Clinical trial NCT02863770: Contrast EUS of the Pancreas
Official title: Prospective Controlled Trial of Contrast Enhanced Endoscopic Ultrasound for Evaluation of Pancreas Lesions
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pancreatic Neoplasms
Pancreatitis
Pancreatic Cyst
Keywords: endosonography
Lead sponsor: University of Southern California
Sponsor class: OTHER
First posted: 2016-08-11
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: RATIONALE: Endoscopic Ultrasound (EUS) is the leading method to evaluate the pancreas but there may be difficulty characterizing small lesions, tumors which are not adenocarcinomas and neoplasia in the setting of pancreatitis.

INTERVENTION: The innovation in this project will be the addition of intravenous contrast to standard EUS examination if the pancreas.

PURPOSE: The aim is to determine if contrast enhances the ability of EUS to accurately diagnose lesions and target biopsies, and to define the quantitative features of this method.

STUDY POPULATION:The population will include patients with pancreas cysts, masses, and inflammation presenting for EUS as part of standard clinical care.

METHODOLOGY: This will be a prospective tandem trial involving conventional EUS, followed by EUS with contrast, followed by subsequent quantitative processing of contrast EUS imaging.

ENDOINTS:Study endpoints will include the yield contrast EUS to evaluate pancreas cysts, masses, and inflammation. The impact of contrast EUS to better target the FNA of the chosen lesion will be assessed. Intra and interobserver variability will be assessed by comparing conventional EUS and contrast EUS of each case in a random order (intraobserver agreement) and among a group of blinded endosonographers (interobserver agreement).

Detailed description: AIM Early detection of pancreas cancer and precursors lesions improves survival. The investigators aim is to gauge whether quantitative contrast endoscopic ultrasound (EUS) improves the evaluation of pancreas tumors and precursors lesions including cysts.

DESIGN The study will be a prospective tandem contrast EUS trial. All EUS will be performed as part of standard clinical care.

Conventional EUS Standard EUS will first be performed using the 180 series linear array echoendoscope (Olympus, Center Valley, PA). The alpha-10 image processor (Aloka America, Wallingford, CT) in B mode will be used to acquire images. A research coordinator will help to record key parameters. Thirty second cine clips of conventional EUS images will be captured to compare with contrast EUS clips and enable intra and interobserver variability comparison.

Contrast Administration Definity contrast will be activated by 45 seconds of agitation (VialMix, Lantheus, North Billerica, MA) and injected through the intravenous peripheral line which is placed to administer fluids. The investigators will administer a bolus dose of 10microliter (microL)/kg within 30-60 seconds followed by 10ml of saline flush. Up to 2 bolus injections will be administered during each case and doppler sonography will be used between them to induce microbubble destruction.

Contrast EUS: Following contrast administration prospective assessment will be performed using the Olympus endoscope and images processed using the Alpha 10 system. Harmonic detection conversion software installed on the alpha 10 processor to enable detection. Core parameters for comparison to conventional EUS will be captured prospectively.

Quantitative Processing: For each bolus 30 seconds of cine imaging will be captured for post processing and for comparison with conventional EUS imaging (intra and interobserver variability). Images of the lesion (5mm x 5mm region) and adjacent normal tissue (5mm x 5mm) regions will be captured to facilitate quantitative assessment. Quantitative analytic software will then be used to generate time intensity curves and associated values including peak intensity (PI), time to peak (TTP), wash-in-slope (WIS), rise time (RT), mean transit time (MTT), and time from peak to one-half (TPH).

DRUG/DEVICE INFORMATION

Definity: Definity is an intravenous contrast agent. It is comprised of 1.1-3.3um micropheres containing perflutren (octafluoropropane) which is cleared by respiration.

The gas is encapsulated lipid shells which are metabolized to free fatty acids and hepatically cleared.

The Olympus 180 linear echoendoscope will be used in all procedures which are being done for standard clinical indications. The Aloka SSD-Alpha 10-Processor will be used for image capture. Post EUS quantitative processing will be performed using QLAB quantification software (Philips Healthcare, Bothel, WA).

Eligibility criteria: Inclusion Criteria:

* Patients undergoing endoscopic ultrasound for standard pancreatic indications.
* Patients must have unexplained pancreatitis, pancreas mass(es), or pancreatic cystic lesions (\>1cm or worrisome features on imaging).

Exclusion Criteria:

* Patients \<18 years of age, pregnant women, and lactating mothers will be excluded. Subjects with unstable ischemic disease will be excluded. Additionally, those with known or suspected right-to-left, bi-directional, or transient right-to-left cardiac shunts will be excluded given theoretical (though clinically insignificant) risk of embolization.
* Patients with an allergy to Definity will be excluded.

Primary outcomes:
measure: The yield of EUS versus contrast EUS to diagnose pancreas cystic lesions, mass lesion, and origin of pancreatitis.
timeFrame: 6 months
Secondary outcomes:
measure: Targeting of FINE NEEDLE ASPIRATION (FNA) of pancreas lesions.
timeFrame: 6 months
measure: Quantitative Parameters of Pancreas Lesions
timeFrame: 6 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Los Angeles County Hospital
state: California
Study officials:
References:
citation: Napoleon B, Alvarez-Sanchez MV, Gincoul R, Pujol B, Lefort C, Lepilliez V, Labadie M, Souquet JC, Queneau PE, Scoazec JY, Chayvialle JA, Ponchon T. Contrast-enhanced harmonic endoscopic ultrasound in solid lesions of the pancreas: results of a pilot study. Endoscopy. 2010 Jul;42(7):564-70. doi: 10.1055/s-0030-1255537. Epub 2010 Jun 30.
citation: Kitano M, Kudo M, Yamao K, Takagi T, Sakamoto H, Komaki T, Kamata K, Imai H, Chiba Y, Okada M, Murakami T, Takeyama Y. Characterization of small solid tumors in the pancreas: the value of contrast-enhanced harmonic endoscopic ultrasonography. Am J Gastroenterol. 2012 Feb;107(2):303-10. doi: 10.1038/ajg.2011.354. Epub 2011 Oct 18.
citation: Saftoiu A, Vilmann P, Dietrich CF, Iglesias-Garcia J, Hocke M, Seicean A, Ignee A, Hassan H, Streba CT, Ioncica AM, Gheonea DI, Ciurea T. Quantitative contrast-enhanced harmonic EUS in differential diagnosis of focal pancreatic masses (with videos). Gastrointest Endosc. 2015 Jul;82(1):59-69. doi: 10.1016/j.gie.2014.11.040. Epub 2015 Mar 16.
citation: King KG, Gulati M, Malhi H, Hwang D, Gill IS, Cheng PM, Grant EG, Duddalwar VA. Quantitative assessment of solid renal masses by contrast-enhanced ultrasound with time-intensity curves: how we do it. Abdom Imaging. 2015 Oct;40(7):2461-71. doi: 10.1007/s00261-015-0468-y.