Effect of Furosemide on ESWL Outcomes for Renal and Ureteral Calculi

Sponsor

Shiraz University of Medical Sciences (Other)

Overall Status

Recruiting

CT.gov ID

NCT05270421

Collaborator

(none)

500

Enrollment

Location

Arms

24.9

Anticipated Duration (Months)

20.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The minimally-invasive extracorporeal shockwave lithotripsy (ESWL) procedure is generally considered the best first-line treatment option for most adults and children with nephrolithiasis, especially when the calculi are smaller than 2 cm in size. Despite some promising results, few clinical trials have assessed the impact of furosemide on the outcome of ESWL. This study seeks to determine the effect of furosemide on ESWL outcomes when treating renal and ureteral calculi, hypothesizing that it will result in better outcomes for patients.

The present double-blind, randomized clinical trial includes 500 adults aged 18-60 years referring to the ESWL Clinic of Shahid Faghihi Hospital. Using block randomization, the patients are randomly assigned to one of two groups. All patients are to receive sedation with intravenous midazolam and 1000 ml of normal saline 30 minutes before ESWL. The only difference between the groups is that in the furosemide group, 40 mg of furosemide is added to the normal saline in the drug preparation room before administration. All patients are kept under heart monitoring and pulse oximetry until recovery. Pain will be checked for all participants via a telephone interview 24 hours later. The outcomes and possible side effects of ESWL will be evaluated for all patients after two and twelve weeks.

Condition or Disease	Intervention/Treatment	Phase
Urolithiasis Nephrolithiasis Urinary Calculi Ureterolithiasis	Drug: Furosemide 40 mg Other: Conventional Treatment	Phase 3

Detailed Description

The present study takes the form of a double-blind, randomized clinical trial. The study conforms to the principles stated in the Declaration of Helsinki. Written informed consent is obtained from all subjects prior to enrolment. All participants are made aware of the study protocol and can withdraw from the study at any point. Given that furosemide does not adversely affect patients who do not have cardiovascular or renal diseases, no complications are predicted. The trial is pending registration with clinicaltrials.gov. This protocol was conceived following the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines.

By taking into account an alpha error of 0.05 and a test power of 80%, the number of subjects in each group was calculated at 232. Considering a dropout rate of 10%, 250 subjects are to be included in each group.

Using block randomization, the patients are randomly assigned to one of two groups by a statistician outside of the research group. The codes for each group remain unknown to the researchers until after statistical analysis, with only the nurse and physician in charge of delivering the therapy and monitoring the patients being made aware.

All patients are to receive sedation with intravenous midazolam and 1000 ml of normal saline 30 minutes before ESWL, which is to be performed in the standard manner. The only difference between the groups is that in the furosemide group, 40 mg of furosemide is added to the normal saline in the drug preparation room before administration. All patients are kept under heart monitoring and pulse oximetry until recovery. Given that furosemide may theoretically cause pain secondary to hydronephrosis, pain will be checked for all participants via a telephone interview 24 hours later using a visual analog scale (VAS) of 0 to 10.

The outcomes and possible side effects of ESWL are evaluated for all patients after two and twelve weeks. A KUB X-ray is used for follow-up in patients with radiopaque stones, while a KUB CT scan is used otherwise. The primary outcome measure is the stone-free rate after two and twelve weeks, considered as the absence of a stone ≥ 4 mm. Secondary outcome measures include pain after 24 hours, need for re-ESWL, and need for surgery.

Before statistical analysis, adjudication of all measurements will be done by an experienced statistician outside of the research group. The adjudicator will assess the quality of each measurement and will exclude those with inadequate quality from the analysis, where they will be regarded as missing. Once the adjudication process is complete, the finalized database will be unblinded.

Data will be kept anonymous until analysis, which is to be performed by an independent statistician external to the research group. Data are analyzed using SPSS version 25 (IBM, Armonk, NY, USA). Quantitative variables will be compared using the independent t-test or Mann-Whitney U test as appropriate. Qualitative variables will be compared with the chi-squared test or Fisher's exact test as appropriate. Logistic regression will be used to compare the likelihood of success between the study groups after controlling for study variables. P-values below 0.05 indicate statistical significance in all cases.

The study's executive committee will report any adverse events to an independent Data and Safety and Monitoring Board (DSMB). The DSMB will halt the trial if patient safety is compromised or if the primary research objective is met. The DSMB will monitor all safety issues, and the DSMB statistician will report safety problems in each study group monthly. Any deaths will be investigated.

The Ethics Committee of Shiraz University of Medical Sciences approved the study protocol (code: IR.SUMS.MED.REC.1399.085). Informed consent will be obtained from all patients while they are clinically stable and not under the influence of sedatives. All participants are able to withdraw from the study at any point. Given that furosemide does not adversely affect patients who do not have cardiovascular or renal diseases, no complications were predicted. The principles of the Declaration of Helsinki will be upheld throughout this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

500 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

500 patients will be randomly and equally divided into the intervention and control groups.500 patients will be randomly and equally divided into the intervention and control groups.

Masking:

Double (Participant, Investigator)

Masking Description:

Primary Purpose:

Treatment

Official Title:

Effect of Furosemide on Outcome of Extracorporeal Shock Wave Lithotripsy for Renal and Ureteral Calculi; a Randomized, Triple-blinded, Controlled Trial

Actual Study Start Date :

Jul 1, 2020

Anticipated Primary Completion Date :

Mar 31, 2022

Anticipated Study Completion Date :

Jul 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention Group 40 mg of furosemide IV + IV midazolam + 1000 ml of normal saline 30 minutes before ESWL + Standard ESWL	Drug: Furosemide 40 mg Standard ESWL + Furosemide 40 mg Other: Conventional Treatment Standard ESWL
Active Comparator: Control Group IV midazolam + 1000 ml of normal saline 30 minutes before ESWL + Standard ESWL	Other: Conventional Treatment Standard ESWL

Arm

Intervention/Treatment

Experimental: Intervention Group

40 mg of furosemide IV + IV midazolam + 1000 ml of normal saline 30 minutes before ESWL + Standard ESWL

Drug: Furosemide 40 mg

Standard ESWL + Furosemide 40 mg

Other: Conventional Treatment

Standard ESWL

Active Comparator: Control Group

IV midazolam + 1000 ml of normal saline 30 minutes before ESWL + Standard ESWL

Other: Conventional Treatment

Standard ESWL

Outcome Measures

Primary Outcome Measures

Stone-free rate [2 weeks after intervention]
The absence of a stone ≥ 4 mm
Stone-free rate [3 months after intervention]
The absence of a stone ≥ 4 mm

Secondary Outcome Measures

Renal colic on VAS of 0-10 [24 hours after intervention]
Pain related to ureteral or renal calculi within 24 hours of ESWL
Number of participants with need for re-ESWL [Within 3 months after intervention]
The need for a repeated ESWL procedure
Number of participants with need for surgery [Within 3 months after intervention]
The need for a surgery to remove the stone

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18 to 60 years
Patients with renal or ureteral calculi referred by attending urologists to the ESWL Clinic of Shahid Faghihi Hospital, affiliated to Shiraz University of Medical Sciences (Shiraz, Iran)

Exclusion Criteria:

An anatomic anomaly in urinary system
Coagulopathy
Untreated urinary tract infection
Prior urologic surgery
Simultaneous unilateral renal and ureteral stones
Kidney failure (serum creatinine > 1.8 mg/dl)
Cardiovascular disease
Hypertension
Morbid obesity (BMI > 40 kg/m2)
History of allergy to furosemide, glibenclamide, hydrochlorothiazide, or acetazolamide.
Pregnancy
Single kidney