Effect of Furosemide on ESWL Outcomes for Renal and Ureteral Calculi

February 26, 2022 updated by: Seyed Hossein Hosseini, Shiraz University of Medical Sciences

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

500

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Stone-free rate
Time Frame: 2 weeks after intervention
The absence of a stone ≥ 4 mm
2 weeks after intervention
Stone-free rate
Time Frame: 3 months after intervention
The absence of a stone ≥ 4 mm
3 months after intervention

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shiraz University of Medical Sciences

Investigators

  • Study Director: Dariush Irani, MD, Department of Urology, School of Medicine, Shiraz University of Medical Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

July 1, 2020

Primary Completion (ANTICIPATED)

March 31, 2022

Study Completion (ANTICIPATED)

July 30, 2022

Study Registration Dates

First Submitted

February 12, 2022

First Submitted That Met QC Criteria

February 26, 2022

First Posted (ACTUAL)

March 8, 2022

Study Record Updates

Last Update Posted (ACTUAL)

March 8, 2022

Last Update Submitted That Met QC Criteria

February 26, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 21179-01-01-98

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Yes We plan to publish the study protocol soon. The final results will be published in the form of an article after the study is completed.

IPD Sharing Time Frame

We plan to publish the study protocol within six months.

IPD Sharing Access Criteria

Supporting data will be made available upon reasonable request. All inquiries should be sent to Dr. Seyed Hossein Hosseini.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe