Trial Outcomes & Findings for A Randomized Trial of Preoperative Prophylactic Antibiotics Prior to Kidney Stone Surgery (Percutaneous Nephrolithotomy [PCNL]) (NCT NCT02384200)

Results Overview

"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

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

86 participants

Primary outcome timeframe

Within 7 days following day of surgery

Results posted on

2019-08-22

Participant Flow

Participant milestones

Participant milestones
Measure	Antibiotic 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. nitrofurantoin monohydrate/macrocrystalline capsules: 1 week course of preoperative nitrofurantoin monohydrate/macrocrystalline capsules 100 milligrams twice daily ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)	No Preoperative Oral Antibiotics 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. ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)
Overall Study STARTED	43	43
Overall Study COMPLETED	43	43
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Antibiotic n=43 Participants 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. nitrofurantoin monohydrate/macrocrystalline capsules: 1 week course of preoperative nitrofurantoin monohydrate/macrocrystalline capsules 100 milligrams twice daily ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)	No Preoperative Oral Antibiotics n=43 Participants 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. ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)	Total n=86 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=43 Participants	0 Participants n=43 Participants	0 Participants n=86 Participants
Age, Categorical Between 18 and 65 years	43 Participants n=43 Participants	43 Participants n=43 Participants	86 Participants n=86 Participants
Age, Categorical >=65 years	0 Participants n=43 Participants	0 Participants n=43 Participants	0 Participants n=86 Participants
Sex: Female, Male Female	16 Participants n=43 Participants	17 Participants n=43 Participants	33 Participants n=86 Participants
Sex: Female, Male Male	27 Participants n=43 Participants	26 Participants n=43 Participants	53 Participants n=86 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Canada	4 participants n=43 Participants	4 participants n=43 Participants	8 participants n=86 Participants
Region of Enrollment United States	39 participants n=43 Participants	39 participants n=43 Participants	78 participants n=86 Participants

PRIMARY outcome

Timeframe: Within 7 days following day of 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

Outcome measures

Outcome measures
Measure	No Preoperative Oral Antibiotics n=43 Participants 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. ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)	Antibiotic n=43 Participants 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. nitrofurantoin monohydrate/macrocrystalline capsules: 1 week course of preoperative nitrofurantoin monohydrate/macrocrystalline capsules 100 milligrams twice daily ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)
Number of Participants That Developed Sepsis After Surgery	6 Participants	5 Participants

SECONDARY outcome

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

percutaneously taken renal pelvic urine culture

Outcome measures

Outcome measures
Measure	No Preoperative Oral Antibiotics n=43 Participants 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. ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)	Antibiotic n=43 Participants 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. nitrofurantoin monohydrate/macrocrystalline capsules: 1 week course of preoperative nitrofurantoin monohydrate/macrocrystalline capsules 100 milligrams twice daily ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)
Participants With Positive Renal Pelvic Urine Culture	1 Participants	1 Participants

SECONDARY outcome

Timeframe: once, within 6 hours of start of surgery

Kidney stone sent for culture

Outcome measures

Outcome measures
Measure	No Preoperative Oral Antibiotics n=43 Participants 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. ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)	Antibiotic n=43 Participants 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. nitrofurantoin monohydrate/macrocrystalline capsules: 1 week course of preoperative nitrofurantoin monohydrate/macrocrystalline capsules 100 milligrams twice daily ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)
Participants With Positive Kidney Stone Culture	4 Participants	4 Participants

SECONDARY outcome

Timeframe: once, within 30 minutes of start of surgery

bladder urine culture taken during kidney stone surgery

Outcome measures

Outcome measures
Measure	No Preoperative Oral Antibiotics n=43 Participants 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. ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)	Antibiotic n=43 Participants 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. nitrofurantoin monohydrate/macrocrystalline capsules: 1 week course of preoperative nitrofurantoin monohydrate/macrocrystalline capsules 100 milligrams twice daily ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)
Positive Bladder Urine Culture	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Within 12 weeks following day of surgery

symptomatic urinary tract infection

Outcome measures

Outcome measures
Measure	No Preoperative Oral Antibiotics n=43 Participants 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. ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)	Antibiotic n=43 Participants 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. nitrofurantoin monohydrate/macrocrystalline capsules: 1 week course of preoperative nitrofurantoin monohydrate/macrocrystalline capsules 100 milligrams twice daily ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)
Number of Participants With Postoperative Urinary Tract Infection (UTI)	0 Participants	2 Participants

SECONDARY outcome

Timeframe: within 7 days following day of surgery

Body temperature \>= 38.3 degrees Celsius

Outcome measures

Outcome measures
Measure	No Preoperative Oral Antibiotics n=43 Participants 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. ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)	Antibiotic n=43 Participants 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. nitrofurantoin monohydrate/macrocrystalline capsules: 1 week course of preoperative nitrofurantoin monohydrate/macrocrystalline capsules 100 milligrams twice daily ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)
Number of Participants With a Postoperative Fever Greater Than 38.3 Celsius	1 Participants	0 Participants

SECONDARY outcome

Timeframe: within 7 days following day of surgery

admission to ICU level nursing unit during primary hospitalization following kidney stone surgery (PCNL).

Outcome measures

Outcome measures
Measure	No Preoperative Oral Antibiotics n=43 Participants 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. ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)	Antibiotic n=43 Participants 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. nitrofurantoin monohydrate/macrocrystalline capsules: 1 week course of preoperative nitrofurantoin monohydrate/macrocrystalline capsules 100 milligrams twice daily ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)
Number of Participants Admitted to Intensive Care Unit (ICU) After Surgery	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Within 12 weeks following day of surgery

The Clavien-Dindo grading scale, originally described in 2004, is a widely used throughout surgery to grade adverse events (i.e. complications) which occur as a result of surgical procedures; it is used in most urology units and has become the standard classification system for many surgical specialities. The grading system uses a Grade I - Grade V scale, with Grade V being the most severe.

Outcome measures

Outcome measures
Measure	No Preoperative Oral Antibiotics n=43 Participants 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. ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)	Antibiotic n=43 Participants 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. nitrofurantoin monohydrate/macrocrystalline capsules: 1 week course of preoperative nitrofurantoin monohydrate/macrocrystalline capsules 100 milligrams twice daily ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)
Number and Grade of Postoperative Complications Following Surgery as Graded by the Clavien-Dindo Complication Scale Grade I	4 participants	8 participants
Number and Grade of Postoperative Complications Following Surgery as Graded by the Clavien-Dindo Complication Scale Grade II	5 participants	3 participants
Number and Grade of Postoperative Complications Following Surgery as Graded by the Clavien-Dindo Complication Scale Grade IIIA	1 participants	0 participants
Number and Grade of Postoperative Complications Following Surgery as Graded by the Clavien-Dindo Complication Scale Grade IIIB	4 participants	3 participants
Number and Grade of Postoperative Complications Following Surgery as Graded by the Clavien-Dindo Complication Scale Grade IV & V	0 participants	0 participants

SECONDARY outcome

Timeframe: Within 12 weeks following day of surgery

Number of days in a hospital setting after kidney stone surgery (defined as number of midnights in hospitalization)

Outcome measures

Outcome measures
Measure	No Preoperative Oral Antibiotics n=43 Participants 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. ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)	Antibiotic n=43 Participants 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. nitrofurantoin monohydrate/macrocrystalline capsules: 1 week course of preoperative nitrofurantoin monohydrate/macrocrystalline capsules 100 milligrams twice daily ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)
Hospital Length of Stay After Surgery	1.467 days Standard Deviation 1.147	1.097 days Standard Deviation 0.64

SECONDARY outcome

Timeframe: Within 12 weeks following day of surgery

the absence of stone fragments \>2mm on postoperative imaging following kidney stone surgery (PCNL)

Outcome measures

Outcome measures
Measure	No Preoperative Oral Antibiotics n=43 Participants 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. ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)	Antibiotic n=43 Participants 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. nitrofurantoin monohydrate/macrocrystalline capsules: 1 week course of preoperative nitrofurantoin monohydrate/macrocrystalline capsules 100 milligrams twice daily ampicillin: IV (2 g) gentamicin: IV (5 mg/kg) vancomycin: IV (1 g) ceftriaxone: IV (2 g)
Number of Partcipants That Were Stone Free After Surgery	25 Participants	22 Participants

Adverse Events

Antibiotic

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

No Preoperative Oral Antibiotics

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Paul Zupkas, Ph.D.

UCSD Medical Center

Phone: 6195432628

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place