Contrast-enhanced Ultrasound Versus CT Scan for Kidney Stone Patient Management (CEUS)

Contrast-enhanced Ultrasound Versus CT Scan for Kidney Stone Patient

This study will be a randomized controlled study comparing the use of two clinical management strategies in nephrostomy tube management following percutaneous nephrolithotomy (PCNL). The first strategy entails using contrast-enhanced ultrasound (CEUS) to evaluate the renal collecting system (1). This is a new imaging approach applying ultrasound machines with special software in combination with intraluminal ultrasound contrast agent (Lumason) injection, which is an FDA-approved ultrasound contrast agent (2). The second strategy is a nephrostomy tube capping trial combined with low dose non-contrast computed tomography (CT) scan, one of the most frequently utilized clinical management strategies currently used in clinical practice (3).

Study Overview

• Status: Withdrawn
• Conditions: Nephrolithiasis; Ultrasonography
• Intervention / Treatment: Drug: CEUS; Diagnostic test: Non-contrast CT scan; Diagnostic test: Capping trial

Detailed Description

This is a multi-center, randomized controlled study comparing the use of CEUS to CT scan plus capping trial immediately following PCNL. A total recruitment target of 1,046 subjects is planned and participants will be randomized into one of the two study arms.

1. Contrast-enhanced ultrasound (CEUS) arm: On postoperative day 1 (unless not clinically indicated), each subject will undergo CEUS with an administration of Lumason via their pre-placed nephrostomy tube.
2. Non-contrast CT scan plus capping trial arm: On postoperative day 1 (unless not clinically indicated), subjects' pre-placed nephrostomy tube will be capped and they will undergo a low dose non-contrast abdominal CT scan.

Subsequently, nephrostomy tubes will be managed based on the results from these studies by the treating surgeon.

Screening data will be reviewed to determine subject eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria will be entered into the study.

The following investigational regimen will be used only in the CEUS arm:

Experimental Investigation: Lumason at a 2 mL single dose, repeatable once at the time of imaging as needed.

Subjects will be exposed to the randomization schema for 1 day during which they will undergo one of the two diagnostic imaging pathways. After that imaging study is complete, clinical care will proceed as per norm. Clinical and imaging data will be prospectively collected from the time of initial presentation until 6 months after surgery. The total duration of the study is expected to be 5 years to reach target accrual. Therefore, the investigators anticipate that the total duration of this study will be 4 years and 6 months for patient recruitment with the final 6 months used for collecting follow up data.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age of 18 years or older.
• Renal and/or ureteral stone of any size diagnosed either by ultrasound or CT scan and requiring surgical treatment with percutaneous removal (PCNL).

Exclusion Criteria:

• A second stage PCNL is planned or expected after surgery, entailing that postoperative tube management is pre-determined.
• Subjects with serious illness likely to cause death within the next 5 years, so as to exclude significant metabolic derangements that might lead to adverse surgical outcome.
• Subjects with a history of hypersensitivity reactions to sulfur hexafluoride lipid microsphere components or to any of the inactive ingredients in Lumason
• Pregnancy, which is a contraindication to both CT scan and ultrasound contrast injection.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CEUS arm; On postoperative day 1 (unless not clinically indicated), each subject will undergo CEUS with an administration of Lumason via their pre-placed nephrostomy tube.	Drug: CEUS; In subjects randomized into the CEUS arm, 2 mL of Lumason will be injected as a single dose via a nephrostomy tube at the time of postoperative renal ultrasound, following by 5 mL of normal saline flush. Subjects will be given up to one additional dose injected in the same fashion as indicated during the imaging study to confirm opacification of the ureter.; Other Names: Contrast-enhanced ultrasound, CEUS nephrostogram
Active Comparator: CT scan plus capping trial arm; On postoperative day 1 (unless not clinically indicated), subjects' pre-placed nephrostomy tube will be capped and they will undergo a low dose non-contrast abdominal CT scan.	Diagnostic test: Non-contrast CT scan; The CT scan performed in this study arm is regularly performed to evaluate the kidney and look for residual stones after surgery both at UCSF and around the world. It does not require contrast injection, so risks from contrast allergy or any injection are absent. A low dose protocol will be used, and therefore, subjects will be exposed to a very small amount of ionizing radiation as low as 1-2 mSv if randomized into this arm.; Other Names: NCCT; Diagnostic test: Capping trial; Subjects who are randomized into this study arm will undergo both nephrostomy tube capping and a low dose non-contrast CT scan on the first day after surgery. Successfully passing a capping trial is defined as the absence of fever, worsened flank pain, and leakage around the nephrostomy tube within 4 hours after capping the tube.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiation exposure dose	For radiation exposure dose measurement in this study, the investigators will use dose metrics obtained from the Digital Imaging and Communications within the scanners or Picture Arching and Communication system (PACS).	6 months following surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of adverse clinical events	Defined as postoperative complications and any unplanned surgery related to the patient's kidney stone	6 months following surgery

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Oregon Health and Science University
• Investigators: Principal Investigator: Thomas Chi, MD, UCSF Department of Urology

Publications and helpful links

General Publications

• Chi T, Usawachintachit M, Mongan J, Kohi MP, Taylor A, Jha P, Chang HC, Stoller M, Goldstein R, Weinstein S. Feasibility of Antegrade Contrast-enhanced US Nephrostograms to Evaluate Ureteral Patency. Radiology. 2017 Apr;283(1):273-279. doi: 10.1148/radiol.2016160959. Epub 2016 Oct 19.
• Lumason: Prescribing Information [Internet]. [cited 2017 Jan 21]. Available from: http://www.braccoimaging.com/us-en/products-and-solutions/contrast-enhanced-ultrasound/lumason/prescribing-information
• Sountoulides P, Metaxa L, Cindolo L. Is computed tomography mandatory for the detection of residual stone fragments after percutaneous nephrolithotomy? J Endourol. 2013 Nov;27(11):1341-8. doi: 10.1089/end.2012.0253. Epub 2013 Jul 9.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 30, 2017
• Primary Completion (Actual): May 2, 2022
• Study Completion (Actual): May 2, 2022

Study Registration Dates

• First Submitted: February 16, 2017
• First Submitted That Met QC Criteria: February 16, 2017
• First Posted (Actual): February 23, 2017

Study Record Updates

• Last Update Posted (Actual): June 6, 2022
• Last Update Submitted That Met QC Criteria: June 1, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Contrast-enhanced ultrasound; Percutaneous nephrolithotomy
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Pathological Conditions, Anatomical; Urolithiasis; Urinary Calculi; Calculi; Kidney Calculi; Nephrolithiasis
• Other Study ID Numbers: 17-21497; R21DK109433 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No