Clinical trial: NCT02764801
Section: Confidentiality
Subsections: 155 How Will Privacy And Confidentiality (Identity) Be Protected?

156 Federal regulations require that certain information about individuals be kept confidential. This 157 information is called "protected health information" (PHI). PHI includes information that 158 identifies an individual personally such as name, address and social security number, or any 159 medical or mental health record, or test result, that may have this sort of information on it. The 160 laws state that people may see and review their medical records at any time. However, in a 161 research study, people may not see the study results or other data about the study until after the 162 research is completed unless the study doctor decides otherwise. 163 164 PI:
Sponsor: NIH
Abbreviated Title: CEUS of HCC
165 The following individuals or entities may have access to your PHI and by law must protect it.  
166 These include investigators listed on this consent form and other personnel of Thomas Jefferson 167 University, Jefferson University Physicians, Thomas Jefferson University Hospitals, Inc. (add the 168 Rothman Institute if applicable) involved in this specific study, the University's Office of Human 169 Research and the Institutional Review Board (IRB), and your health insurance company (if 170 necessary for billing for standard medical care). 171 172 PHI collected during this study may also be shared with the following entities that, while not 173 obligated by law to protect PHI, will protect it to the best of their ability:
174  NIH which is providing funds to Thomas Jefferson University/Jefferson Health to 175 conduct this research 176  The Food and Drug Administration (FDA)
177  Dr. Robert Den, the medical monitor for the study, who will review medical records if 178 any unexpected side effects occur.  
179  Research Monitors hired by the sponsor to oversee the study and review medical records 180 to ensure study-related information is correct, 181  With any person or agency required by law.  
182 183 The following information will be provided to the study sponsor and other entities noted above: 184 185 Study data for analysis: *The ultrasound images, MRI or CT images and reports, outcome,* 186 *pregnancy test (if applicable), and medical/surgical history to determine whether CEUS can access* 187 *whether TACE was successful and to see whether you meet the eligibility criteria.* 188 189 **Demographic data:** Your race and ethnicity to track enrollment statistics 190 191 **Other:** None 192 193 If you develop an illness or injury during the course of participation in this study, other PHI 194 about treating and following the condition may be generated and disclosed as it relates to this 195 study. 196 197 PHI collected as part of this research may be used indefinitely. 198 199 You may quit the study and revoke permission to use and share PHI at any time by contacting the 200 principal investigator, in writing, at: John Eisenbrey, PhD Thomas Jefferson University, 132 South 10th Street, 7th 201 Floor, Philadelphia, PA 19107. Further collection of PHI will be stopped on 202 those who quit the study, but PHI that has already been collected may still be used. 203 204 205 206 Version Date: 04/28/2020 Version Number: 3.2 Page 6 of 9 PI:
Sponsor: NIH
Abbreviated Title: CEUS of HCC
207 The results of clinical tests and procedures performed as part of this research may be included in 208 your medical records. The information from this study may be published in scientific journals or 209 presented at scientific meetings but no one will be personally identified in these publications and 210 presentations. 211 212 A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 213 by U.S. Law. This Web site will not include information that can identify you. At most, the Web 214 site will include a summary of the results. You can search this Web site at any time. 215 216 What happens in case of injury **as a result of being in this study?** In the event of a research217 related injury, necessary and available medical care (including hospitalization) will be provided.  
218 A research-related injury is a physical injury or illness that is directly caused by any procedure or 219 treatment used in this study that is different from the treatment you would receive if not 220 participating in a research study. If physical injury occurs due to any drug/substance or procedure 221 properly given under the plan for this study, medical expenses for treating the injury will be 222 billed to your insurance carrier. You should be aware that some costs may not be covered by 223 insurance and may become your responsibility. There is no plan to provide compensation for loss 224 of wages, lost time from work, personal discomfort, or for injuries or problems related to your 225 underlying medical condition(s). 226 227 If you have questions about the sponsor's agreement regarding payment for a research-related 228 injury please discuss with the study doctor. 229 230 If a bill related to a research-related injury is received that seems wrong, please discuss it with 231 the study doctor or research coordinator. 232 233 Is there payment **for being in this study?** 234 235 There is a payment $100/33.00 per/scan for participating in this study. 236 237 238 **Disclosure of Financial Interest** 239 240 The sponsor of this clinical study, NIH, is paying Thomas Jefferson University to conduct this 241 study. 242 243 Version Date: 04/28/2020 Version Number: 3.2 Page 7 of 9 PI:
Sponsor: NIH
Abbreviated Title: CEUS of HCC
Clinical trial: NCT02764801
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: 117 What Are The Side Effects And Other Risks Or Discomforts Involved?

118 There are no risks from the use of diagnostic ultrasound. 119 120 The majority of adverse events from Definity are temporary and mild in severity. Of the 121 reported adverse reactions following the use of Definity the most frequently reported were 122 headache (2.3%), back and renal pain (2.1%), sudden increase in blood flow to face (1.1%) and 123 nausea (1.0%). Hypersensitivity reactions (severe allergic reaction that may include abnormal 124 redness of skin, slow heart rate, low blood pressure or, rarely, difficulty breathing) to Definity 125 may occur, although rare. 126 127 PI:
Sponsor: NIH
Abbreviated Title: CEUS of HCC
128 The company that makes Definity has indicated that there is the potential of serious heart and 129 lung reactions occurring uncommonly during or following administration of Definity. The risk is 130 only in patients with heart and lung problems. You will be screened for any of these conditions 131 and if it is found that you have any of these conditions, you will not be able to participate in this 132 study. 133 134 The use of an intravenous needle and the fluids given through the needle may cause minor 135 discomfort, bleeding under the skin (bruise), and possible infection at the site of needle insertion. 136 137 The only other risk is the possible breach of confidentiality. The investigators will take every 138 precaution to ensure patient confidentiality will be maintained. 139 140 You should tell or call the study doctor as soon as possible at 215-503-5188 if, during the course 141 of this study, you develop any of these side effects or symptoms. The study doctor has told you 142 that if your condition worsens, if side effects become very severe, or if it turns out that being in 143 this study is not in your best interest, you will be taken out of the study. If you have any side 144 effects or symptoms after normal business hours go the nearest emergency room. If questions 145 come up about side effects, ask the study doctor or staff at any time during or after the study. 146
Clinical trial: NCT02764801
Section: Purpose of Research
Subsections: 43 What Is The Purpose Of This Study?

44 You are being invited to participate in this study because you are scheduled to have a type of 45 treatment for a mass on your liver called transarterial chemoembolization (TACE). TACE 46 involves injecting drugs that treat cancer with small beads or oil directly into a blood vessel that 47 supplies blood to the mass. The beads or oil block the blood flow to the tumor, as well as deliver 48 cancer drugs directly to the mass. Normally, about 1 month after the TACE procedure, you will 49 be scheduled for an MRI or CT to determine whether the TACE procedure successfully treated 50 the liver mass. The MRI or CT involves the use of a dye that can sometimes cause side effects. 51 The purpose of this study is to determine whether another type of imaging test with ultrasound 52 imaging and a contrast agent that does not involve dye can be used to determine whether the 53 TACE procedure treated the liver mass, and if this test can determine the treatment effectiveness 54 earlier. If this is successful, it is possible that people can have this ultrasound imaging exam 55 earlier and rather that the MRI with dye. 56 57 This is a Phase 2 study. Phase 2 research studies are done to get further information on safety, 58 dosage, and side effects and to collect preliminary information about how well a drug works 59 (often referred to as efficacy). Phase 2 studies usually have very strict rules about who may and 60 who may not be in the study. Phase 2 studies may compare a new drug to a placebo (inactive 61 substance) or to a known treatment. 62 63 You are being asked to participate in this study because you are scheduled for TACE of a liver 64 mass. The purpose of this study is to compare the results of ultrasound imaging with contrast 65 (CEUS) at 1 -2 weeks and 1 month after your TACE with that of the MRI or CT that your doctor 66 has scheduled to receive 1 month after your TACE procedure. 67 68 The ultrasound contrast agent being used in this study is Definity. Definity is an ultrasound 69 contrast agent that contains tiny gas bubbles about the same size as red blood cells that reflect 70 ultrasound (sound waves). The microbubbles in Definity stay in areas of blood vessels and 71 reflect sound waves and show where there is blood flow. Definity is FDA-approved in the United 72 States for use with echocardiography (ultrasound of the heart). 73 74 For this study, the CEUS imaging will be performed on an FDA-approved ultrasound system, the 75 Logiq E9. To acquire and process the CEUS images, the ultrasound system software has been 76 modified to detect Definity. This only changes the way in which the images are processed by the 77 ultrasound system. It does not change the strength or the composition of the sound waves being 78 transmitted to your body. 79 80 How many individuals will participate in the study and how long will **the study last?**
81 210 patients will participate nationally. We hope to enroll **up 100** patients at Jefferson. Each 82 participant will be in the study for about 1 month. The entire study will take about 5 years to 83 complete. 84 85 PI:
Sponsor: NIH
Abbreviated Title: CEUS of HCC
86 What will happen **during the study?**
876 Individual participation in this trial will be limited to three 60 minute exams including the CEUS
887 exam and monitoring you after the CEUS. The first examination will be on the morning of your 898 scheduled TACE procedure prior to the procedure, the second will be 1-2 weeks after the TACE 9089 procedure, and the third will be on the day you come in for your MR imaging at 1 month after the 910 TACE and will be performed prior to the MR imaging. 92 93 For all 3 research visits, you will be asked to review your medical and surgical history, 94 any current medications you are taking, and any known drug allergies or intolerances. If you are 95 a woman of childbearing potential, you will have a urine pregnancy test (the results of which will 96 be made available to you prior to the start of the research study). For the CEUS, an intravenous 97 catheter (small plastic tube) will be placed in a vein in your arm. You will be asked to lay on 98 your back on an examination table. Ultrasound gel, to assist in the ultrasound imaging, will be 99 applied to the area of your abdomen over your liver. An ultrasound probe will be moved across 100 the area over your liver to obtain the ultrasound images. 10194 102 A standard (without contrast) ultrasound examination of your liver will be performed to locate 103 the liver mass and obtain information about the size, shape and ultrasound characteristics. After 104 the standard exam is complete, you will receive an injection (approximately 1 teaspoon)
105 of Definity through the catheter in your arm, followed by an injection of saline (salt water). You 106 105 will then have continuous CEUS imaging for 1 minute. If the Definity is not seen on the CEUS, 107 106 you may receive a second injection of Definity through the catheter in your arm, followed by 108 107 another injection of saline (salt water). This will be followed by CEUS imaging. The CEUS 109 108 imaging will not feel any different than the standard imaging. 110 111 You will be monitored during the entire procedure and for 30 minutes after the final injection of 112 Definity. 113 114 The CEUS findings will be compared to the MRI or CT results at 1 month. Additionally, the 115 CEUS results will be compared to the long term outcome of your TACE treatment.  
116
Clinical trial: NCT02764801
Section: Withdrawal from Study
Subsections: 268 Can I Be Removed From The Study Or Quit The Study?

269 270 Your decision to participate in this research study is entirely voluntary. You have been told what 271 being in this study will involve, including the possible risks and benefits. 272 273 Your participation in this research project may be terminated by the study doctor or study 274 sponsor without your consent for any reason that he/she feels is appropriate. 275 You may refuse to participate in this investigation or withdraw consent and quit this study 276 without penalty and without affecting the ability to receive medical care at Thomas Jefferson 277 University/the Rothman Institute. 278 279 If you withdraw from this study, you may continue treatment with your Jefferson doctor, or you 280 may seek treatment from another doctor of your choice. 281 282 Version Date: 04/28/2020 Version Number: 3.2 Page 8 of 9 PI:
Sponsor: NIH
Abbreviated Title: CEUS of HCC  
283 **CONTACT INFORMATION** 284 285 **If you are having a medical emergency, call 911 or go directly to an emergency room. You** 286 should let emergency personnel or providers know that **you are participating in this study.** 287  
Telephone number for questions about your rights as a research participant  
| Telephone number for  questions about your rights as  a research participant   | The Jefferson Institutional                                                                                      | 215-503-8966   |
|--------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------|----------------|
| Review Board                                                                   |                                                                                                                  |                |
| For questions, concerns or  complaints about the research,  or if you suspect a researchrelated injury                                                                                | The Principal Investigator, Dr. John Eisenbrey, PhD or any co-investigator listed at  the beginning of this form | 215-503-5188   |
| If you have difficulty                                                         | Call the Jefferson Office of                                                                                     | 215-503-0203   |
| contacting the study staff                                                     | Human Research                                                                                                   |                |  
288 289 290 If you want more information about the Jefferson Institutional Review Board or Jefferson's 291 Human Research Protection Program, please visit our website at 292 http://www.jefferson.edu/human_research/irb/index.cfm. 293 294 295 296 **Subject Communications** 297 298 Do you wish to communicate with the study staff by e-mail? YES _____ NO _____ 299 300 If you checked yes, please print your e-mail address on the line below. 301 302 303 304 **RISKS:** E-mail correspondence is not always secure and there is a risk of loss of confidentiality.  
305 To help protect against loss of confidentiality, all e-mail that originates from Jefferson University 306 or Jefferson Hospital employees using Jefferson University or Jefferson Hospital e-mail 307 addresses is encrypted. That means, unless you have allowed others to have access to your e308 mail, only you will see the e-mail.  
309 310 YOU SHOULD **NEVER** USE E-MAIL TO REPORT A SUSPECTED ADVERSE EVENT OR
311 ANY OTHER MEDICAL PROBLEM. THESE SHOULD BE REPORTED BY TELEPHONE. 312 313 314 315 PI:
Sponsor: NIH
Abbreviated Title: CEUS of HCC
Version Date: 04/28/2020  
  
  
Version Number: 3.2 Page 9 of 9 316 **Non-Waiver of Legal Rights Statement**  
  
  
317 318  By your agreement to participate **in this study, and by signing this consent form, you**
319 are not waiving any of your **legal rights.**
320  In order to be in this research study, you must sign this consent **form.**
321  **You affirm that you have read all pages of this consent form. You have been told** 322 **that you will receive a copy.** 323 324 **SIGNATURES** 325 326 ______________________ ______________________ __________ 327 Your Name Your Signature Date 328 329 330 ______________________ ______________________ __________ 331 Name of **Person Conducting** Signature of **Person Conducting** Date 332 **Consent Interview Consent Interview**
333 334 The invest**igator's** signature certifies that s/he personally provided the study participant 335 with a description of the study, study procedures, risks, benefits and alternatives to 336 participation. 337 338 339 ______________________ ______________________ __________
340 Name of **Investigator** Signature of **Investigator** Date 341 **or Co-Investigator or Co-Investigator**
342 343 344 **Copy of Signed and Dated Consent Form Given to the Subject/Parent/LAR**
345 346 ***