araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Study of AKCEA-ANGPTL3-LRX (ISIS 703802) in Patients With Homozygous Familial Hypercholesterolemia (HoFH)

Summary: This is a single center, open-label study to evaluate the efficacy of AKCEA-ANGPTL3- LRX for reduction of low density lipoprotein cholesterol (LDL-C) levels in patients with Homozygous Familial Hypercholesterolemia (HoFH).


Eligibility: Inclusion Criteria:
  -  Body mass index (BMI) ≤ 35 kg/m2,
  -  Genetic confirmation of two mutant alleles at the LDLR, APOB, PCSK9, or LDLRAP1 gene locus OR an untreated LDL-C > 500 mg/dL (13 mmol/L) or treated LDL-C ≥ 300 mg/dL (2.59 mmol/L) together with either cutaneous or tendon xanthoma before age 10 years OR familial medical history of genetically confirmed heterozygous FH in both parents OR untreated elevated LDL-C and TC > 250 mg/dL consistent with the disease,
  -  Patients must be on stable LDL-C lowering agents or on regular apheresis
  Exclusion Criteria:
  -  Myocardial infarction, percutaneous transluminal coronary intervention, or coronary artery bypass graft surgery within 12 weeks prior to Screening, or cerebrovascular accident within 24 weeks prior to Screening.
  -  Diabetes mellitus if newly diagnosed or if HbA1c ≥ 9.0%

Relevance to patient case: definitely relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: NUtraceutical TReatment for hYpercholesterolemia in HIV-infected Patients

Summary: The effects of a nutraceutical combination (NC) containing low-dose monacolin K and berberine on lipid profile, proprotein convertase subtilisin/kexin type 9 (PCSK9), subclinical inflammation and arterial stiffness were investigated in human immunodeficiency virus (HIV)-infected patients receiving stable antiretroviral therapy (ART).

Detailed description: This is a crossover interventional study of 26 HIV-infected patients on stable ART with low density lipoprotein cholesterol (LDL-C) >100 mg/dL, not receiving any lipid-lowering treatment. After a 3-week lipid stabilization period with a standardized diet regimen, the effect of a 3-month oral NC containing red yeast rice-derived monacolin K 3 mg, berberine 500 mg, policosanol 10 mg, astaxanthin 0.5 mg, folic acid 0.2 mg and coenzyme Q10 2 mg vs no active treatment (noNC) was tested on plasma total cholesterol (TC), LDL-C, high density lipoprotein cholesterol (HDL-C), triglyceride, lipoprotein(a), PCSK9, high-sensitivity C-reactive protein (hsCRP) levels and aortic pulse wave velocity (aPWV).

Eligibility: Inclusion Criteria:
  -  LDL-C >100 mg/dL
  -  no history of cardiovascular disease
  -  stable ART for at least 6 months
  Exclusion Criteria:
  -  current or recent (≤6 months) treatment with lipid-lowering drugs
  -  chronic kidney disease [estimated glomerular filtration rate (GFR) <60 ml/min]
  -  liver impairment (AST and/or ALT >3 times upper limit of normal)
  -  current pregnancy
  -  opportunistic infections within the past 3 months,
  -  having received an organ transplant/immunosuppressive therapy

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Evolocumab in Acute Coronary Syndrome

Summary: Vascular and myocardial inflammation are significantly increased in Acute Coronary Syndrome (ACS) patients, are closely correlated to LDL-C levels, and are associated with these adverse consequences in the post-ACS patient population. Serum proprotein convertase subtilisin/kerin type 9 (PCSK9) levels are also increased in ACS, may raise LDL-C, and the investigators' pre-clinical studies indicate that PCSK9 is also a potent inducer of vascular inflammation. The addition of the PCSK9 antibody evolocumab, currently approved to lower LDL-C in certain patient populations, to current medical therapies would appear to be of particular benefit in an important subset of ACS patients, those with non-ST elevation myocardial infarction (NSTEMI) by markedly reducing LDL-C, stabilizing vulnerable plaque, and limiting inflammation-associated myocardial cell loss and resultant dysfunction.

Detailed description: In a placebo-controlled, randomized double blind trial, the addition of evolocumab to standard care in NSTEMI patients (1) decreases LDL-C during hospitalization and at 30 days, (2) decreases vascular/plaque and myocardial inflammation as assessed by Positron Emission Tomography (PET) scanning at 30 days, and improves (3) serum markers of endothelial function at hospital discharge and at 30 days, and (4) echocardiographic assessment of left ventricular function at 30 days and six months.
  This is the first PCSK9 inhibitor trial which examines these outcomes in the ACS patient population. It will provide valuable data on the extent and time course of LDL-C reduction as well as the impact of inhibition on inflammatory markers and on imaging assessment of vascular and myocardial inflammation, all of which may significantly impact important clinical outcomes in this high risk patient cohort.

Eligibility: Inclusion Criteria:
  -  Non ST segment elevation myocardial infarction
  -  Troponin I >/ 5.0 ng/dL
  -  Permission of attending physician
  Exclusion Criteria:
  -  ST elevation myocardial infarction
  -  Patients requiring invasive hemodynamic support
  -  Scheduled for cardiac surgery
  -  Current or prior treatment with a PCSK9 antibody
  -  Current participation in an intervention clinical trial
  -  Female of childbearing potential who has not used acceptable method(s) of birth control for at least one month prior to screening
  -  Contraindication to statin therapy
  -  Subject likely not able to complete protocol related visits or procedures
  -  Latex allergy
  -  History of hypersensitivity to any monoclonal antibody

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Study to Evaluate Efficacy and Safety of LIB003 in Patients on Lipid-Lowering Therapy Needing Additional LDL-C Reduction

Summary: Study to assess the LDL-C lowering efficacy of different doses of LIB003 administered every 4 weeks in subjects on stable statin and/or ezetimibe therapy

Detailed description: Randomized, Double-Blind, Placebo-Controlled, Phase 2 study to assess the LDL-C lowering efficacy at Week 12 of various doses of LIB003 administered subcutaneously (SC) every 4 weeks (Q4W) in patients with hypercholesterolemia on stable diet and oral LDL-C-lowering drug therapy.

Eligibility: Inclusion Criteria:
  1. Male or female, 18 years of age or older
  2. Elevated LDL-C on current lipid lowering therapy and; prior atherosclerotic cardiovascular disease (ASCVD) event or evidence of ASCVD or without ASCVD but at high risk for ASCVD based on AHA/ACC CVD risk calculator, or aged 40 years and older with diabetes and moderate- to high-intensity statin, or pre-treatment LDL-C 190 mg/dL or greater or heterozygous familial hypercholesterolemia (HeFH)
  3. Body mass index (BMI) between 18 and 40 kg/m2
  Exclusion Criteria:
  1. Females of childbearing potential not using or willing to use an effective form of contraception, or pregnant or breastfeeding, or who have a positive serum pregnancy test at screening
  2. Homozygous familial hypercholesterolemia
  3. LDL or plasma apheresis within 2 months; lomitapide or mipomersen within 12 months
  4. Uncontrolled cardiac arrhythmia, myocardial infarction, unstable angina, PCI, CABG, or stroke within 3 months prior to enrollment
  5. Uncontrolled cardiac arrhythmia, myocardial infarction, unstable angina, PCI, CABG, or stroke within 3 months prior to enrollment
  6. Newly diagnosed or poorly controlled (HbA1c >9%) type 2 diabetes
  7. Uncontrolled hypertension
  8. Moderate to severe renal insufficiency
  9. Elevated liver function test at screening
  10. Uncontrolled cardiac arrhythmia or prolonged QT on EKG
  11. A history of prescription drug abuse, illicit drug use, or alcohol abuse

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Investigating the Effects of Lipid-therapy Intensification With Alirocumab on Endothelial Function, Carotid Arteries, Lipoprotein Particle Subfractions, Inflammation and Post-prandial Lipemia

Summary: A prospective, open-label, pilot study with 24 cardiovascular high risk patients (N=24) having insufficient Low density lipoprotein cholesterin (LDL-C) reduction despite standard of care lipid-modifying therapies (LMTs), to evaluate the effects of potent lipid-therapy intensification via the recently approved monoclonal, human anti-PCSK9 antibody Alirocumab on endothelial function, inflammation, lipoprotein particle subfractions, carotid arteries and post-prandial lipemia in clinical routine at the Medical University of Graz.


Eligibility: Inclusion Criteria:
  1. Patient scheduled for treatment with Alirocumab in clinical routine (after approval of cost coverage by insurance company)
  2. No previous treatment with PCSK9 antibodies
  3. Signed informed consent form
  Exclusion Criteria:
  1. Age of < 18 years
  2. Pregnancy (pregnancy test at screening visit)
  3. Breast-feeding
  4. Impossibility to perform magnetic resonance imaging of the carotid artery (claustrophobia, carotid stent)

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Study to Assess Efficacy of Besifovir and L-carnitine in Chronic Hepatitis B Patients With Nonalcoholic Fatty Liver

Summary: Pilot study to assess the antiviral activity and safety of Besifovir dipivoxil 150mg and L-carnitine 660mg compared to Tenofovir Alafenamide 25mg in chronic hepatitis B patients with Nonalcoholic fatty liver


Eligibility: Inclusion Criteria:
  -  20 years of age and older, Male or female patients
  -  Chronic hepatitis B patients with Nonalcoholic fatty liver
  -  Patients who use oral anti-diabetic drug or drugs for hyperlipemia without any change in drug dosage within 2 month before screening visit
  -  Patients who have been explained about the trial and agreed to the consent
  -  Patients who agree with the approved method of contraception during the clinical trial
  Exclusion Criteria:
  -  Patients with hepatitis C virus, hepatitis D virus or human immunodeficiency virus
  -  Patients who has a history of liver transplantation or Child-Pugh score >=8
  -  Alpha-fetoprotein (AFP) > 50 ng/mL or Hepatocellular Carcinoma (HCC) patients
  -  Patients who have taken Besifovir or Vemlidy
  -  Among the patients treated with immunosuppressive drug within 6 months before screening, suspected case of the declined immunity in the opinion of the investigator
  -  Chronic alcoholism (Significant alcohol consumption: male > 210 g/week, female> 140 g/week)
  -  Patients who take drugs that can cause hepatic steatosis
  -  Patient diagnosed with a malignant tumor within 5 years before screening or relapsed patient
  -  Patients with uncontrolled diabetes mellitus (HbA1c > 9%) or using insulin
  -  Patients who participate in other clinical trials or is supposed to do so during the study period
  -  Pregnant or breast-feeding women or women who have plan to be pregnant.
  -  Patients with a history of hypersensitivity to the test drug or the components of the test drug
  -  Patients with moderate or severe renal impairment
  -  Patients with genetic problems such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
  -  History within the past one years or presence of drug abuse or alcoholism.
  -  Patient has serious disease judged by investigator such as heart failure, renal failure, and pancreatitis
  -  Patient has liver diseases except chronic hepatitis B (i.e. hematochromatosis, alcoholic liver disease, nonalcoholic fatty liver disease, alpha-1 antitrypsin deficiency etc.)
  -  Patient has history of organ transplantation
  -  Patient concerned about the decline in daily activity or not able to understand the objectives and methods due to the psychiatric problems
  -  Patients who are considered to be unacceptable in this study under the opinion of the investigator.

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Return of Actionable Variants Empirical Study

Summary: This is a genomic implementation project with ancillary studies to understand the impact on patients' health and well-being of returning genomic results to them and depositing those results in the medical record.

Detailed description: Study participant DNA samples will be sequenced for 109 genes of interest along with genotyping of select polymorphisms. Genetic tests will be performed in a Clinical Laboratory Improvement Amendments (CLIA) certified lab (Baylor Human Genome Sequencing Laboratory). Selected results (pathogenic/likely pathogenic) will be returned to participants by a genetic counselor and deposited into the Electronic Health Record (EHR).

Eligibility: Inclusion Criteria:
  -  Moderate to Severe Hypercholesterolemia, elevated triglycerides, or colon polyps
  -  Resident of southeast Minnesota area
  -  Able to provide informed consent
  -  Current participant in the Mayo Clinic Biobank (08-007049, Cerhan PI), the Vascular Disease Biorepository (08-008355, Kullo PI), or the Study of the Genetic Determinants of Peripheral Artery Disease (PAD) (06-002911, Kullo PI) with blood derived DNA available
  Exclusion Criteria:
  -  Pregnant women will be allowed to enroll in the study. This is not an interventional study and there will be no risk to the mother or neonate. Other vulnerable study populations will be excluded.

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Effects of Acute, Rapid Lowering of LDL Cholesterol With Alirocumab in Patients With STEMI Undergoing Primary PCI

Summary: A randomized, double-blind, placebo controlled parallel group clinical trial evaluating the effects of acute treatment with a PCSK9 inhibitor (alirocumab) versus placebo on low-density lipoprotein (LDL) in 100 high-risk patients presenting with STEMI and referred for primary PCI.
  The objective is to determine the effect of acute, rapid lowering of LDL cholesterol with alirocumab added to high dose statin therapy in patients with STEMI undergoing primary PCI. The hypothesis is that, in patients with STEMI undergoing primary PCI, rapid lowering of LDL cholesterol with a PCSK9 Inhibitor (alirocumab) initiated in the acute setting pre-PCI, will favourably affect LDL cholesterol concentrations compared with placebo.


Eligibility: Inclusion Criteria:
  -  Patients presenting with STEMI defined as both of the following: a) Symptoms of myocardial ischemia lasting for ≥ 30 minutes, and b) Definite ECG changes indicating STEMI: ST elevation of greater than 0.1 mV in two contiguous limb leads or 0.2 mV in two contiguous precordial leads.
  -  Referred for primary PCI for presenting symptoms.
  -  Randomized within 12 hours of symptom onset and prior to diagnostic angiography.
  Exclusion Criteria:
  -  Age ≤18 years.
  -  Pregnancy or breastfeeding.
  -  Current or planned treatment with a PCSK9 inhibitor.
  -  Allergy or contra-indication to a PCSK9 inhibitor.
  -  Killip class ≥2.
  -  Known Creatinine clearance <30mL/min.
  -  Suspected takotsubo / stress-induced cardiomyopathy or acute pericarditis.
  -  Any other medical, geographic, or social factor making study participation impractical or precluding follow-up.

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Pharmacokinetic Boosting of Osimertinib

Summary: The main objective of this study is to evaluate if systemic exposure of osimertinib (i.e. AUC) is increased when osimertinib is co-administered with cobicistat in patients with relatively low plasma trough concentration while receiving the standard osimertinib dose.

Detailed description: Osimertinib is a new targeted agent registered for the treatment of patients with EGFR-mutated NSCLC. However, the costs of those new treatments are extremely high. Osimertinib is mainly metabolized by CYP3A4, and partially by CYP3A5. Combination of osimertinib with a strong CYP3A4-inhibitor may result in a smaller first-pass effect and a decreased clearance of osimertinib, thereby increasing the exposure to osimertinib.
  Cobicistat is a strong CYP3A4-inhibitor, this mechanism may be used to boost osimertinib, as is done for other drugs, mainly drugs used to treat HIV-infected patients.
  Using this personalized treatment approach and combining the concepts of therapeutic drug monitoring (TDM) and pharmacokinetic boosting, osimertinib therapy could become much more cost-effective. By reducing the necessary dose of osimertinib, this strategy may ultimately result in a significant reduction in drug costs, as the additional expenditure for the CYP3A4 inhibitor and blood sample analysis are negligible compared to the price of osimertinib.

Eligibility: Inclusion Criteria:
  -  Patients with EGFR-mutated NSCLC receiving standard treatment with osimertinib for at least two months, without any signs of disease progression.
  -  Stable disease, partial or complete response on the most-recent tumour-response evaluation.
  -  Age ≥ 18 years
  -  WHO performance status ≤ 2.
  -  Able and willing to give written informed consent.
  -  Able and willing to undergo blood sampling for pharmacokinetic analysis.
  -  Patients with osimertinib plasma trough concentration below 135 ng/mL. Plasma trough concentration of osimertinib will be determined in another study (METC MUMC: 2018-0800).
  Exclusion Criteria:
  -  Any concurrent medication that is known to strongly inhibit or induce CYP3A4.
  -  Any concurrent medication that is primarily metabolized by CYP3A4 with a narrow therapeutic window.
  -  Impairment of gastrointestinal function that may alter the absorption of osimertinib or cobicistat (e.g. ulcerative disease, uncontrolled nausea or vomiting, malabsorption syndrome, small bowel resection).
  -  Refusing to refrain from consuming CYP3A4 influencing products, e.g. grapefruit(juice), St. John's wort.
  -  Pregnancy or breast feeding
  -  Child-Pugh score class C, chronic liver disease.

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Evolocumab for PCSK9 Lowering in Early Acute Sepsis (The PLEASe Study)

Summary: This study evaluates using evolocumab, a currently approved and marketed biologic drug, in a novel way. Patients who present to the emergency room or intensive care unit (ICU) with severe infection are eligible. Either the patient or their designated decision maker will be approached for consent. If they choose to participate they will be given either a single dose of evolocumab, a higher single dose of evolocumab,or a single dose of placebo. Participants will be followed during their stay in the ICU and will receive follow up phone calls at Day 28 and 90.

Detailed description: Evolocumab is currently approved and marketed in USA and Canada for lowering cholesterol levels. Evolocumab is an anti-PSCK9 monoclonal antibody, and functions by binding PSCK9 (an inhibitor of LDL removal) and blocking its function. Evidence suggests that since evolocumab increases the removal rate of low-density lipoproteins from the body, it might also help increase the removal of bacterial components that are attached to circulating lipids during sepsis. Quickly removing these bacterial components could prevent a strong and rapid immune response that often leads to organ failure and death in sepsis patients.

Eligibility: Inclusion Criteria:
  -  Signed informed consent
  -  At least 19 years of age
  -  Known or suspected infection
  -  AND one or more of the following organ dysfunctions judged due to sepsis:
  1. Cardiovascular- refractory hypotension (a systolic blood pressure (SBP) < 90 mm Hg or mean arterial pressure (MAP) < 60 mm Hg despite an IV fluid challenge of at least 30 ml/kg fluids), or use of vasopressor(s) to maintain SAP > 90 mm Hg or MAP > 60 mm Hg, or;
  2. Respiratory: PaO2/FiO2 < 300 or PaO2/FiO2 < 200 if lung is the only organ dysfunction or SaO2:FiO2 150
  Exclusion Criteria:
  -  Known pregnancy
  -  Underlying severe congestive heart failure (New York Heart Association (NYHA) IV), severe COPD (need for chronic oxygen or mechanical ventilation), severe liver disease (Child-Pugh Class C), cancer requiring chemotherapy, or transplantation (bone marrow, heart, lung, liver, pancreas, or small bowel) in the past 6 months or likely within the next 6 months
  -  Previous episode of sepsis during that hospital admission
  -  Absolute Neutrophil Count < 500/mm³
  -  CD4 count < 50/mm³
  -  Treating physician deems aggressive care unsuitable (i.e. no commitment to active care)
  -  Participation in another interventional drug study within previous 1 month
  -  Allergic to the study drug or any of its components
  -  Lactation
  -  Have signed a Do No Resuscitate (DNR) Form

Relevance to patient case: not relevant