Clinical trial: NCT03219372
Section: Alternatives
Subsections: 4. Are There Benefits In Taking Part In The Study? If You Agree To Take Part In This Research Study, There May Or May Not Be Direct Medical Benefit To You.|6. Are There Any Other Options?

If you are randomized to receive pravastatin, the possible benefit of taking part in the research study is that the study drug may delay or prevent HCC recurrence. However, no benefit is guaranteed. If you are randomized to receive placebo, you should not expect to benefit from taking part in this research study. In either case, it's possible that your condition may remain unchanged or even get worse. We hope the information learned from this research study will benefit other individuals with HCC and cirrhosis in the future by helping us to learn whether pravastatin may delay or prevent HCC recurrence.

Your participation is voluntary so you have the right to decline to participate or to withdraw from this research study at any time without any penalty or loss of benefits to which you would be entitled outside of the study. Choosing not to participate will not affect the care you receive. If you decide not to take part in this study, you have other choices. For example:
- you may choose to be treated following the usual clinical approach - you may choose to take part in a different study, if one is available - you could decide not to be treated.  
The researcher will discuss these options and their risks and benefits with you.
Clinical trial: NCT03219372
Section: Confidentiality
Subsections: 7. Will My Information Be Kept Confidential?

We will do our best to make sure that the personal information collected as part of this study is kept private. However, we cannot guarantee total privacy. A copy of your research consent and authorization forms may be filed in your electronic medical record. Your personal information may be given out if required by law. If information from this study is published or presented at scientific meetings, your name and other identifiable personal information will not be used. Organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include: accrediting agencies, government and regulatory groups (such as Food and Drug Administration (FDA), Office for Human Research Protections (OHRP), etc.), safety monitors, companies that sponsor the study, CSMC coordinating center Staff for safety and quality monitoring, and authorized representatives of the sponsor. UCLA, NWU, UCSF, and EU participant data and specimens will be sent to CSMC in a coded manner. CSMC personnel will not have access to the key code; only the PIs and study staff from UCLA, NWU, UCSF, and EU will have access to the key code for participants at their institutions. A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This Website will not include information that can identify you. At most, the Website will include a summary of the results. You can search this Website at any time. As part of this research, it is necessary to restrict your right to access copies of health information created during your participation in your research while the research study is in progress. This restriction is necessary to maintain the blinding, in other words, it is important to the study outcomes that you not know into which treatment group you were assigned. Your right to access this information will be restored upon completion of the entire study if requested.
Clinical trial: NCT03219372
Section: Duration of Study Involvement
Subsections: How Long Will You Be In The Study

We think you will be actively participating in this study for about 12 months. The total time includes 6 study visits over 12 months. You will start the study drug (pravastatin or placebo) at the first study visit and will be required to take it daily over these 12 months. Study Visits will take between 1-3 hours to complete. We will make follow-up telephone calls to you 30, 60, and 90 days after completion of Study Visit 6 to assess symptoms and adverse events. If you receive a liver transplant before the end of this study (within or beyond the 12-month intervention period), we will obtain blood and liver tissue specimens from the liver that is removed at the time of transplantation. No additional visit will be required for these collections. Regardless of whether or not you receive a liver transplant, we would like to keep track of your medical condition for ten years and review your medical records periodically to see how you are doing. Checking on your condition every so often helps us look at long-term effects of the intervention.
Clinical trial: NCT03219372
Section: Participant's Rights
Subsections: Experimental Subject'S Bill Of Rights

In accordance with California Health and Safety Code 24172, any person who is required to consent to participate as a subject in a research study involving a medical experiment or who is requested to consent on behalf of another has the right to:
1. Be informed of the nature and purpose of the experiment. 2. Be given an explanation of the procedures to be followed in the medical experiment, and any drug or device to be utilized.  
3. Be given a description of any attendant discomforts and risks to the subject reasonably to be expected from the experiment.  
4. Be given an explanation of any benefits to the subject reasonably to be expected from the experiment, if applicable.  
5. Be given a disclosure of any appropriate alternative procedures, drugs or devices that might be advantageous to the subject, and their relative risks and benefits.  
6. Be informed of the avenues of medical treatment, if any, available to the subject after the experiment if complications should arise.  
7. Be given an opportunity to ask any questions concerning the experiment or the procedure involved.  
8. Be instructed that consent to participate in the medical experiment may be withdrawn at any time and the subject may discontinue participation in the medical experiment without prejudice.  
9. Be given a copy of any signed and dated written consent form used in relation to the experiment.  
10. Be given the opportunity to decide to consent or not to consent to a medical experiment without the intervention of any element of force, fraud, deceit, duress, coercion, or undue influence on the subject's decision.
Clinical trial: NCT03219372
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: 3. What Are The Possible Risks?|Risks Of Pravastatin|Unknown Risks|Alcohol Consumption|Reproductive And Lactation Risks|8. What If I Become Ill Or Injured Because Of Taking Part In This Study?

Risks of common medical procedures performed solely for research purposes are described in a table attached to the end of this consent form as Appendix B. Side effects and risks of standard of care procedures are not described in this consent form. This section describes the possible risks and/or discomforts we anticipate you could experience that are related to the study procedures.  
The study drug capsules (pravastatin and placebo) contain a small amount of lactose powder that is much less than the amount of lactose contained in a glass of milk. Mild abdominal issues (cramping, bloating, flatulence, diarrhea, nausea) are possible, but very rare with this small amount of lactose.

Pravastatin may affect how different parts of your body work, such as your liver and kidneys. You will have blood tests before and during the study to monitor your organ function. Your study doctor will let you know if changes occur that may affect your health. Women who are pregnant or may become pregnant should not use pravastatin. When taken during pregnancy, pravastatin may cause harm to a developing baby. If you are able to become pregnant, you will have a pregnancy test before the study start. Let your study doctor know immediately if you believe you might be pregnant. Other possible side effects of pravastatin are summarized in the table below. You will be asked to keep a diary during the study to record any side effects and symptoms you may be experiencing.  
| Occasional,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   |                                                                                                                                                                                                                                                                                                                          |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| some may be serious                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           |                                                                                                                                                                                                                                                                                                                          |
| (occurs in 4-20% of people)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   | Possible,                                                                                                                                                                                                                                                                                                                |
| some may be serious                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           |                                                                                                                                                                                                                                                                                                                          |
| (occurs in 1-3% of people)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    | Rare,                                                                                                                                                                                                                                                                                                                    |
| and serious                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   |                                                                                                                                                                                                                                                                                                                          |
| (occurs in less than 1% of people)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            |                                                                                                                                                                                                                                                                                                                          |
|  Diarrhea  Musculoskeletal pain  (Symptoms: Aching or  stiffness of the entire body,  twitching muscles,  sensation of "burning" in  your muscles, localized or  widespread pain)  Upper Respiratory Infection  (stuffy or runny nose,  sneezing, sore throat, or  cough)  Angina Pectoris  (uncomfortable pressure,  fullness, squeezing or pain  in the center of the chest)  Rash  Nausea/vomiting  Muscle Myalgia (pain)  Pharyngitis (Sore throat)  Rhinitis (Stuffy nose)  Cough  Flatulence (gas)  Fatigue |  Confusion, forgetfulness, or  memory problems  Dyspepsia/Heartburn   Abdominal Distension  (swelling of the abdomen either  caused by gas or fluid  collection)  Influenza  Dizziness  Allergic reaction including  swelling of the face, lips,  tongue, and/or throat that may  cause difficulty in breathing or |
| STOP HCC Recurrence Main Consent                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              |                                                                                                                                                                                                                                                                                                                          | Page 4 of 18  
|  Headache                                                                                                                                                                                                                                                           | swallowing   |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------|
|  Liver failure (symptoms:  weakness, fatigue, weight loss,  yellowing of the skin or eyes)  Rhabdomyolysis (a breakdown  of muscle tissue), a rare  condition that may cause  kidney damage (symptoms:  muscle pain, tenderness, or  weakness; dark colored urine) |              |  
Food and Medication Interactions Grapefruit and grapefruit juice may interact with pravastatin and lead to potentially dangerous effects. Do not consume grapefruit products (grapefruit, grapefruit juice, grapefruit seed extract, or dietary supplements containing grapefruit) during the intervention portion of this study. Pravastatin interacts with many other medications in ways that can increase or decrease the amount of medication in your blood. The interactions could result in increased levels that can be dangerous, or decreased levels so that drugs don't work. Please refer to the attached list of drugs (Appendix C) that must be avoided while you are participating in this study.

There also may be other side effects or risks that we cannot predict. Many side effects may go away shortly after the study medication or procedure is stopped. However, in some cases they may be serious, long-lasting, permanent, and/or fatal. Tell your study doctor if you notice or feel anything different so they can check if you may be having a side effect.

Pravastatin should be used with caution in patients who consume more than 5 drinks per day of alcohol as pravastatin may cause liver injury. We will monitor your liver function closely.

Taking part in this research study can affect an unborn baby. Therefore, you should not become pregnant while on this study. Women who are able to become pregnant will be required to have a pregnancy test before the study, and must agree to use adequate birth control (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Let your study doctor know immediately if you believe you might be pregnant. Women should not breastfeed a baby while on this study. Unknown Risks to the Developing Embryo or Fetus (an unborn baby) If you are pregnant, or become pregnant during participation in this research, the study drug might involve risks to an embryo or fetus, which are currently unknown. It is important that you contact the researcher immediately if you believe you might be pregnant.

Contact your researcher at once if you feel that you are ill or have been injured because of taking part in this study. If it is a medical emergency, call 911 or go to an emergency room. Promptly notify your researcher of your situation at the phone number listed on page 1 of this consent form. Who pays for my research related illness or injury? Cedars-Sinai has no plans to pay for costs associated with the treatment of research-related injury or illness. We will make every effort to seek reimbursement from your health plan. However, you will be responsible for any deductibles and co-payments required under your health plan and for any claims ultimately denied by your health plan. Financial assistance may be available under Cedars-Sinai's Charity Care Policy and Procedure. If you feel that you have had a research-related injury and need financial assistance, please contact the IRB Office at 310-423-3783.
Clinical trial: NCT03219372
Section: Procedures
Subsections: 2. What Will Happen During The Study?

This section provides a general overview of what will happen during your participation in this study. Information included below should be considered along with the flowchart of procedures attached as Appendix A. The flowchart shows a timeline for research-related or standard of care procedures that are involved in your participation in this study. **Research-related procedures** are those performed solely for the research. They would not be performed if you did not take part in the study. Standard of care (routine) procedures would be performed both as part of this study and if you do not participate in this study. A table describing common medical procedures done solely for the purposes of monitoring and assessing your condition during this study is attached as Appendix B to the end of this consent form. Standard of care procedures that will be repeated or done at greater frequency are listed in the flow chart, attached Appendix A.
Clinical trial: NCT03219372
Section: Purpose of Research
Subsections: 1. What Is The Purpose Of This Research Study?

Hepatocellular Carcinoma (HCC) is a major health concern in the United States, particularly among people with liver cirrhosis. Out of every 100 patients with liver cancer, only 18 will survive 5 years or more. While therapies targeting the liver are used in an effort to combat this disease, there is a high chance of HCC occurring again after these therapies. Statins are widely used drugs that lower cholesterol levels. Some studies have suggested that statins lower risk of HCC, but this possibility has not been studied thoroughly in a clinical trial. We are doing this study to examine the effects that pravastatin, a type of statin, has on the time it takes for HCC to occur again in patients with early stage HCC. We think that pravastatin in combination with therapies targeting the liver may delay or protect against HCC occurring again. You are being asked to take part in this research study because you have been diagnosed with an early stage HCC and have been treated with therapies targeting the liver. This research study is designed to study the investigational use of pravastatin. Pravastatin is approved by the U.S. Food and Drug Administration (FDA) to lower cholesterol and reduce the risk for heart attack, stroke, and chest pain in patients who have heart disease or at risk for heart disease. However, pravastatin is not approved by the FDA to delay or protect against HCC occurring again.  
The study will enroll up to 130 people in total. This study will be conducted and enroll patients at five different sites: CSMC (lead site and data and specimen coordinating center), NWU, UCLA, UCSF, and EU.
Clinical trial: NCT03219372
Section: Withdrawal from Study
Subsections: 5. Why Would My Participation Be Stopped?

Your participation in this study may be stopped at any time by the researcher or the sponsor without your consent for any reason, including: - The study is stopped or suspended; - Funding for the study is reduced, stopped or withdrawn; - If treating physician judges that discontinuation in the study is in your best interest; - You do not consent to continue in the study after being told of changes in the research that may affect you;
- You do not follow the study procedures; - You demonstrate recurrence of HCC (unless continued treatment with study drug is deemed appropriate at the discretion of the investigator);
- You experience toxicity that makes continuation of the drug unsafe; - You become pregnant; - You develop a second malignancy (except for basal cell carcinoma or squamous cell carcinoma of the skin) that requires treatment, which would interfere with this study; You may choose (or you may be required) to withdraw from certain parts of the study, but invited to continue with other parts. For example, you might stop taking a study drug, but continue with followup visits or allow us to continue to collect data from your medical records. Separate written consent will be requested if your continued participation will involve procedures not described in this consent form.