Ignite Creation Date:
2024-05-06 @ 8:46 AM
Last Modification Date:
2024-10-26 @ 12:05 PM
Study NCT ID:
NCT02829060
Status:
RECRUITING
Last Update Posted:
2020-03-24
First Post:
2016-05-31
Brief Title:
Endourology Disease Group Excellence EDGE Consortium Antibiotics Abx for Percutaneous Nephrolithotomy PCNL Part 2
Sponsor:
University of California San Diego
Organization:
University of California San Diego
Study Overview
Official Title:
The Endourology Disease Group for Excellence EDGE Consortium A Randomized Trial of Preoperative Prophylactic Antibiotics Prior to Percutaneous Nephrolithotomy in Patients With Moderate Risk of Postoperative Infection
Status:
RECRUITING
Status Verified Date:
2020-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PNLABXPART2
Brief Summary:
This study will be a multi-institutional randomized clinical trial of a short course of pre-operative antibiotic prophylaxis in addition to perioperative antibiotics prior to undergoing percutaneous nephrolithotomy The select patient population will be those patients deemed to be at a moderately increased risk of postoperative infectious complications These higher risk patients are those with indwelling urinary drainage tubes and those with a positive preoperative urine culture
Detailed Description:
This study will be a multi-institutional randomized clinical trial of a short course of pre-operative antibiotic prophylaxis in addition to perioperative antibiotics Once patients have been identified and enrolled into the study they will be grouped based on the sensitivity profiles of their positive urine culture or the presence of indwelling kidney drain tube nephrostomy tube nephroureteral stent ureteral stent Each of these groups will be individually randomized as follows
Group 1 Kidney stone subjects with indwelling drain tube nephrostomy tube or ureteral stent and negative urine culture
Randomization
7 day course of oral Macrobid Nitrofurantoin 100 mg twice daily 24 hours perioperative intravenous IV antibiotics
48 hours perioperative oral Macrobid Nitrofurantoin 100mg twice daily 24 hours perioperative IV antibiotics
Group 2 Kidney stone subjects with positive urine culture sensitive to oral antibiotics
Randomization
7 day course of an oral antibiotic proven effective on sensitivity profile 24 hours perioperative IV antibiotics
48 hours of an oral antibiotic proven effective on sensitivity profile 24 hours perioperative IV antibiotics
Macrobid is preferred oral agent if shown to be effective per culture sensitivities If patient has previous allergies to Macrobid andor sensitivity profile indicates ineffectiveness of Macrobid the one antibiotic will be provided in the order of choice nitrofurantoin sulfamethoxazole-trimethoprim doxycycline ciprofloxacin keflex cefpodoxime
Group 3 Kidney stone subject with positive urine culture sensitive to only intravenousintramuscular antibiotics resistant to oral agents
Randomization
7 day course of an IVIntramuscular IM antibiotic proven effective on sensitivity profile 24 hours perioperative IV antibiotics
48 hours of an IVIM antibiotic proven effective on sensitivity profile 24 hours perioperative IV antibiotics peripherally inserted central catheter PICC line IV or intramuscular injection for administration of antibiotics
The participating institutions are academic medical centers in the United States and Canada that are part of the EDGE Endourologic Disease Group of Excellence research consortium a research collaborative that has the goal of producing high quality multi-institutional studies of nephrolithiasis Separate IRB approvals will be obtained from each institution University of California San Diego UCSD will be the coordinating institution Member institution of EDGE maintain frequent email contact with one another and hold a monthly teleconference to discuss safety updates interim results issues with accrual and modifications to research protocols and consents if necessary
Treatment Assignments
Patients will be assigned based on a predetermined allocation sequence that will be generated by a computerized random number generator Patients will be stratified by institution in permuted blocks of varying size Only study staff at the coordinating institution UCSD will have access to the full allocation sequence ie no clinical staff involved in recruiting and consenting patients for the study at UCSD or other participating institutions will have knowledge of the allocation sequence at their institution prior to enrollment of each patient To further aid allocation concealment the block size will be varied
Standard of care procedures
Patients will be identified based on clinic visits or hospital admission All patients will be counseled on standard treatment options-extracorporeal shock wave lithotripsy ESWL percutaneous nephrolithotomy PCNL and ureteroscopy URS The discussion regarding treatment options and subsequent care will not deviate from routine care Patients consenting for percutaneous nephrolithotomy PCNL will be considered for enrollment into the study and will be enrolled to have data collected prospectively Patients will be consented prior to prescription of antibiotics and to the surgery for collection of demographic disease perioperative and postoperative data Abdominal pelvic computed tomography CT if not already obtained will be used to delineate pre-operative stone size and for preoperative planning If the patient does not consent to the study the use of antibiotics will be based on routine clinical practice of the treating urologist Both prophylaxis with preoperative antibiotics and no prophylaxis ie periprocedural only are considered standard of care
Investigational portion of treatment
Group 1 patients will be randomized to nitrofurantoin monohydratemacrocrystalline 100 mg twice daily for 7 days prior to PCNL with the final day of prophylactic course being 1 day prior to surgery or to nitrofurantoin monohydratemacrocrystalline 100mg twice daily for 48 hours prior to PCNL Nitrofurantoin monohydratemacrocrystalline is currently indicated for the treatment of acute uncomplicated urinary tract infections Both groups will receive antibiotics the day of surgery-ie a dose of ampicillin intravenous IV 2 g and gentamicin intravenous IV 5 mgkg within 120 minutes of surgery start time Patients with penicillin allergy will receive vancomycin intravenous IV 1 g instead of ampicillin and patients with gentamicinaminoglycoside allergy will receive ceftriaxone intravenous IV 2 g instead of gentamicin Postoperative antibiotics in the absence of sepsis see definition of sepsis below will be 24 hours of IV antibiotics
Group 2 patients will be randomized to either 7 days or 48 hours of oral antibiotics prior to the PCNL with the final day of prophylactic course being 1 day prior to surgery Antibiotic choice will be determined by the culture sensitivity profile with nitrofurantoin monohydratemacrocrystalline 100 mg twice daily being the preferred agent if shown to be effective against the uropathogens If patient has previous allergies to Macrobid andor sensitivity profile indicates ineffectiveness of Macrobid then one antibiotic will be provided in the following order nitrofurantoin sulfamethoxazole-trimethoprim doxycycline ciprofloxacin keflex cefpodoxime
Antibiotics the day of surgery will be a dose of ampicillin IV 2g and gentamicin IV 5mgkg within 120 minutes of surgery start time Patients with penicillin allergy will receive vancomycin IV 1g instead of ampicillin and patients with gentamicinaminoglycoside allergy will receive ceftriaxone IV 2g instead of gentamicin Postoperative antibiotics in the absence of sepsis see definition of sepsis below will be 24 hours of IV antibiotics
Group 3 patients will be randomized to either 7 days or 48 hours of an injectable IVIM antibiotic prior to the PCNL with the final day of prophylaxis being 1 day before surgery Antibiotic choice will be determined by the culture sensitivity profile
Antibiotics the day of surgery will be a dose of same IVIM antibiotic within 120 minutes of surgery start time Postoperative antibiotics in the absence of sepsis see definition of sepsis below will be 24 hours of IV antibiotics
Central randomization will take place with UCSD as the lead site Randomization will occur in block randomization in block sizes of 10
Standard of care procedures
Patients will have PCNL performed in typical fashion without deviation from standard of care Per the usual practice of the treating surgeon percutaneous access to the kidney will be obtained either by Interventional Radiology or by the operating surgeon At the time of surgery urine from the renal pelvis urine from the bladder and the stone itself will be sent for culture Placement of renal drainage devices ureteral stents nephrostomy tubes nephroureteral stents will be left up to the discretion of the surgeon Post-operatively the patients will be admitted to the hospital and monitored per usual clinical procedure Unless clinically indicated as described above 24 hours of post-operative antibiotics will be prescribed Labs will be obtained pre-operatively and on post-operative day 1 if the patient is admitted and will include complete blood count CBC basic metabolic panel chem 7 Further laboratory tests will be dictated by the patients clinical status as per the standard of care-ie for patients that exhibit signs of sepsis such as tachycardia 90min low systolic blood pressure 90 mmHg fever 383 Celsius hypothermia 36 Celsius altered mental status respiratory rate 20 min or leukocytosis 12000 or leukopenia 4000 further urine culture blood culture and serum lactate will be obtained
The patient will be discharged from the hospital per the usual clinical protocols Post-discharge the patient will be seen in clinic 1-12 weeks after surgery Patients will undergo a non-contrast CT abdomenpelvis an abdominal plain radiograph andor a renal ultrasound during this postoperative period
Demographic fields will be obtained preoperatively and include age race gender American Society of Anesthesiologists ASA score for comorbidity assessment body mass index BMI and prior stone disease Disease fields that will be obtained include stone size maximal axial and coronal dimensions degree of hydronephrosis mildmoderatesevere history of diabetes mellitus history of cardiac disease hypertension prior urinary tract infection history of bowel diversion or neurogenic bladder
Perioperative fields include OR surgical time type of anesthesia number of access tracts use of internalized ureteral stent nephrostomy tube or nephroureteral stent estimated blood loss and intraoperative complications Postoperative fields will include postoperative maximum body temperature heart rate respiratory rate urine culture results stone culture results stone composition white blood cell count serum lactate postoperative serum creatinine need for admission to intensive care unit hospital length of stay LOS and stone-free status at 1-12 week postoperative imaging Patients will be followed during routine clinical visits as part of their continuing care
Group 1 Kidney stone subjects with indwelling drain tube nephrostomy tube or ureteral stent and negative urine culture
Randomization
7 day course of oral Macrobid Nitrofurantoin 100 mg twice daily 24 hours perioperative intravenous IV antibiotics
48 hours perioperative oral Macrobid Nitrofurantoin 100mg twice daily 24 hours perioperative IV antibiotics
Group 2 Kidney stone subjects with positive urine culture sensitive to oral antibiotics
Randomization
7 day course of an oral antibiotic proven effective on sensitivity profile 24 hours perioperative IV antibiotics
48 hours of an oral antibiotic proven effective on sensitivity profile 24 hours perioperative IV antibiotics
Macrobid is preferred oral agent if shown to be effective per culture sensitivities If patient has previous allergies to Macrobid andor sensitivity profile indicates ineffectiveness of Macrobid the one antibiotic will be provided in the order of choice nitrofurantoin sulfamethoxazole-trimethoprim doxycycline ciprofloxacin keflex cefpodoxime
Group 3 Kidney stone subject with positive urine culture sensitive to only intravenousintramuscular antibiotics resistant to oral agents
Randomization
7 day course of an IVIntramuscular IM antibiotic proven effective on sensitivity profile 24 hours perioperative IV antibiotics
48 hours of an IVIM antibiotic proven effective on sensitivity profile 24 hours perioperative IV antibiotics peripherally inserted central catheter PICC line IV or intramuscular injection for administration of antibiotics
The participating institutions are academic medical centers in the United States and Canada that are part of the EDGE Endourologic Disease Group of Excellence research consortium a research collaborative that has the goal of producing high quality multi-institutional studies of nephrolithiasis Separate IRB approvals will be obtained from each institution University of California San Diego UCSD will be the coordinating institution Member institution of EDGE maintain frequent email contact with one another and hold a monthly teleconference to discuss safety updates interim results issues with accrual and modifications to research protocols and consents if necessary
Treatment Assignments
Patients will be assigned based on a predetermined allocation sequence that will be generated by a computerized random number generator Patients will be stratified by institution in permuted blocks of varying size Only study staff at the coordinating institution UCSD will have access to the full allocation sequence ie no clinical staff involved in recruiting and consenting patients for the study at UCSD or other participating institutions will have knowledge of the allocation sequence at their institution prior to enrollment of each patient To further aid allocation concealment the block size will be varied
Standard of care procedures
Patients will be identified based on clinic visits or hospital admission All patients will be counseled on standard treatment options-extracorporeal shock wave lithotripsy ESWL percutaneous nephrolithotomy PCNL and ureteroscopy URS The discussion regarding treatment options and subsequent care will not deviate from routine care Patients consenting for percutaneous nephrolithotomy PCNL will be considered for enrollment into the study and will be enrolled to have data collected prospectively Patients will be consented prior to prescription of antibiotics and to the surgery for collection of demographic disease perioperative and postoperative data Abdominal pelvic computed tomography CT if not already obtained will be used to delineate pre-operative stone size and for preoperative planning If the patient does not consent to the study the use of antibiotics will be based on routine clinical practice of the treating urologist Both prophylaxis with preoperative antibiotics and no prophylaxis ie periprocedural only are considered standard of care
Investigational portion of treatment
Group 1 patients will be randomized to nitrofurantoin monohydratemacrocrystalline 100 mg twice daily for 7 days prior to PCNL with the final day of prophylactic course being 1 day prior to surgery or to nitrofurantoin monohydratemacrocrystalline 100mg twice daily for 48 hours prior to PCNL Nitrofurantoin monohydratemacrocrystalline is currently indicated for the treatment of acute uncomplicated urinary tract infections Both groups will receive antibiotics the day of surgery-ie a dose of ampicillin intravenous IV 2 g and gentamicin intravenous IV 5 mgkg within 120 minutes of surgery start time Patients with penicillin allergy will receive vancomycin intravenous IV 1 g instead of ampicillin and patients with gentamicinaminoglycoside allergy will receive ceftriaxone intravenous IV 2 g instead of gentamicin Postoperative antibiotics in the absence of sepsis see definition of sepsis below will be 24 hours of IV antibiotics
Group 2 patients will be randomized to either 7 days or 48 hours of oral antibiotics prior to the PCNL with the final day of prophylactic course being 1 day prior to surgery Antibiotic choice will be determined by the culture sensitivity profile with nitrofurantoin monohydratemacrocrystalline 100 mg twice daily being the preferred agent if shown to be effective against the uropathogens If patient has previous allergies to Macrobid andor sensitivity profile indicates ineffectiveness of Macrobid then one antibiotic will be provided in the following order nitrofurantoin sulfamethoxazole-trimethoprim doxycycline ciprofloxacin keflex cefpodoxime
Antibiotics the day of surgery will be a dose of ampicillin IV 2g and gentamicin IV 5mgkg within 120 minutes of surgery start time Patients with penicillin allergy will receive vancomycin IV 1g instead of ampicillin and patients with gentamicinaminoglycoside allergy will receive ceftriaxone IV 2g instead of gentamicin Postoperative antibiotics in the absence of sepsis see definition of sepsis below will be 24 hours of IV antibiotics
Group 3 patients will be randomized to either 7 days or 48 hours of an injectable IVIM antibiotic prior to the PCNL with the final day of prophylaxis being 1 day before surgery Antibiotic choice will be determined by the culture sensitivity profile
Antibiotics the day of surgery will be a dose of same IVIM antibiotic within 120 minutes of surgery start time Postoperative antibiotics in the absence of sepsis see definition of sepsis below will be 24 hours of IV antibiotics
Central randomization will take place with UCSD as the lead site Randomization will occur in block randomization in block sizes of 10
Standard of care procedures
Patients will have PCNL performed in typical fashion without deviation from standard of care Per the usual practice of the treating surgeon percutaneous access to the kidney will be obtained either by Interventional Radiology or by the operating surgeon At the time of surgery urine from the renal pelvis urine from the bladder and the stone itself will be sent for culture Placement of renal drainage devices ureteral stents nephrostomy tubes nephroureteral stents will be left up to the discretion of the surgeon Post-operatively the patients will be admitted to the hospital and monitored per usual clinical procedure Unless clinically indicated as described above 24 hours of post-operative antibiotics will be prescribed Labs will be obtained pre-operatively and on post-operative day 1 if the patient is admitted and will include complete blood count CBC basic metabolic panel chem 7 Further laboratory tests will be dictated by the patients clinical status as per the standard of care-ie for patients that exhibit signs of sepsis such as tachycardia 90min low systolic blood pressure 90 mmHg fever 383 Celsius hypothermia 36 Celsius altered mental status respiratory rate 20 min or leukocytosis 12000 or leukopenia 4000 further urine culture blood culture and serum lactate will be obtained
The patient will be discharged from the hospital per the usual clinical protocols Post-discharge the patient will be seen in clinic 1-12 weeks after surgery Patients will undergo a non-contrast CT abdomenpelvis an abdominal plain radiograph andor a renal ultrasound during this postoperative period
Demographic fields will be obtained preoperatively and include age race gender American Society of Anesthesiologists ASA score for comorbidity assessment body mass index BMI and prior stone disease Disease fields that will be obtained include stone size maximal axial and coronal dimensions degree of hydronephrosis mildmoderatesevere history of diabetes mellitus history of cardiac disease hypertension prior urinary tract infection history of bowel diversion or neurogenic bladder
Perioperative fields include OR surgical time type of anesthesia number of access tracts use of internalized ureteral stent nephrostomy tube or nephroureteral stent estimated blood loss and intraoperative complications Postoperative fields will include postoperative maximum body temperature heart rate respiratory rate urine culture results stone culture results stone composition white blood cell count serum lactate postoperative serum creatinine need for admission to intensive care unit hospital length of stay LOS and stone-free status at 1-12 week postoperative imaging Patients will be followed during routine clinical visits as part of their continuing care
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None