22, 2019

Record last verified: 2019-08

Data Sharing

IPD Sharing
Will not share

Locations

US(7)CA(1)