Enhanced Versus Extended Preoperative Antibiotic Prophylaxis Regimens for Retrograde Intrarenal Surgery in High Infectious Risk Patients: Randomized Controlled Trial

Sponsor

Mansoura University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05384197

Collaborator

(none)

280

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Renal Stone	Drug: Enhanced regimen Drug: Extended regimen	Phase 3

Detailed Description

Retrograde intrarenal surgery (RIRS) has gained a wide popularity in the management of renal stones due to tremendous technological advancements over the last years. According to the current guidelines, RIRS could be offered as a first line surgical treatment option for renal stones less than 20 mm (or ≤ 10 mm for lower pole stone/s) with favorable stone free rate (SFR).

Despite being a minimally invasive, several morbid complications could be encountered during/after RIRS. Post-operative infectious complications constitute one of the major reported complications after RIRS with varying presentations which include urosepsis, febrile urinary tract infection (UTI) and asymptomatic bacteriuria.

Several large-populations studies have reported the incidence of infectious complications post-RIRS. Among ≈ 12.000 patients undergoing ureteroscopy and were evaluated by The Clinical Research Office of Endourological Society (CROES), post-operative fever, UTI and urosepsis were reported in 1.8%, 1.3% and 0.3%, respectively. Moreover, in another report by Reducing Operative Complications from Kidney stones (ROCK) for 1.817 patients undergoing RIRS, 2.4% required hospital readmission (HR) for infectious complications.

The underlying mechanisms of infectious complications post-RIRS include combination of existing bacteria in the urinary tract and rising intrarenal pressure due to prolonged and/or vigorous irrigation. In addition, several studies have investigated the independent predictors of infectious complications after RIRS with identified positive preoperative urine culture or prior history of recurrent UTI (8), long-lasting indwelling ureteral stents, diabetes mellitus (DM) and immunocompromised patients.

In addition to the substantial patient morbidity, post-operative infectious complications constitute a major burden to the health care resources. Therefore, minimizing these devastating events should an important consideration by health care providers not only for improving the patient satisfaction but also for cost-saving issues. Therefore, it is a crucial entity for clinicians to identify high-risk patients for post-RIRS infectious complications and to exhaust the different clinical mitigations to minimize these events.

According to American Urological Association (AUA) Best Practice Statements on Antibiotic Prophylaxis (AP), single dose of perioperative antibiotics is indicated for all cases prior to RIRS. However, the exact regimen and duration of preoperative AP for high risk patients for infectious complication are still undefined.

In previous studies on AP for high risk patients prior to percutaneous nephrolithotomy (PCNL), different protocols were compared as regard to its impact on infectious events after PCNL. Despite the reported advantage of the extended regimen on minimizing the infectious events, we should consider the drawbacks of prolonged antibiotics as untoward adverse events (AEs) and drug resistance

Study Design

Study Type:

Interventional

Anticipated Enrollment :

280 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

In the available literature, we lack the risk categorization of infectious complications after RIRS with subsequent recommendation as regard to AP in different risk patients. Therefore we are planning to investigate the optimal protocol for AP prior to RIRS in high-risk population through comparing the enhanced regimen (2days) vs. the extended regimen (7 days) in a randomized controlled trial (RCT).In the available literature, we lack the risk categorization of infectious complications after RIRS with subsequent recommendation as regard to AP in different risk patients. Therefore we are planning to investigate the optimal protocol for AP prior to RIRS in high-risk population through comparing the enhanced regimen (2days) vs. the extended regimen (7 days) in a randomized controlled trial (RCT).

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Enhanced Versus Extended Preoperative Antibiotic Prophylaxis Regimens for Retrograde Intrarenal Surgery in High Infectious Risk Patients: Randomized Controlled Trial

Actual Study Start Date :

May 1, 2022

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Enhanced regimen They will receive two days antibiotic prophylaxis according to the predetermined protocol. Sulfamethoxazole-Trimethoprim (TMP-SMX) twice daily will be utilized as the first choice AP for 2 days according to the assigned randomization group with the last day of AP course being one day prior to intervention. In patients with allergy or resistance to TMP-SMX, the following antibiotics will be considered in the following order: 100 mg Nitrofurantoin twice daily, 500 mg Ciprofloxacin twice daily or 200 mg Cefpodoxime twice daily. Patients with positive culture which is sensitive only to parenteral antibiotics will receive culture-based intramuscular/intravenous antibiotics following the same schedule (2 days with the last day of AP course being one day prior to intervention)	Drug: Enhanced regimen Sulfamethoxazole-Trimethoprim (TMP-SMX) twice daily will be utilized as the first choice AP for 2 days with the last day of AP course being one day prior to intervention. In patients with allergy or resistance to TMP-SMX, the following antibiotics will be considered in the following order: 100 mg Nitrofurantoin twice daily, 500 mg Ciprofloxacin twice daily or 200 mg Cefpodoxime twice daily. Patients with positive culture which is sensitive only to parenteral antibiotics will receive culture-based intramuscular/intravenous antibiotics following the same schedule (2 days with the last day of AP course being one day prior to intervention)
Active Comparator: Extended regimen They will receive seven days antibiotic prophylaxis according to the predetermined protocol. Sulfamethoxazole-Trimethoprim (TMP-SMX) twice daily will be utilized as the first choice AP for 7 days with the last day of AP course being one day prior to intervention. In patients with allergy or resistance to TMP-SMX, the following antibiotics will be considered in the following order: 100 mg Nitrofurantoin twice daily, 500 mg Ciprofloxacin twice daily or 200 mg Cefpodoxime twice daily. Patients with positive culture which is sensitive only to parenteral antibiotics will receive culture-based intramuscular/intravenous antibiotics following the same schedule ( 7 days with the last day of AP course being one day prior to intervention)	Drug: Extended regimen Sulfamethoxazole-Trimethoprim (TMP-SMX) twice daily will be utilized as the first choice AP for 7 days with the last day of AP course being one day prior to intervention. In patients with allergy or resistance to TMP-SMX, the following antibiotics will be considered in the following order: 100 mg Nitrofurantoin twice daily, 500 mg Ciprofloxacin twice daily or 200 mg Cefpodoxime twice daily. Patients with positive culture which is sensitive only to parenteral antibiotics will receive culture-based intramuscular/intravenous antibiotics following the same schedule (7 days with the last day of AP course being one day prior to intervention)

Arm

Intervention/Treatment

Active Comparator: Enhanced regimen

They will receive two days antibiotic prophylaxis according to the predetermined protocol. Sulfamethoxazole-Trimethoprim (TMP-SMX) twice daily will be utilized as the first choice AP for 2 days according to the assigned randomization group with the last day of AP course being one day prior to intervention. In patients with allergy or resistance to TMP-SMX, the following antibiotics will be considered in the following order: 100 mg Nitrofurantoin twice daily, 500 mg Ciprofloxacin twice daily or 200 mg Cefpodoxime twice daily. Patients with positive culture which is sensitive only to parenteral antibiotics will receive culture-based intramuscular/intravenous antibiotics following the same schedule (2 days with the last day of AP course being one day prior to intervention)

Drug: Enhanced regimen

Sulfamethoxazole-Trimethoprim (TMP-SMX) twice daily will be utilized as the first choice AP for 2 days with the last day of AP course being one day prior to intervention. In patients with allergy or resistance to TMP-SMX, the following antibiotics will be considered in the following order: 100 mg Nitrofurantoin twice daily, 500 mg Ciprofloxacin twice daily or 200 mg Cefpodoxime twice daily. Patients with positive culture which is sensitive only to parenteral antibiotics will receive culture-based intramuscular/intravenous antibiotics following the same schedule (2 days with the last day of AP course being one day prior to intervention)

Active Comparator: Extended regimen

They will receive seven days antibiotic prophylaxis according to the predetermined protocol. Sulfamethoxazole-Trimethoprim (TMP-SMX) twice daily will be utilized as the first choice AP for 7 days with the last day of AP course being one day prior to intervention. In patients with allergy or resistance to TMP-SMX, the following antibiotics will be considered in the following order: 100 mg Nitrofurantoin twice daily, 500 mg Ciprofloxacin twice daily or 200 mg Cefpodoxime twice daily. Patients with positive culture which is sensitive only to parenteral antibiotics will receive culture-based intramuscular/intravenous antibiotics following the same schedule ( 7 days with the last day of AP course being one day prior to intervention)

Drug: Extended regimen

Sulfamethoxazole-Trimethoprim (TMP-SMX) twice daily will be utilized as the first choice AP for 7 days with the last day of AP course being one day prior to intervention. In patients with allergy or resistance to TMP-SMX, the following antibiotics will be considered in the following order: 100 mg Nitrofurantoin twice daily, 500 mg Ciprofloxacin twice daily or 200 mg Cefpodoxime twice daily. Patients with positive culture which is sensitive only to parenteral antibiotics will receive culture-based intramuscular/intravenous antibiotics following the same schedule (7 days with the last day of AP course being one day prior to intervention)

Outcome Measures

Primary Outcome Measures

Rate of postoperative sepsis [30 days after intervention]
Postoperative sepsis is defined as severe post-procedural (within 12 hours after the procedure with coexisting positive urine culture) infectious complication with ≥ two of the following findings: - Body temperature more than 38.3C or below 36C. - Tachycardia (>90/minute). - Respiratory rate more than 20/minute. - Disturbed mental status. - Systolic blood pressure < 90 mmHg & mean arterial pressure < 70 mmHg or systolic blood pressure decrease < 40 mmHg. - WBC >12,000 or <4,000.

Secondary Outcome Measures

Rate of postoperative fever [30 days after intervention]
Rate of postoperative UTI [30 days after intervention]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Ability to give informed consent.
Age ≥18 years.
Renal stone <20 mm in which RIRS is recommended.
High susceptibility of post-procedural infectious complications by one or more of the followings: - Positive preoperative urine culture within 12 weeks of the planned intervention. -Indwelling ureteral stents for more than 4 weeks. -Diabetes mellitus.