Clinical Trials

The purpose of this study is to find out whether restoring blood flow to all blocked or narrowed arteries with a percutaneous coronary intervention (PCI, a procedure that opens the blockage or widens the narrowed artery with a stent) is better than using medications alone after a transcatheter aortic valve replacement (TAVR).

To qualify for the study you must have:

• Severe symptomatic aortic valve stenosis and qualify for TAVR procedure.
• Have a blocked or narrowed coronary artery with 70% or greater narrowing.

Once you have gone through the TAVR procedure, you will be randomized to opening the narrowed arteries or being treated with optimal medical therapy only. You will be followed at 1 month, 6 months and yearly for five years.

Study Team: Dr. Mansoor Qureshi. Nora Marchelletta RN, BSN

The study is evaluating the safety and effectiveness of a new therapy, INCLISIRAN, which lowers LDL-cholesterol (bad cholesterol) in patients who have recently had a heart attack. The study is looking at the changes in your LDL levels. INCLISIRAN, has been shown in previous studies to lower LDL-cholesterol by blocking the production of a protein call PCSK9. This protein reduces the liver’s natural ability to remove LDL-cholesterol form the blood.

To qualify for the study you must have:

• Been recently hospitalized with a heart condition.
• Currently taking a cholesterol lowering medication or have been told you are intolerant to statins.

If you decide to participate, it is very important that you continue to take your cholesterol lowering medication. One half of the participants in the study will receive INCLISIRAN and the other half will not receive a study treatment but will be monitored. You will be in the study for one year and seen in the office five times during this time period. Blood samples, ECG’s, vital signs and questionnaires will be completed.

Study Team: Dr. Marlo Leonen. Kristina Wippler, RN, BSN.

The study is being done to determine if a medication called INCLISIRAN can safely and effectively prevent cardiovascular events in the future (such as heart attacks, strokes, cardiovascular-related death, or procedures to improve blood flows (also called “revascularization”)) by lowering LDL-cholesterol in the blood.

To qualify for the study, you must:

• Be at risk for having a cardiovascular event
• Have a high LDL-cholesterol

If you decide to participate, there will be certain tests/questionnaires you must complete to find out if you meet the requirements to be in the study. One half of the participants in the study will receive INCLISIRAN and the other half will not receive the study treatment but will be monitored. You will most likely be in the study for approximately 6 years. During this time, you will be seen in the office 4 times in the first year. After the first year, you will be seen every 6 months (twice a year). Blood samples, vital signs, and questionnaires will be completed during clinic visits.

Study Team: Ahmad Mizyed, MD. Bozhena Stakh, RN.

The study is being done to determine if a medication call INCLISIRAN, taken in addition to statin medication in people with established cardiovascular disease, can safely and effectively lower the risk of cardiovascular events in the future (i.e. heart attacks, strokes, and cardiovascular-related deaths)

To qualify for the study, you must:

• Have been diagnosed with a cardiovascular disease
• Be currently taking a statin medication

If you decide to participate, it is very important that you continue to take your statin medication. One half of the participants in the study will receive INCLISIRAN and the other half will not receive the study treatment but will be monitored. You will most likely be in the study for approximately 3-6 years depending on when you enter the study. During this time, you will be seen in the office 4 or 7 times in the first year. After the first year, you will be seen every 6 months. Blood samples, vital signs, and questionnaires will be completed.

Study Team: Ahmad Mizyed, MD. Sarah Whitsett, RN.

This study is being done to compare the effects of a study drug called obicetrapib vs. placebo to find out if obicetrapib is helpful for treating atherosclerotic cardiovascular disease and reducing the risk of major cardiovascular events when taken with existing medication.

To qualify for the study, you must:

• Have been diagnosed with atherosclerotic cardiovascular disease (ASCVD).
• Have a high level of Low-Density Lipoprotein Cholesterol (LDL-C) in your blood.

If you are eligible and decide to participate in the study, you will be randomly assigned in a 1:1 fashion (50% chance) to receive either obicetrapib or placebo. Study procedures will be performed during four stages of this study: Screening, Study Treatment Period, End of Study Treatment (or Early Termination) and Follow-up Period.

This is an event-driven study, which means that it will complete after a certain number of cardiovascular events have occurred in the whole population of study participants, but no sooner than 32 months after you start the study. Therefore, your participation in this study will last at least 32 months and include around 14 study visits. Blood samples and ECGs will be completed during certain study visits.

Study Team: Ahmad Mizyed, MD. Kristy Wippler, RN, BSN.

The study is being done to determine whether Intensive Cardiac Rehabilitation (ICR) provides more health benefits and lower costs compared to Conventional Cardiac Rehabilitation (CCR).

To qualify for the study, you must:

• Have had a cardiac event
• Have been referred to cardiac rehabilitation

If you decide to participate and meet the eligibility requirements, you will be placed into one of three different study groups. You have an equal chance of being randomized into one of the three study groups: Convention Cardiac Rehabilitation (CCR), Intensive Cardiac Rehabilitation (ICR), Intensive Cardiac Rehabilitation (ICR) Plus Food. You will complete questionnaires, have blood draws three times, and have a buccal (cheek) swabbing performed two times during the study. You will be involved in this research study for approximately 2 years.

Study Team: Frank Smith, MD. Autumn Howe, RN.

The study is being done to see if ziltivekimab can be used to treat people who were admitted to hospital because of a heart attack.

To qualify for the study:

• You were admitted to the hospital because of a heart attack
• You have previously been diagnosed with conditions such as heart disease, stroke (blocked blood supply to the brain), reduced kidney function or diabetes (a disease that effects how well the body can control sugar levels in the blood).

If you decide to participate, you will be asked to come to 10 visits at the clinic (2 of them when you are in the hospital at the start) and have 3 phone calls with the study doctor/staff. There are 2 study medicines: Ziltivekimab and Placebo. You will only take 1 of these medicines. Ziltivekimab is not yet approved in any country or region in the world. It is a new medicine that doctors cannot prescribe.

Study Team: David Sutter, MD. Megan Thompson, RN

This study will test whether the drug dapagliflozin is safe and has beneficial effects when added to conventional heart failure therapy in patients who have been admitted to the hospital for acute heart failure and whose heart pumping function is weakened.

To qualify for the study you must have:

• Been hospitalized with a heart failure.
• A reduced pumping ability of your heart muscle (ejection fraction less than or equal to 45%).

If you are eligible to take part in the study, you will be randomized to receive either dapagliflozin tablet or placebo tablet. You will have a 50% chance of receiving dapagliflozin or 50% chance of receiving placebo. You will not know what drug you are receiving.

The study medication will start while you are in the hospital. You will be seen at 1 week, 1 month and 2 months in the research office.

Study Team: Dr. Marlo Leonen. Kristy Wippler, RN, BSN.

The study is being done to determine if a medication called ziltivekimab can be used to treat people living with heart failure and inflammation.

To qualify for the study, you must:

• Be diagnosed with heart failure and have limitations in your daily life because of the disease
• Have inflammation in the body

If you decide to participate, you will either receive ziltivekimab (the new medicine being tested) or placebo (an inactive dummy medicine). The study medicine you get is decided by chance (like flipping a coin). You will get your study medicine as an injection. You will need to inject the study medicine into the skinfold in your stomach, thigh, or upper arm once every month. The study is expected to last for up to 4 years. During this time, you may be asked to come to clinic for up to 20 visits. A study app (on your personal phone or provided study phone) will be used to record and share information about all your injections. The study app will also be used to complete questionnaires. Some clinic visits may include blood draws and electrocardiograms.

Study Team: Mansoor Qureshi, MD. Nora Marchelletta, RN.

We are doing this study to learn more about how effective, safe, and tolerable an experimental drug called balcinrenone is when used in combination with dapagliflozin for treating patients with heart failure and impaired kidney function and also to better understand the studied disease and associated health problems.

To qualify for the study:

• you have heart failure and had a recent worsening of your symptoms that required hospitalization or an urgent out-patient visit
• You have impairment of your kidney function

If you decide to participate, you will be in the study on average 22 months, but you may be in the study shorter or longer, depending when you enter the study. There will be a Screening Period (to determine eligibility), a Treatment Period (where you will be randomly assigned to a study drug), and Follow-up Period (which will occur within 4 weeks after the last dose in the Treatment Period).

Study Team: Marlo Leonen, MD. Nora Marchelletta, RN

The purpose of this clinical research study is to look at the effectiveness, safety, and tolerance of combining the study drug called BI 690517 with empagliflozin (empa) in participants diagnosed with heart failure (HF). In this study, the potential new treatment option is compared with a treatment with empa and placebo.

To qualify for the study:

• you have a confirmed diagnosis of chronic heart failure (HF)
• You are at least 18 years of age

If you decide to participate, you will be in this study for up to about 3.5 years. The study involves approximately 18 visits to the study site. The study consists of 3 periods: Screening Period (up to 3 weeks to determine your eligibility), Study Treatment Period (at least 1.5 years and up to about 3.5 years), and the Follow-up Period (1-2 weeks).

Study Team: Marlo Leonen, MD. Meghan Stelzer, RN

The purpose of this study is to find out if using mononuclear cells (MNCs) from your own bone marrow will improve your symptoms of heart failure by showing improvement in the 6-minute walk test.

To qualify for the study you must have:

• Had a previous heart attack.
• Been told that you have heart failure.

If you decide to participate, you will go through a screening period to find out if you qualify for the study. Qualifying patients will be scheduled for the procedure and randomized (assigned by chance) into one of 2 groups. 60% receive the treatment and 40% will be in the control group and will not receive the MNC injections. You will not know what group you are in. You will be seen at 1, 3, 6, 9 and 12 months with yearly visits for 2 years.

Study Team: Dr. Zakir Sahul. Nora Marchelletta, RN, BSN.

This study is being done to assess whether remote monitoring of vital signs (blood pressure, pulse, respiratory rate, oxygen levels, weight) and use of a cloud-based clinical support tool (mobile study application or “app”) can improve prescribing and dosage increases of medications used in the treatment of heart failure.

To qualify for the study you must have:

• Have been diagnosed with heart failure.
• Have a reduced pumping ability of your heart muscle (ejection fraction less than or equal to 40%).

If you are eligible and decide to participate in the study, you will have a 50% chance of being enrolled in the intervention group or the control group (which involves standard treatment of your heart failure). Participants randomized to the intervention group will be remotely monitored for 90 days. A mobile study application (“app”) will be utilized to manage your heart failure medications based on standard clinical guidelines. You will be in the study for approximately 180 days.

Study Team: Ahmad Mizyed, MD. Nora Marchelletta, RN.

This study is being done to test if closing off the heart’s left atrial appendage (LAA) with a surgical device, known as the AtriClip, reduces stroke occurrence in patients who do not have atrial fibrillation (AF) but who have one or more risk factors for developing AF in the next 5 years.

To qualify for the study, you must:

• Be scheduled to have heart surgery.
• One or more risk factors for developing AF in the next 5 years.

f you decide to participate, you will undergo certain study assessments (blood draws, physical exams) to determine your eligibility for the study. If your doctor determines that you qualify, your involvement will last at least 5 years and possibly up to 10 years. Eligible participants will be randomly assigned in one of two treatment groups: Group 1 (LAA closure using AtriClip during heart surgery) and Group 2 (no LAA closure during heart surgery). After the procedure, a series of follow-up visits will occur to monitor your health. You will continue to receive study follow-up care unless you decide to withdraw from the study, or the sponsor stops the study.

Study Team: Robert Lyons, MD. Megan Thompson, RN.

This study is being done to determine whether CCM therapy delivered by the Optimizer System can improve outcomes in patients with heart failure.

To qualify for the study, you must:

• Be diagnosed with symptomatic heart failure
• Have a recent heart failure hospitalization or urgent heart failure visit requiring IV therapy

If you qualify and decide to participate in this study, you will undergo implantation of the OPTIMIZER® device. You will then be randomly placed into one of two study groups. The decision about which group you will be in will be based on chance, like flipping a coin. Neither you nor your doctor will know which group you have been assigned.

1. ACTIVE GROUP: You will have a 2/3 chance of having CCM® turned ON
2. CONTROL GROUP: You will have a 1/3 chance of having CCM® turned OFF

After the 18-month blinded phase of the trial is completed, you will begin the unblinded phase of the trial. If you were in the CONTROL group with CCM® OFF, you will have CCM® therapy turned ON at this time so all devices will have CCM® turned ON after the blinded phase. The long-term follow-up period is required so that we can continue to monitor your device and safety events while enrollment and follow-up is completed for all participants and the FDA has made a decision regarding the safety and efficacy of CCM® therapy in patients with HF(40-60)pEF. This long-term follow-up period could last more than 5 years, depending on when you are enrolled.

Study Team: Ahmad Mizyed, MD. Autumn Howe, RN.

This study is being done to evaluate the safety of long-term use of the Optimizer System and CCM therapy for patients who have already made the decision to have the Optimizer system implanted. The post approval study (PAS) will also evaluate the effects of CCM therapy on your quality of life and heart failure symptoms, as well as your heart’s ability to pump effectively and some potential blood related chemical changes.

To qualify for the study, you must:

• Be diagnosed with symptomatic heart failure
• Have a doctor believe you may benefit from a new FDA-approved heart failure therapy called cardiac contractility modulation (CCM therapy)

If you decide to participate, most of the procedures and assessments performed in this study will be no different than if you were to receive the Optimizer System without participating in this study. In some cases, results from assessments already recorded in your medical record may be used and for others, standard of care assessments shall be conducted. Some procedures and assessments will be performed for study purposes only (questionnaires, possible blood draws, ECGs, and echocardiograms). You will be in the study for approximately 3 years or until no further information is required for this study.

Study Team: Jihn Han, MD. Autumn Howe, RN.

This study is being done to determine if early study treatment with the medicine, dronedarone, is more effective than usual care alone for the prevention of unplanned cardiovascular hospitalization (such as hospitalization for heart failure, atrial fibrillation, stroke, heart attack, or death from any cause) in patients presenting to the hospital with first-detected atrial fibrillation (AFib).

To qualify for the study you must have:

• Have first-detected AFib (defined as AFib diagnosed in the previous 60 days).
• Have electrocardiographic documentation of atrial fibrillation.

If you are eligible and decide to participate in the study, you will be randomized 1:1 (50% chance) to receive either the study intervention (dronedarone plus usual care for atrial fibrillation), or usual care alone, without dronedarone.

You will be in the study for approximately 12 months with follow-up visits occurring at 6 months and 12 months.

Study Team: Andrew Hughey, MD

The goal of this study is to see if a new way of giving blood thinner medications after placement of the WATCHMAN FLX Pro device is safe and effective. This study will compare three different medication regimens used after the WATCHMAN FLX Pro device is inserted into your LAA.

The first regimen involves a group of blood thinners called non-vitamin K antagonist oral anticoagulants (abbreviated “NOACs”). The NOACs used in this study are apixaban (Eliquis®) or rivaroxaban (Xarelto®). Both are approved by the FDA but for the purposes of this study are given at lower doses than usual. Because they are given at lower doses than currently approved by the FDA, this makes this new NOAC regimen investigational.

The second regimen is the familiar antiplatelet medication aspirin, given alone (i.e., without other blood thinners) in the usual doses. Like other antiplatelet medications, aspirin is used to make the small components of your blood, called platelets, less “sticky” so they don’t clump together to form clots. Aspirin is currently approved by the FDA but only if given together with another blood thinner during the first six months after the procedure. However, for the purposes of this study, it will be given alone for the entire 12 months, which also makes this regimen investigational.

The third regimen is the standard FDA-approved combination of two antiplatelet medications, aspirin and clopidogrel (Plavix^®), given together. This is what is known as dual-antiplatelet therapy (DAPT).

Eliquis® is a registered trademark of Bristol-Myers Squibb Company, Xarelto® is a registered trademark of Janssen Pharmaceuticals Companies and Plavix® is a registered trademark of Sanofi.

To qualify for the study:

• You have a heart condition called atrial fibrillation (AFib)
• You are eligible for placement of a WATCHMAN FLX Pro implant device

If you are eligible for this study, your participation will last about 12-months. The study visits will consist of the Baseline Visit (confirm eligibility), Device Implant Procedure, Randomization (There are two “test” groups: (1) aspirin alone and (2) low-dose NOAC, and one “control” group (DAPT). Neither you nor your study doctor can choose your group.), and the in-person Follow-up visits.

Study Team: Jihn Han, MD. Nora Marchelletta, RN

It is studying if it is safe and effective to stop blood thinning medicine during times when the heart rhythm is normal. It is a randomized/comparison study. Participants in the standard of care group will be asked to stay on their regular blood thinner and will complete periodic surveys on their study app. Participants in the intervention group will receive an Apple Watch with study specific software that can detect signs of Afib and will be on time limited blood thinner use based on the Apple Watch monitoring.

To qualify for the study:

• Be between the ages of 22-85 years old
• Have a history of Afib
• On a blood thinner (not Coumadin/warfarin)
• Have an iPhone

Study Doctor: Mohammad-Ali Jazayeri, MD. Autumn Howe, RN

The purpose of the study is to find out how effective and safe CSL112 is at reducing the risk of dying from heart related events, having another heart attack, or having a stroke. Studies have shown that a protein in the body called apolipoprotein A-I (ApoA-I) may help to remove excess cholesterol from the arteries. CSL112 resembles HDL, which is sometimes better known as the ‘good cholesterol’.

To qualify for the study you must have:

• Been hospitalized with a recent heart attack
• Blockages or narrowing in more than one blood vessel in your heart.

If you are eligible to take part in the study, you will be randomized to receive either the CSL 112 or placebo. You will have a 50/50 chance of receiving either CSL112 or placebo.

The study drug will be given by intravenous (IV) infusion over 2 hours. You will receive up to four (4) infusions of study drug weekly for 4 weeks. All 4 infusions should be administered within 30 days of receiving your first infusion. Additional study visits will occur throughout the next year to assess for any new health problems, side effects, or changes in your medical conditions.

Study Team: Dr. David Sutter. Megan Thompson, RN, BSN.

The purpose of this study is to look at the effectiveness of the implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy pacemaker/defibrillator (CRT-D) devices in treating life threatening fast heart rhythm disorders and preventing death in the patients with heart failure due to non-ischemic (not due to coronary artery disease) cardiomyopathy.

To qualify for the study you must have:

• Heart failure due to non-ischemic cardiomyopathy.
• Been told you need or currently have an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy pacemaker/defibrillator (CRT-D) device to prevent sudden death.

If you decide to participate, the study doctor will determine if you qualify for the study. You will be scheduled for the implant procedure. The follow up is in office yearly for 3 years. You will also have home monitoring follow up visits at 6, 18 and 30 months.

Study Team: Dr. Srinivas Hebsur. Autumn Howe, RN, BSN.

The purpose of the study is to understand the value of ATP (anti-tachycardia pacing) in patients who have not yet received a shock from their defibrillator (primary prevention patients). ICD’s or defibrillators are implanted in certain patients who are at an increased risk of sudden cardiac death from fast and life threatening heart rhythm disorders. This study is to see if certain programing by ATP will reduce the number of shocks received and improve survival in such patients.

To qualify for the study you must have:

• Been implanted with an ICD (implantable cardioverter defibrillator) for the treatment of a potentially fast or life-threatening heart rhythm disorder.
• Meet the guidelines for primary prevention.

If you decide to participate, you will be randomized into one of two groups. Group one will have the ICD programed to deliver ATP treatment first and then only deliver a shock if needed. Group two will have their device deliver a shock only without ATP. Your follow up visits will be in the office yearly and your device will be checked every 6 months for up to five years.

Study Team: Dr. Jihn Han. Autumn Howe, RN, BSN.

The purpose of this study is to compare the efficacy (how well it works) and safety of the Firehawk stent to other FDA approved drug eluting heart stents (DES). The drug eluting stent is a special coated stent that releases a drug which helps prevent blockages from coming back.

To qualify for the study:

• Your physician has determined that you may need to receive a stent in one or more arteries in your heart.
• Ejection Fraction (pumping function of the heart) greater than 30%.

If you qualify, you will be randomized to one of two groups. One group will receive the Firehawk stent and the other group will receive the currently FDA approved drug eluting stent. The study team will call you at 30 days, 6 months, 2, 3, 4, and five years. You will be seen in the office at one year.

Study Team: Dr. Zakir Sahul. Megan Thompson RN, BSN

The purpose of the study is to determine at what red blood cell count patients should be given a transfusion in order to lower the risk of death, heart attacks and other health problems.

To qualify for the study you must have:

• Been hospitalized with a recent heart attack.
• A red blood cell count of less than 10g/dl.
• Be willing to accept a blood transfusion

If you decide to participate, you will be placed into one of 2 different study groups. The decision of which group is based on chance like flipping a coin. One group will receive blood transfusion immediately and the other group will not receive a blood transfusion unless the red blood count drops below 8g/dl or if your physician believes it is in your best interest to receive blood.

Study Team: Dr. Mansoor Qureshi. Kristina Wippler RN, BSN

The purpose of this study is to see if vagus nerve stimulation can improve the pumping function of the heart and reduce heart failure symptoms. Patients who have chronic heart failure have an imbalance in the nerves that stimulate the heart essentially keeping the heart in “overdrive” which can worsen the heart failure and symptoms over time. Previous studies have shown that stimulation of the vagus nerve with this special device may improve pumping function and symptoms related to heart failure.

To qualify for the study you must have:

• Symptomatic heart failure with an ejection fraction of less than or equal to 35%.
• Not received or intended for cardiac resynchronization therapy.

If you decide to participate you will be randomized, like flipping a coin. There are 2 chances out of 3 to be implanted with the device that includes a pulse generator (battery) and a wire. This is a computer controlled device much like a cardiac pacemaker. This sends signals to the heart and brain by stimulating the vagus nerve. You have a 1 out of 3 chance of being assigned to standard medical therapy. All patients will be seen in follow up by the study team at 4 weeks, 3, 6, 9, 12 and 16 months and every 4 months for up to 5 years.

Study Team: Dr. Ahmad Mizyed. Autumn Howe, RN, BSN.

This study is being done to evaluate the safety and effectiveness of renal denervation while you are still on your blood pressure medications. The purpose of the treatment (renal denervation) is to lower blood pressure. Therefore, the effectiveness of the study catheter together with the alcohol (Peregrine Kit) will be assessed by how well the treatment reduces your blood pressure.

To qualify for the study, you must:

• Be diagnosed with high blood pressure (hypertension)
• Be taking multiple medications to treat your high blood pressure

If you decide to participate, you will undergo certain screening procedures (MRA/CTA with contrast, ECG, physical examination, blood draws) to determine your eligibility for the study. The Screening Period maybe as short as a single day/visit, but no more than 8 weeks. Once your eligibility is confirmed, you will proceed to the Run-In Period (approximately 4 weeks prior to your scheduled procedure). During the Run-In Period (and 3 months after your procedure), you’ll be responsible for recording your blood pressure (using an automated blood pressure device that will be provided) twice a day and recording results in a subject diary. Clinic visits could also include questionnaires and surveys. On the day of the procedure, there is a 50% chance that you will be assigned to the Treatment Group (receiving the experimental renal denervation with the Peregrine Kits procedure), and a 50% chance that you will be assigned to the Control Group (not receiving renal denervation). After the procedure, you will enter the Follow-up Period which consists of at least 9 clinic visits. You will be in the study for approximately 40 months with a total of about 15-20 in-person clinic visits.

Study Team: Mansoor Qureshi, MD. Kristy Wippler, RN.

The purpose of this trial is to find out if a drug called empagliflozin, in addition to usual or standard care, will reduce the risk of heart failure and death in patients who had a heart attack (myocardial infarction). Empagliflozin has not been approved for your specific condition but it has been approved by the FDA for other uses. It has been approved by the FDA (brand name Jardiance®) to treat type 2 diabetes and to reduce the risk of cardiovascular death in adult patients with type 2 diabetes and established cardiovascular disease.

To qualify for the study you must have:

• Been told you have had a heart attack and hospitalized within the past 14 days.
• Be at high risk for heart failure or have an ejection fraction (pumping function of the heart) less than 45%.

If you decide to participate, you will be placed into one of two different study groups. You will be randomly assigned to receive either the placebo (no active drug) or empagliflozin the active drug. The decision about which group you will be in will be based on chance, like flipping a coin. This process is called randomization. You will not know which research drug/intervention you are receiving, and neither will your study doctor. You will complete a screening visit, randomization visit and a 2 week follow up visit with the study staff. At 6 months you are seen in the office. Thereafter, you will be contacted by the study staff every six months for up to two years.

Study Team: Dr. David Sutter. Megan Thompson, RN, BSN.

This study is testing an experimental drug called MK-0616 in people with high cardiovascular risk. “Experimental” means it has not been approved by the United States Food and Drug Administration (FDA). The main purpose of this study is to test safety of MK-0616, compared to placebo (A placebo looks like the study drug, but it has no active ingredients).

To qualify for the study:

• Taking certain medications to treat high cholesterol. The study doctor or study staff will discuss this with you.
• At risk for major cardiovascular events, such as heart attack and stroke.
• You are at least 18 years of age

If you decide to participate, you will be in the study about 4.5 years, with a maximum of about 6 years and visit the study site about 18 times. The study drug you get will depend on which group you are placed in. This study has 2 groups: Group 1 (will get MK-0616) and Group 2 (will get placebo). Other tests may occur at study visits, such as, blood draws and ECGs.

Study Team: Zakir Sahul, MD. Martha Bohn, RN

The study is being done to learn more about lepodisiran, a study drug that Lilly refers to as LY3819469, which is an experimental treatment for elevated lipoprotein (a) (Lp[a]); which is an increase in a type of fat in your blood that is not good for your health.

To qualify for the study:

• You have established cardiovascular disease, or you are at risk for a first cardiovascular event.

If you decide to participate, there will be a Screening Period (that can last up to 6 weeks) which will determine whether you continue to the Treatment Period. If you qualify for the Treatment Period, you will receive either the drug being studied, lepodisiran, or a placebo to compare how well they work. The study drug is an injection under your skin. You will receive the first 3 doses every 6 months and remaining doses every 12 months. This part of the study may last for about 4 years.

Study Team: Zakir Sahul, MD. Kristy Wippler, RN. Martha Bohn, RN. Meghan Stelzer, RN

The study is designed to identify the best way to treat pulmonary embolism, specifically when there is a large amount of clot, but the patient’s blood pressure is stable. While this condition is sometimes life-threatening, either of the treatments in this study work well to help people survive. Less is known about which treatment helps people do better in terms of breathing, heart function, and ability to exercise over time.

All patients with pulmonary embolism are treated with blood thinner medicines (anticoagulation). Sometimes, doctors will additionally do a procedure using a catheter to either remove the clot or give clot-dissolving medicines (catheter-directed therapy). It is not clear whether doing these procedures help patients who have a large amount of clot but who are more stable and at lower risk. This study, called PE-TRACT, compares blood thinners alone to blood thinners plus catheter-directed therapy in order to answer these questions and be able to provide patients with the most effective treatment. This is a national multi-site clinical trial and NYU Langone Health (NYULH) is the central coordinating center for the study.

Both treatment approaches are considered standard care and commonly used for patients with pulmonary embolism who are stable but who have large amounts of clot. The clot-dissolving medicine and devices used in catheter-directed therapy are cleared by the FDA for treatment of pulmonary embolism.

To qualify for the study, you must:

• you have blood clots in your lungs (called pulmonary embolism)

If you decide to participate, you will receive treatment for pulmonary embolism no matter which treatment group you are in. In the study, we will use a computer to assign you randomly to 1 of the 2 treatment groups. You will have a 50/50 (equal) chance of being in either treatment group. Group A will be treated with standard blood thinners and will have catheter-directed therapy to deliver a blood clot-dissolving medicine directly into the blood clot and/or suck out the blood clot. Group B will be treated with standard blood thinners alone.

Study Team: Hriday Shah, MD. Kristy Wippler, RN